Filler Comparison
Restylane
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL
Indication
Restylane is indicated for mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds.
How Supplied
Restylane is supplied in a disposable glass syringe with a luer-lock fitting. Restylane is co-packed with sterilized needle(s) as indicated on the carton, either 30 G x ½" or 29 G x ½". A patient record label is a part of the syringe label. Remove it by pulling the flap marked with three small arrows. This label is to be attached to patient records to ensure traceability of the product. The contents of the syringe are sterile. The volume in each syringe and needle gauge is as stated on the syringe label and on the carton.
Self Life and Storage
Restylane must be used prior to the expiration date printed on the package.
Store at a temperature of up to 25° C (77° F). Do not freeze. Protect from sunlight. Refrigeration is not required.
Do not resterilize Restylane as this may damage or alter the product.
Do not use if the package is damaged or if expiry date or lot number is missing or illegible.
Immediately return the damaged product to Galderma Laboratories, L.P
Contraindications
- Restylane is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- Restylane is contraindicated for patients with bleeding disorders.
- Restylane is contraindicated for implantation in anatomical spaces other than the dermis or submucosal implantation for lip augmentation.
Warnings
- Defer use of Restylane at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
- Injection site reactions (such as swelling, redness, tenderness, pain, bruising or itching) to Restylane have been observed as consisting mainly of short-term minor or moderate inflammatory symptoms starting early after treatment and with less than 7 days duration in the nasolabial folds and less than 14 days duration in the lips. Rare post-market reports of immediate post-injection reactions included extreme swelling of lips, the whole face and symptoms of hypersensitivity such as anaphylactic shock.
- Restylane must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar area. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area. 2 (32)
- Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
- Injections of greater than 1.5 mL per lip (upper or lower) per treatment session significantly increases the occurrence of moderate to severe injection site reactions. If a volume of more than 3 mL is needed to achieve optimal correction, a follow-up treatment session is recommended.
- In a meta-analysis of all Restylane Premarket Approval Studies (that included 42 patients under the age of 36 and 820 patients over the age of 35), the incidence of swelling was higher in younger patients (28%) compared to older patients (18%) and incidence of contusion was higher in older patients (28%) compared to younger patients (14%). The majority of these events were mild in severity.
Precautions
- Restylane is packaged for single patient use. Do not resterilize. Do not use if package is opened or damaged.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Based on U.S. clinical studies, patients should be limited to 6.0 mL per patient per treatment in wrinkles and folds such as the nasolabial folds and to 1.5 mL per lip per treatment. The safety of injecting greater amounts has not been established.
- The safety or effectiveness of Restylane for the treatment of anatomic regions other than nasolabial folds or lips has not been established in controlled clinical studies.
- As with all transcutaneous procedures, Restylane implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety of Restylane for use during pregnancy, in breastfeeding females or in patients under 18 years has not been established.
- The safety and efficacy of Restylane for lip augmentation has not been established in patients under the age of 21 years.
- Formation of keloids may occur after dermal filler injections including Restylane. Keloid formation was not observed in studies involving 430 patients (including 151 African-Americans and 37 other patients of Fitzpatrick Skin Types IV, V and VI). For additional information please refer to Studies MA-1400-02, MA-1400-01, and 31GE0003 in the Clinical Trials Section.
- Restylane injection may cause hyperpigmentation at the injection site. In a clinical study (MA1400-01) of 150 subjects with pigmented skin (of African-American heritage and Fitzpatrick Skin Types IV, V, and VI), the incidence of post-inflammatory hyperpigmentation was 9% (14/150). 50% of these events lasted up to six weeks after initial implantation.
- The safety profile for Restylane lip augmentation in persons of color is based upon information from 38 and 3 subjects with Fitzpatrick Skin Types IV and V, respectively. Within this population, the incidence of adverse events was similar to the overall study population, with the exception that swelling occurred more frequently in persons of color.
- Injection of Restylane in patients with pre-existing tendency toward edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up.
- Injection of Restylane too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable lumps.
- Restylane should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at Restylane injection sites. Restylane should be used with caution in patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the preceding 3 weeks.
- Avoid injecting Restylane into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane into an area where an implant other than hyaluronic acid has been placed.
- The safety of Restylane with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane is administered before the skin has healed completely after such a procedure.
- Injection of Restylane into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Individual variation and treatment area may affect the bio-degradation of Restylane, in rare cases product remnants has been detected in tissue when the clinical effect has returned to baseline.
- Restylane is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Galderma Laboratories, L.P. at 1-855-425-8722.
- Glass is subject to breakage under a variety of unavoidable conditions. Care should be taken with the handling of the glass syringe and with disposing of broken glass to avoid laceration or other injury.
- After use, syringes and needles should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
- Restylane should not be mixed with other products before implantation of the device.
Adverse Experiences
There were six U.S. studies that reported adverse experiences. Four of the six studies were conducted in support of the indication of mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds, and two of the six studies were conducted in support of the indication of submucosal implantation for lip augmentation. Studies conducted in moderate to severe facial wrinkles and folds, such as nasolabial folds Three U.S. studies (i.e., Study 31GE0003, MA-1400-01, and Study MA-1400-02) involved 430 patients at 33 centers. In study 31GE0003, 138 patients at 6 centers received Restylane injections in 1 side of the face and a bovine collagen dermal filler (Zyplast®) in the other side of the face. In Study MA-1400-01, 150 patients were injected with Restylane on one side of the face and Perlane® on the other side of the face. In study MA-1400-02, 283 patients were randomized to receive either Restylane or Perlane injection on both sides of the face. The adverse outcomes reported in patient diaries during 14 days after treatment in these studies are presented in Tables 1–6. The physician diagnosed adverse events identified in studies MA-1400-01 and MA-1400-02 at 72 hours after injection are presented in Table 7. Table 8 presents all investigator-identified adverse experiences recorded at study visits 2 weeks or more after injection in studies MA-1400-01, MA-1400-02, and 31GE0003. In the fourth U.S. study (MA-004-03) involving 75 patients at 3 centers, adverse events reported by Restylane patients are presented in Table 9. Patients in the study received Restylane injections in both nasolabial folds at baseline, a second treatment in one nasolabial fold at 4.5 months and in the contralateral nasolabial fold at 9 months.
Table 7 shows the number of adverse experiences identified by investigators at 72 hours after injection for Studies MA-1400‑01 and MA-1400-02. Some patients had multiple adverse experiences or had the same adverse experience at multiple injection sites. No adverse experiences were of severe intensity.
Table 8 presents the number of patients and per patient incidence of all adverse experiences identified by investigators at visits occurring two or more weeks after injection.
In a clinical study (31GE0003) in which safety was followed for 12 months with repeat administration of Restylane at six to nine months following the initial correction, the incidence and severity of adverse experiences were similar in nature and duration to those recorded during the initial treatment sessions. In all three studies, investigators reported the following local and systemic events that were judged unrelated to treatment and occurred at an overall incidence of less than 2%, i.e., acne; arthralgia; tooth disorders (e.g., pain, infection, abscess, fracture); dermatitis (e.g., rosacea, unspecified, contact, impetigo, herpetic); unrelated injection site reactions (e.g., desquamation, rash, anesthesia); facial palsy with co-administration of botulinum toxin; headache/migraine; nausea (with or without
vomiting); syncope; gastroenteritis; upper respiratory or influenza-like illness; bronchitis; sinusitis; pharyngitis; otitis; viral infection; cystitis; diverticulitis; injuries; lacerations; back pain; rheumatoid arthritis; and various medical conditions such as chest pain, depression, pneumonia, renal stones, urinary incontinence, and uterine fibroids.
Table 9 presents the number of patients and per patient incidence and severity of injection site adverse events identified by the investigator. Two subjects had adverse events that were severe, one subject with bilateral facial bruising and one subject with infection at the injection site. These events were considered probably or possibly related and both subjects had their events resolve in approximately 3 weeks. Studies conducted for submucosal implantation for lip augmentation In the U.S. pivotal study (MA-1300-15) involving 180 subjects at 12 centers, the adverse outcomes reported in subject diaries are presented in Tables 10 and 11. Physician reported treatment emergent adverse events are presented in Table 12. At baseline, subjects were randomized to receive Restylane injections in the lips or no treatment (control group). At 6 months, all subjects were eligible to receive treatment or re-treatment in the lips with Restylane. Of the 180 subjects enrolled in the study, 172 subjects received their first treatment with Restylane at either baseline/Day 0 or at 6 months, and 93 subjects received a second treatment at 6 months. There were 8 subjects enrolled in the study that were never treated. The number of events and subjects reporting TEAEs decreased between the first and second treatments. 87% of subjects receiving their first treatment reported a total of 795 TEAEs while 65% of subjects that received a second treatment reported a total of 267 TEAEs. Furthermore, an overwhelming majority of these TEAEs were mild in intensity (672/795, 85%; and 264/267, 99%; first and second treatment respectively), and were transient in nature, resolving in approximately 15 days or less. The study results showed injection of greater than 1.5 mL per lip (upper or lower), per treatment session increased the occurrence of the total of moderate and severe injection site reactions. The incidence was 43% (33/76) for subjects receiving more than 3.0 mL of Restylane and 21% (20/96) for subjects receiving less than 3.0 mL of Restylane in a single treatment session. When optimal correction requires greater than 1.5 mL per upper or lower lip, subsequent treatment using additional product is recommended. 97% of the subjects reported at least one event of swelling, redness, tenderness, or pain in their
diaries. These were mainly short-term events, which occurred immediately after treatment and resolved within 14 days. 15% of the subjects reported adverse events (typically swelling and tenderness) that lasted longer than 15 days in their diary. 46% of subjects reported at least one event
as “affecting their daily activity” or “disabling.” Additional safety assessments in the study included lip texture, firmness, symmetry, movement, function, sensation, mass formation, and product palpability, which were evaluated as appropriate at the screening visits and at follow-up visits.The majority of texture and firmness assessments showed mild abnormalities and lasted for less than 4 weeks. Sixteen subjects reported severe asymmetry (difference > 2mm) post-treatment, which all resolved within 4 weeks. GAIS assessments by these 16 subjects were rated as at least improved during those visits. Assessments made by the trained health care provider showed 92% of subjects had product palpability at week 8, and 61% at week 24. The majority of palpations were rated as “expected reel.” 3% of the subjects reported “unexpected feel” during the study, all of which were resolved
with massaging. One subject reported one mass formation (mucocele) during the study. The mucocele was drained and resolved by the next visit. All other lip safety assessments showed no remarkable findings. In the pilot study MA-1300-13K, 20 subjects were enrolled at 1 center and received Restylane for lip augmentation. Subjects were followed up through 24 weeks. Seven adverse events were reported. Two of the seven events, which were mild bruising, were related to injection procedure.
The adverse outcomes reported in subject diaries are presented in Table 13.
Table 12 presents commonly reported (≥ 5%) treatment emergent adverse events (TEAEs) by treatment group. For study MA-1300-13K, seven treatment emergent adverse events were experienced by four subjects. Two of these events, mild bruising, were considered related to treatment.
Directions For Assembly
For safe use of Restylane, it is important that the needle is properly assembled. Improper assembly may result in separation of the needle and syringe during implantation.
Syringe with white cap:
Use your thumb and forefinger to hold firmly around both the syringe barrel and the luer-lock adapter part (C) of the closure system. With your other hand, take hold of the white cap (A) at the end of the closure system and gently tilt back and forth carefully until cap disconnects and can be pulled off (seal will be broken).
Do not rotate.
Do not touch the syringe tip (B) to keep it sterile.
Syringe with transparent cap:
Unscrew the tip cap of the syringe carefully.
Assembly Of Needle To Syringe
Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the luer-lock adapter (C). Grasp the needle shield with the other hand. To facilitate proper assembly, both push and rotate firmly clockwise. Make sure the needle is screwed on all the way so that the needle shield touches the luer-lock adapter (C). To remove the needle shield, hold the syringe and the luerlock adapter. With your other hand hold the needle shield and pull straight out. Do not rotate.
Pre-Treatment Guidlines
Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John’s Wort, or high doses of Vitamin E supplements. These agents may increase bruising and bleeding at the injection site.
Treatment Procedures
1. It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the Restylane treatment. Advise the patient of the necessary precautions before commencing the procedure.
2. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block.
3. The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
4. Sterile gloves are recommended while injecting Restylane.
5. Before injecting, press rod carefully until a small droplet is visible at the tip of the needle.
6. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify that the needle is not intravascular.
7. Restylane is administered using a thin gauge needle (30 G x ½" or 29 G x ½"). The needle is inserted at an approximate angle of 30° parallel to the length of the wrinkle, fold, or lip. For the nasolabial folds, Restylane should be injected into the mid-to-deep dermis. For lip augmentation, Restylane should be injected into the submucosal layer; care should be taken to avoid intramuscular injection. If Restylane is injected too superficially this may result in visible lumps and/or bluish discoloration.
8. Inject Restylane applying even pressure on the plunger rod. Do not apply excessive pressure to the syringe at any time. If resistance is encountered, the needle should be partially withdrawn and repositioned, or fully withdrawn, checked for function and replaced if needed. It is important that the injection is stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
9. Only correct to 100% of the desired volume effect. Do not overcorrect. With cutaneous deformities the best results are obtained if the defect can be manually stretched to the point where it is eliminated. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue and the injection technique.
10. Typical usage for each treatment session is specific to the site as well as wrinkle severity. In a prospective study of midface wrinkle correction, the median total dose was 3.0 mL. Based on U.S. clinical studies, the maximum recommended dose per treatment is 6.0 mL for the nasolabial folds and 1.5 mL per lip per treatment.
Injection Technique
1. Restylane can be injected by a number of different techniques that depend on the treating physician’s experience and preference, and patient characteristics.
2. Serial puncture (A) involves multiple, closely spaced injections along wrinkles or folds. Although serial puncture allows precise placement of the filler, it produces multiple puncture wounds that may be undesirable to some patients.
3. Linear threading (includes retrograde and antegrade) (B) is accomplished by fully inserting the needle into the middle of the wrinkle or fold and injecting the filler along the track as a “thread.” Although threading is most commonly practiced after the needle has been fully inserted and is being withdrawn, it can also be performed while advancing the needle (“pushahead” technique). To enhance the vermillion of the lip, the retrograde linear threading technique is the most advisable.
4. Serial threading is a technique that utilizes elements of both approaches.
5. Cross-hatching (C) consists of a series of parallel linear threads injected at intervals of five to ten mm followed by a new series of threads injected at right angles to the first set to form a grid. This technique is particularly useful in facial contouring when coverage of the treatment region needs to be maximized.
A. Serial Puncture
B. Linear Threading (includes retrograde and antegrade)
C. Cross-hatching
6. Note! The correct injection technique is crucial for the final result of the treatment. Dissection of the sub-epidermal plane with lateral movement of the needle, rapid flows (>0.3 mL/min), rapid injection or high volumes may result in an increase in short-term episodes of bruising, swelling, redness, pain, or tenderness at the injection site.
7. It is recommended to change needle for each new treatment site.
8. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area firmly between your fingers, or against the underlying area to obtain optimal results.
9. If so called “blanching” is observed, i.e., the overlying skin turns a whitish color, the injection should be stopped immediately and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with the American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection1.
10. If the wrinkle or lips need further treatment, the same procedure should be repeated until a satisfactory result is obtained. Additional treatment with Restylane may be necessary to achieve the desired correction.
11. If the treated area is swollen directly after the injection, an ice pack can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
12. Patients may have mild to moderate injection site reactions, which typically resolve in less than 7 days in the nasolabial folds and less than 14 days in the lip.
Sterile Needles
- Follow national, local or institutional guidelines for use and disposal of medical sharp devices.Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided.
- Discard unshielded needles in approved sharps collectors.
- Restylane is provided with a needle that does not contain engineered injury protection. Administration of Restylane requires direct visualization and complete and gradual insertion ofthe needle making engineered protections infeasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
Q What is Restylane®?
A Restylane® is a crystal clear injectable gel composed of hyaluronic acid, a natural substance that already exists in the body. Restylane® is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. Restylane® is nonanimal based and free from animal protein. Allergy pretesting is not necessary.
Q How does Restylane® work?
A Restylane® is injected into the skin with an ultrafine needle to plump the skin to smoothaway wrinkles and folds such as the lines from your nose to the corners of your mouth (nasolabial folds) or your lips.
Q How long does Restylane® last?
A Restylane® effects generally last six months and gradually disappears from the body. If you are treated again at 4 ½ or 9 months after your first treatment, Restylane® can last up to 18 months.
Q Has Restylane® been studied?
A Restylane® has been studied in facial wrinkles and folds, such as the lines from your nose to the corners of your mouth (nasolabial folds), and in the lips. The studies show that Restylane® effects generally last at least six months and gradually disappears from the body. If you are treated again at 4 ½ or 9 months after your first treatment, Restylane® can last up to 18 months.
Safety
Q Who should not use Restylane® (Contraindications)?
A Safety has not been established for use in people who are:
- Pregnant
- Breast feeding
- Wishing to be pregnant
- Under 18 years or over 65 years
- Highly allergic (for example: gram positive bacteria)
- Prone to bleeding disorders
Q What are some warnings to consider?
A The use of Restylane® at sites with skin sores, pimples, rashes, hives, cysts, or infections should be postponed until healing is complete. Use of Restylane® in these instances could delay healing or make your skin problems worse. You may experience skin discoloration (bruising), swelling, redness, tenderness, pain, itching, or small lumps in the area where you are injected. If any of these events occur, the majority usually last less than seven days. If any symptom lasts longer than two weeks, call the doctor who administered the Restylane® injection. Red or swollen small bumps (inflammatory papules) may rarely occur. You may need antibiotics to treat them.
Q What are some potential risks you may encounter?
A As with all procedures like this, the injection of Restylane® carries a risk of infection and formation of scar tissue. The safety and effectiveness of Restylane® has not been established in pregnant, or nursing mothers, and in patients under 18 or over 65 years of age. Restylane® use in nursing could harm you or the nursing child. The use of Restylane® in African-American patients can result in darkening of skin color (hyperpigmentation ), which may take several weeks to correct. If you have previously had facial cold sores, an injection can cause them to come back. The safety of Restylane® used with other skin therapies such as laser, mechanical or chemical peeling, and hair removal has not been established. The use of Restylane® with these skin therapies may lead to other side effects such as inflammation. You should avoid exposing the area(s) treated with Restylane® to excessive sun or UV lamps, and extreme heat and cold until any redness or swelling has disappeared. Clinical volunteers keeping diaries reported the following short-lived events: Bruising, redness, swelling, pain (includes burning), tenderness, and itching. Most of these symptoms were considered tolerable and resolved in less than a week.
Q What are the major side effects?
A Rarely, the doctor may inadvertently inject the product into a blood vessel, which can cause injury to the blood supply and damage to the skin. In rare cases injection into a blood vessel could also result in vision changes (including blindness) and stroke. Rarely, a few people have developed infections that must be treated with antibiotics or other treatment. Infection may be hard to treat, but will generally go away when the gel is absorbed.
Q What should patients do prior to treatment?
A Restylane® requires no pretesting, but you should take a few precautions before being treated. Avoid using St. John’s Wort, high doses of Vitamin E supplements, aspirin, and other non-steroidal anti-inflammatory medications, such as ibuprofen prior to treatment, because these may increase bruising or bleeding at the injection site. Also, if you have previously suffered from facial cold sores, discuss this with your physician. He or she may consider prescribing a medication to minimize recurrences.
Q Do the injections hurt?
A Restylane® is injected directly into the skin in tiny amounts by an ultrafine needle. To help maximize your comfort, you should discuss the use of numbing medicines with your doctor before treatment.
Q How much does Restylane® treatment cost?
A Restylane® is a customized procedure based on your specific needs, so the cost will vary from patient to patient. In general, the cost of Restylane® is similar to the cost of similar procedures. Please ask your doctor to give you an estimate of the cost.
Troubleshooting
Q What should I call my doctor about after the treatment?
A Most side effects like bruising, swelling, pain, tenderness, redness, and itching will usually go away within a week. Call your doctor if you have persistent problems beyond 14 days.
Blisters or skin sores that recur may signal the presence of a herpes infection that must be treated. You can develop an infection that should be treated with antibiotics. If you experience redness, tenderness, and pain that does not go away you should call your doctor. Seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure (http://www.nlm.nih.gov/medlineplus/stroke.html).
Administration
Q What is the dose of Restylane®? A The amount used depends on your face and what you would like to have treated. The average patient who has all of the severe wrinkles around the mouth or lips corrected will use less than half a tablespoon.
Post Marketing Surveillance
Q Have there been adverse events reported through post market surveillance?
A The adverse events received from post-marketing surveillance (voluntary reporting and published literature) for Restylane with and without lidocaine in the U.S. and other countries most commonly included: reports of transient swelling (edema) and inflammatory reactions with – immediate onset or delayed onset, up to several weeks after treatment. The following events were also reported in decreasing order of frequency:
- Lumps or bumps (mass formation), hardening (induration)
- Short duration of effect
- Skin redness (erythema)
- Pain or tenderness
- Bruising (hematoma)
- Small bumps (papules or nodules)
- Presumptive bacterial infections and pus (abscess formation)
- Skin discoloration (hyperpigmentation)
- Injection site reactions including burning sensation, warmth, irritation
- Restricted blood flow leading to the death of skin (ischemia and necrosis)
- Allergic reaction (hypersensitivity), rapid swelling (angioedema)
- Eye disorders such as dry eye, eye irritation, eye pain, eye swelling, increased flow of tears (increased lacrimation), eyelid drooping (eyelid ptosis)
- Visual disturbance including blurred vision, reduced vision, and blindness
- Reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia), tremor, and facial nerve paralysis
- Itching (pruritus)
- Leakage of product from implant site (extrusion of device)
- Scarring
- Small area of inflammation in tissue (granuloma)
- Device dislocation
- Symptoms of reactivation of herpes infection
- Rash
- Blisters/vesicles
- Spider veins/broken capillaries (telangiectasia)
- Abnormal connection between two body parts (fistula)
- Leakage from implant site (effusion/discharge)
- Acne
- Skin inflammation (dermatitis)
- Hives (urticaria)
- Muscle disorders such as muscle twitching and muscle weakness
- Encapsulation of gel in the tissue
- Fungal infection of the skin (dermaphytosis)
- Other dermatological events including dry skin, skin wrinkling, peeling of skin and localized hair loss (alopecia)
- Non-dermatological events including headache, discomfort (malaise), fever, dizziness, sinus infection, shortness of breath (dyspnea), feeling tired (fatigue), influenza like illness, insomnia, nausea and anxiety
The treatments of these events included ice, massage, warm compress, nitroglycerine paste, drugs to reduce inflammation (corticosteroids), antibiotics, medicine that prevents the clotting of blood (anticoagulants), drugs to relieve allergy symptoms (antihistamines), drugs to relieve pain (analgesics), antiviral agents, medicine to relieve the body of excess fluid (diuretic agents), surgical procedure (incision and drainage) or a medicine used to help breakdown hyaluronic acid in the body (hyaluronidase). The most commonly reported serious adverse events were infection/pocket of pus (abscess), restricted blood flow leading to the death of skin (ischemia/necrosis), scarring, vision loss, allergic reactions (hypersensitivity), scarring, and areas of inflammation in tissue (granuloma) including cases of hardening (mass/induration). Other serious events included common related symptoms such as; swelling, pain/tenderness, skin redness (erythema), reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia), inflammation, bruising and skin discoloration. Serious infections/pocket of pus (abscess) were reported with a time to onset ranging from one day to 6 months following the injection. The infections usually resolved after two days up to a few months and most of the patients had recovered or were recovering at the time of last contact. The treatments included antibiotics, drugs to relieve pain (analgesics), drugs to reduce inflammation (corticosteroids) and hyaluronidase (a medicine to help break down the Restylane so that it is more easily absorbed).Serious small area of inflammation in tissue (granuloma), including hardening, were reported with a time to onset ranging from a month up to a year or longer. The outcomes were mostly recovered or recovering at the time of last contact. Treatment included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines,) antibiotics, drugs to reduce inflammation (corticosteroids) and surgical removal (excisions). Incisions to examine tissue (biopsies) have been taken in some cases, but the majority of cases are non-biopsy confirmed. Serious allergic reactions (hypersensitivity) were reported in most cases with a time to onset ranging from immediately to few weeks post injection. Most of the events were recovered or recovering at the time of last contact. The treatments included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines), antibiotics, and drugs to reduce inflammation (corticosteroids). Blockage of a blood vessel (vascular occlusion) resulting in restricted blood flow and vision disturbances including blindness have been reported following injection of any soft tissue filler in the face especially in the nose, between the eyebrows (glabella), around the eyes (periorbital areas), smile lines (nasolabial folds) and cheek, with a time to onset ranging from immediate to a few weeks following injection. This may appear as whitening of the skin (blanching), discoloration, death of skin (necrosis) or ulceration at the implant site or in the area supplied by the blood vessels affected; or rarely as restriction in blood supply to tissues (ischemic events) in other organs due to blocked blood vessels (embolisation). Isolated rare cases of restriction in blood supply to tissues (ischemic events) affecting the eye leading to visual loss, and the brain resulting in stroke (cerebral infarction), following facial aesthetic treatments have been reported. Reported treatments include medicine to prevent blood clotting (anticoagulant), medicine to treat allergic reactions (epinephrine), aspirin, a medicine to help break down hyaluronic acid in the body (hyaluronidase), drugs to reduce inflammation (corticosteroid treatment), drugs to relieve pain (analgesics), antibiotics, local wound care, drainage, hyperbaric oxygen and surgery. Outcome of the events ranged from resolved to ongoing at the time of last contact. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately. Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own
Post-treatment Checklist
Please observe the following after treatment with Restylane®:
- A cloth dipped in cold water (cold compress), wrung out, and applied to the injected area may be used immediately after treatment to reduce swelling.
- Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- Until there is no redness or swelling, avoid exposure of the treated area to intense heat (sun lamp or sun bathing).
- If you have previously suffered from facial cold sores, there is a risk that the needle punctures could contribute to another occurrence. Speak to your physician about medicine to prevent this from happening again.
- Avoid taking aspirin, non-steroidal anti-inflammatory medications, St. John’s Wort, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site.
User Assistance Information
Your questions about Restylane® can be personally answered by contacting the Galderma Laboratories, L.P. toll-free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday through Friday.
1-855-425-8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised: June 2023
Restylane L
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane-L is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Indication
Restylane-L is indicated for mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. Restylane-L is indicated for submucosal implantation for lip augmentation in patients over the age of 21.
How Supplied
Restylane-L is supplied in a disposable glass syringe with a luer‑lock fitting. Restylane-L is co- packed with sterilized needle(s) as indicated on the carton (29 G x ½").
A patient record label is a part of the syringe label. Remove it by pulling the flap marked with three small arrows. This label is to be attached to patient records to ensure traceability of the product.
The contents of the syringe are sterile.
The volume in each syringe and needle gauge is as stated on the syringe label and on the carton.
Self Life and Storage
Restylane-L must be used prior to the expiration date printed on the package.
Store at a temperature of up to 25° C (77° F). Do not freeze. Protect from sunlight.
Refrigeration is not required.
Do not resterilize Restylane-L as this may damage or alter the product.
Do not use if the package is damaged or if the expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
Contraindications
- Restylane-L is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane-L contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- Restylane-L is contraindicated for patients with bleeding disorders.
- Restylane-L is contraindicated for implantation in anatomical spaces other than the dermis or submucosal implantation for lip augmentation.
- Restylane-L is contraindicated for patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
Warnings
- Defer use of Restylane-L at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
- Injection site reactions (such as swelling, redness, tenderness, pain, bruising or itching) to Restylane® have been observed as consisting mainly of short term minor or moderate inflammatory symptoms starting early after treatment and with less than 7 days duration in the nasolabial folds and less than 14 days duration in the lips. Rare post-market reports of immediate post-injection reactions included extreme swelling of lips, the whole face and symptoms of hypersensitivity such as anaphylactic shock.
- Restylane-L must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar area. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
- Injections of greater than 1.5 mL per lip (upper or lower) per treatment session significantly increases the occurrence of moderate to severe injection site reactions. If a volume of more than 3 mL is needed to achieve optimal correction, a follow-up treatment session isrecommended.
- In a meta-analysis of all Restylane Pre-market Approval Studies (that included 42 patients under the age of 36 and 820 over the age of 35), the incidence of swelling was higher in younger patients (28%) compared to older patients (18%) and incidence of contusion was higher in older patients (28%) compared to younger patients (14%). The majority of these events were mild in severity.
Precautions
- Restylane-L is packaged for single patient use. Do not resterilize. Do not use if package is opened or damaged.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Based on U.S. clinical studies, patients should be limited to 6.0 mL per patient per treatment in wrinkles and folds such as nasolabial folds and to 1.5 mL per lip per treatment. The safety of injecting greater amounts has not been established.
- The safety or effectiveness of Restylane and Restylane-L for the treatment of anatomic regions other than nasolabial folds or lips has not been established in controlled clinical studies. Refer to the clinical studies section for more information on implantation sites that have been studied.
- As with all transcutaneous procedures, Restylane-L implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety of Restylane-L for use during pregnancy, in breastfeeding females or in patients under 18 years has not been established.
- The safety and efficacy of Restylane-L for lip augmentation has not been established in patients under the age of 22 years.
- Formation of keloids may occur after dermal filler injections including Restylane-L. Keloid formation was not observed in studies involving 430 patients (including 151 African-Americans and 37 other patients of Fitzpatrick Skin Types IV, V and VI). For additional information please refer to Studies MA-1400 02, MA‑1400-01, and 31GE0003 in the Clinical Trials Section. In study MA-1100-001 with Restylane and Restylane-L, there were 53.3% (32/60) of patients with Fitzpatrick Skin Types IV, V, and VI and no reports of keloid formation.
- Restylane-L injection may cause hyperpigmentation at the injection site. In a clinical study (MA—1400-01) of 150 patients with pigmented skin (of African American heritage and Fitzpatrick Skin Types IV, V, and VI), the incidence of post-inflammatory hyperpigmentation was 9% (14/150). 50% of these events asted up to six weeks after initial implantation. In study MA-1100-001 with Restylane and Restylane-L there were 53.3% (32/60) of patients with Fitzpatrick Skin Types IV, V, and VI and no reports of hyperpigmentation.
- The safety profile for Restylane lip augmentation in persons of color is based upon information from 38 and 3 subjects with Fitzpatrick Skin Types IV and V, respectively. Within this population, the incidence of adverse events was similar to the overall study population, with the exception that swelling occurred more frequently in persons of color.
- Injection of Restylane-L in patients with pre-existing tendency toward edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up.
- Injection of Restylane-L too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable lumps.
- Restylane-L should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at Restylane-L injection sites. Restylane-L should be used with caution in patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the preceding 3 weeks.
- Avoid injecting Restylane-L into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane-L into an area where an implant other than hyaluronic acid has been placed.
- The safety of Restylane-L with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane-L, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane-L is administered before the skin has healed completely after such a procedure.
- Injection of Restylane-L into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Lidocaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics e.g., certain anti-arrhythmics, since the systemic toxic effects can be additive.
- Lidocaine should be used with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction.
- Individual variation and treatment area may affect the bio-degradation of Restylane-L, in rare cases product remnants has been detected in tissue when the clinical effect has returned to baseline.
- Restylane-L is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Galderma Laboratories, L.P. at 1-855-425-8722.
- Glass is subject to breakage under a variety of unavoidable conditions. Care should be taken with the handling of the glass syringe and with disposing of broken glass to avoid laceration or other injury.
- After use, syringes and needles should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
- Restylane-L should not be mixed with other products before implantation of the device.
Adverse Experiences
There were seven U.S. studies that reported adverse experiences. Five of the seven studies were conducted in support of the indication of mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds, and two of the seven studies were conducted in support of the indication of submucosal implantation for lip augmentation.
Studies conducted in moderate to severe facial wrinkles and folds, such as nasolabial folds.Three U.S. studies (i.e., Study 31GE0003, MA-1400-01, and Study MA-1400-02) involved 430 patients at 33 centers. In study 31GE0003, 138 patients at 6 centers received Restylane injections in 1 side of the face and a bovine collagen dermal filler (Zyplast®) in the other side of the face. In Study MA-1400-01, 150 patients were injected with Restylane on one side of the face and Perlane® on the other side of the face. In study MA-1400-02, 283 patients were randomized to receive either Restylane or Perlane injection on both sides of the face. The adverse outcomes reported in patient diaries during 14 days after treatment in these studies are presented in Tables 1–6. The physician diagnosed adverse events identified in studies MA-1400-01 and MA-1400-02 at 72 hours after injection are presented in Table 9. Table 10 presents all investigator-identified adverse experiences recorded at study visits 2 weeks or more after injection in studies MA-1400-01, MA-1400-02, and 31GE0003.
In the fourth U.S. study (MA-004-03) involving 75 patients at 3 centers, adverse events reported by Restylane patients are presented in Table 11. Patients in the study received Restylane injections in both nasolabial folds at baseline, a second treatment in one nasolabial fold at 4.5 months and in the contralateral nasolabial fold at 9 months.
In a fifth U.S. study (MA-1100-001) 60 patients at three centers randomly received Restylane-L injections on one side of the face and Restylane injections on the other side of the face. The adverse events reported in patient diaries during 14 days after treatment are presented in Tables 7 and 8. The physician recorded adverse events identified in study MA-1100-001 at 14 days after injection are presented in Table 12.
Table 9 shows the number of adverse experiences identified by investigators at 72 hours after injection for Studies MA-1400‑01 and MA-1400-02. Some patients had multiple adverse experiences or had the same adverse experience at multiple injection sites. No adverse experiences were of severe intensity.
Table 10 presents the number of patients and per patient incidence of all adverse experiences identified by investigators at visits occurring two or more weeks after injection.
In a clinical study (31GE0003) in which safety was followed for 12 months with repeat administration of Restylane at six to nine months following the initial correction, the incidence and severity of adverse events were similar in nature and duration to those recorded during the initial treatment sessions.
In all three studies, investigators reported the following local and systemic events that were judged unrelated to treatment and occurred at an overall incidence of less than 2%, i.e., acne; arthralgia; tooth disorders (e.g., pain, infection, abscess, fracture); dermatitis (e.g., rosacea, unspecified, contact, impetigo, herpetic); unrelated injection site reactions (e.g., desquamation, rash, anesthesia); facial palsy with co-administration of botulinum toxin; headache/migraine; nausea (with or without vomiting); syncope; gastroenteritis; upper respiratory or influenza-like illness; bronchitis; sinusitis; pharyngitis; otitis; viral infection; cystitis; diverticulitis; injuries; lacerations; back pain; rheumatoid arthritis; and various medical conditions such as chest pain, depression, pneumonia, renal stones, urinary incontinence, and uterine fibroids.
Table 11 presents the number of patients and per patient incidence and severity of injection site adverse events identified by the investigator. Two subjects had adverse events that were severe, one subject with bilateral facial bruising and one subject with infection at the injection site. These events were considered probably or possibly related and both subjects had their events resolve in approximately 3 weeks.
Table 12 shows the number of adverse events identified by investigators during Day 1 through Day 14 after injection in Study MA-1100-001.
Some patients had multiple adverse events or had the same adverse events at bilateral injection sites. No adverse events were of severe intensity. Patients were queried on adverse events on the day of injection and at the Day 14 visit.
Study MA-1100-001, included 52 subjects who had no prior cosmetic treatment and 8 subjects who had prior dermal filler treatment. There were no statistical differences in the proportion of subjects with adverse events who had prior treatment and those with no prior treatment.
Studies conducted for submucosal implantation for lip augmentation
In the U.S. pivotal study (MA-1300-15) involving 180 subjects at 12 centers, the adverse outcomes reported in subject diaries are presented in Tables 14 and 15. Physician reported treatment emergent adverse events are presented in Table 16. At baseline, subjects were randomized to receive Restylane injections in the lips or no treatment (control group). At 6 months, all subjects were eligible to receive treatment or re-treatment in the lips with Restylane.
Of the 180 subjects enrolled in the study, 172 subjects received their first treatment with Restylane at either baseline/Day 0 or at 6 months, and 93 subjects received a second treatment at 6 months. There were 8 subjects enrolled in the study that were never treated. The number of events and subjects reporting TEAEs decreased between the first and second treatments. 87% of subjects receiving their first treatment reported a total of 795 TEAEs while 65% of subjects that received a second treatment reported a total of 267 TEAEs. Furthermore, an overwhelming majority of these TEAEs were mild in intensity (672/795, 85%; and 264/267, 99%; first and second treatment respectively), and were transient in nature, resolving in approximately 15 days or less.
The study results showed injection of greater than 1.5 mL per lip (upper or lower), per treatment session increased the occurrence of the total of moderate and severe injection site reactions. The incidence was 43% (33/76) for subjects receiving more than 3.0 mL of Restylane and 21% (20/96) for subjects receiving less than 3.0 mL of Restylane in a single treatment session. When optimal correction requires greater than 1.5 mL per upper or lower lip, subsequent treatment using additional product is recommended.
97% of the subjects reported at least one event of swelling, redness, tenderness, or pain in their diaries. These were mainly short-term events, which occurred immediately after treatment and resolved within 14 days. 15% of the subjects reported adverse events (typically swelling and tenderness) that lasted longer than 15 days in their diary. 46% of subjects reported at least one event as “affecting their daily activity” or “disabling.”
Additional safety assessments in the study included lip texture, firmness, symmetry, movement, function, sensation, mass formation, and product palpability, which were evaluated as appropriate at the screening visits and at follow-up visits.
The majority of texture and firmness assessments showed mild abnormalities and lasted for less than 4 weeks. Sixteen subjects reported severe asymmetry (difference > 2 mm) post-treatment, which all resolved within 4 weeks. GAIS assessments by these 16 subjects were rated as at leas improved during those visits.
Assessments made by the trained health care provider showed 92% of subjects had product palpability at week 8, and 61% at week 24. The majority of palpations were rated as “expected feel.” 3% of the subjects reported “unexpected feel” during the study, all of which were resolved with massaging.
One subject reported one mass formation (mucocele) during the study. The mucocele was drained and resolved by the next visit.
All other lip safety assessments showed no remarkable findings.
In the pilot study MA-1300-13K, 20 subjects were enrolled at 1 center and received Restylane for lip augmentation. Subjects were followed up through 24 weeks. Seven adverse events were reported. Two of the seven events, which were mild bruising, were related to injection procedure. The adverse outcomes reported in subject diaries are presented in Table 17.
Table 16 presents commonly reported (≥ 5%) treatment emergent adverse events (TEAEs) by reatment group.
For study MA-1300-13K, seven treatment emergent adverse events were experienced by four subjects. Two of these events, mild bruising, were considered related to treatment.
Directions For Assembly
Syringe with white cap:
Use your thumb and forefinger to hold firmly around both the syringe barrel and the luer-lock adapter part (C) of the closure system. With your other hand, take hold of the white cap (A) at the end of the closure system and gently tilt back and forth carefully until cap disconnects and can be pulled off (seal will be broken).
Do not rotate.
Do not touch the syringe tip (B) to keep it sterile.
Syringe with transparent cap:
Unscrew the tip cap of the syringe carefully.
Assembly Of Needle To Syringe
Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the luerlock adapter (C). Grasp the needle shield with the other hand. To facilitate proper assembly, both push and rotate firmly clockwise. Make sure the needle is screwed on all the way so that the needle shield touches the luer lock adapter (C). To remove the needle shield, hold the syringe and the luer- lock adapter. With your other hand hold the needle shield and pull straight out. Do not rotate.
Pre-Treatment Guidlines
Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John’s Wort, or high doses of Vitamin E supplements. These agents may increase bruising and bleeding at the injection site.
Treatment Procedures
1. It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the Restylane-L treatment. Advise the patient of the necessary precautions before commencing the procedure.
2. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block.
3. The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
4. Sterile gloves are recommended while injecting Restylane-L.
5. Before injecting, press rod carefully until a small droplet is visible at the tip of the needle.
6. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify that the needle is not intravascular.
7. Restylane-L is administered using a thin gauge needle (29 G x ½"). The needle is inserted at an approximate angle of 30° parallel to the length of the wrinkle, fold, or lip. For nasolabial folds, Restylane-L should be injected into the mid-to-deep dermis. For lip augmentation, Restylane-L should be injected into the submucosal layer, care should be taken to avoid intramuscular injection. If Restylane-L is injected too superficially this may result in visible lumps and/or bluish discoloration.
8. Inject Restylane-L applying even pressure on the plunger rod. Do not apply excessive pressure to the syringe at any time. If resistance is encountered, the needle should be partially withdrawn and repositioned, or fully withdrawn, checked for function and replaced if needed. It is important that the injection is stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
9. Only correct to 100% of the desired volume effect. Do not overcorrect. With cutaneous deformities the best results are obtained if the defect can be manually stretched to the point where it is eliminated. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue and the injection technique.
10. Typical usage for each treatment session is specific to the site as well as wrinkle severity. In a prospective study of midface wrinkle correction, the median total dose was 3.0 mL. Based on U.S. clinical studies, the maximum recommended dose per treatment is 6.0 mL for the nasolabial folds and 1.5 mL per lip per treatment.
Injection Technique
1. Restylane-L can be injected by a number of different techniques that depend on the treating physician’s experience and preference, and patient characteristics.
2. Serial puncture (A) involves multiple, closely spaced injections along wrinkles or folds. Although serial puncture allows precise placement of the filler, it produces multiple puncture wounds that may be undesirable to some patients.
3. Linear threading (includes retrograde and antegrade) (B) is accomplished by fully inserting the needle into the middle of the wrinkle or fold and injecting the filler along the track as a “thread.” Although threading is most commonly practiced after the needle has been fully inserted and is being withdrawn, it can also be performed while advancing the needle (“push- ahead” technique). To enhance the vermillion of the lip, the retrograde linear threading technique is the most advisable
4. Serial threading is a technique that utilizes elements of both approaches.
5. Cross-hatching (C) consists of a series of parallel linear threads injected at intervals of five to ten mm followed by a new series of threads injected at right angles to the first set to form a grid. This technique is particularly useful in facial contouring when coverage of the treatment region needs to be maximized.
Note! The correct injection technique is crucial for the final result of the treatment
A. Serial Puncture
B. Linear Threading (includes retrograde and antegrade)
C. Cross-hatching
6. Dissection of the sub-epidermal plane with lateral movement of the needle, rapid flows (>0.3 mL/min), rapid injection or high volumes may result in an increase in short-term episodes of bruising, swelling, redness, pain, or tenderness at the injection site.
7. It is recommended to change needle for each new treatment site.
8. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area firmly between your fingers or against an underlying area to obtain optimal results.
9. If so called “blanching” is observed, i.e., the overlying skin turns a whitish color, the injection should be stopped immediately and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with the American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection1
10. If the wrinkles or lips need further treatment, the same procedure should be repeated until a satisfactory result is obtained. Additional treatment with Restylane-L may be necessary to achieve the desired correction.
11. If the treated area is swollen directly after the injection, an ice pack can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
12. Patients may have mild to moderate injection site reactions, which typically resolve in less than 7 days in the nasolabial folds and less than 14 days in the lip.
Sterile Needles
- Follow national, local or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided.
- Discard unshielded needles in approved sharps collectors.
- Restylane-L is provided with a needle that does not contain engineered injury protection.
- Administration of Restylane-L requires direct visualization and complete and gradual insertion of the needle making engineered protections infeasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
Q: What is Restylane-L?
A: Restylane-L® is a crystal clear injectable gel composed of hyaluronic acid, a natural substance that already exists in the body. Restylane-L is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. Restylane-L is nonanimal based and free from animal protein. Allergy pretesting is not necessary. Restylane-L contains 0.3% lidocaine. The lidocaine in Restylane-L has been added to reduce the discomfort associated with the treatment.
Q: How does Restylane-L work?
A: Restylane-L is injected into the skin with an ultrafine needle to plump the skin to smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth (nasolabial folds) or into your lips for patients over the age of 21 for lip enhancement.
Q: Why add lidocaine to Restylane?
A: Lidocaine was added to Restylane-L to reduce the pain and discomfort during and after injection. In a clinical study, 60 patients received Restylane® on one side of the face and Restylane-L® on the other side of the face. Restylane-L had an effect on reducing pain. At the time of injection, patients rated their pain about 45 on a scale of 0 to 100 for the side of the face treated with Restylane. In comparison, patients rated their pain about 15 on the same scale for the side of the face treated with Restylane-L. Patients reported less pain on the side of the face treated with Restylane-L up to 60 minutes after treatment.
Q: How long does Restylane-L last?
A: Restylane-L effects generally last about six months and gradually disappear from the body.
Q: Has Restylane-L been studied?
A: A clinical study was conducted with Restylane-L to evaluate the pain reducing effect up to 60 minutes after injection. This study enrolled 60 patients with moderate to severe nasolabial fold wrinkles. The study included 58 female patients and 2 male; 34 were White, 21 were Hispanic or Latino, 3 were African American, 1 was Asian, and 1 was “Other.” In this study, 71.7% of patients experienced less pain after injection of Restylane-L than with Restylane alone. Please see the below table for additional information.
In addition to evaluating the pain reducing effects, the study assessed patient satisfaction with Restylane-L treatment. All 60 subjects were asked to rate the level of improvement seen in their nasolabial folds after injection with Restylane-L. At day fourteen after injection, 100% saw some improvement (Improved, Much Improved, and Very Much Improved). See below table for additional details.
Safety
Q: Who should not use Restylane-L (Contraindications)?
A: Safety has not been established and should not be used in people who are:
- Pregnant
- Breastfeeding
- Trying to become pregnant
- Under the age of 22 for lip enhancement
- Under the age of 18 or over the age of 65
- Highly allergic (for example: gram-positive bacteria)
- Prone to bleeding disorders
Q: What are some warnings to consider?
A: The use of Restylane-L at sites with skin sores, pimples, rashes, hives, cysts, or infections should be postponed until healing is complete. Use of Restylane-L in these instances could delay healing or make your skin problems worse. You may experience skin discoloration (bruising), swelling, redness, tenderness, pain, itching, or small lumps in the area where you are injected. If any of these events occur, the majority usually last one to two weeks. If any symptom lasts longer than two weeks, call the doctor who administered the Restylane-L injection.
Red or swollen small bumps (inflammatory papules) may rarely occur. You may need antibiotics to treat them. In clinical studies, swelling was higher in younger patients (28%) compared to older patients (18%), and bruising was higher in older patients (28%) compared to younger patients (14%). The majority of these events were mild.
If you are injected with Restylane-L into your lips, your physician should be able to feel the product when touching your lips.
Q: What are some potential risks you may encounter?
A: As with all procedures like this, the injection of Restylane-L carries a risk of infection and formation of scar tissue.
The safety and effectiveness of Restylane-L have not been established in pregnant or nursing mothers, and in patients under 18 or over 65 years of age. Restylane-L use while nursing could harm you or the nursing child. Restylane-L should not be used for lip enhancement in patients under the age of 22.
The use of Restylane-L in African-American patients can result in darkening of skin color (hyperpigmentation), which may take several weeks to correct. If you have previously had facial cold sores, an injection can cause them to come back. The safety of Restylane-L used with other skin therapies such as laser, mechanical or chemical peeling, and hair removal has not been established. The use of Restylane-L with these skin therapies may lead to other side effects such as inflammation.
You should avoid exposing the area(s) treated with Restylane-L to excessive sun or UV lamps, and extreme heat and cold until any redness or swelling has disappeared.
Troubleshooting
Q: When should I call my doctor?
A: Most side effects like bruising, swelling, pain, tenderness, redness, and itching will usually go away within one to two weeks. Call your doctor if you have persistent problems beyond 14 days.
Blisters or skin sores that recur may signal the presence of a herpes infection that must be treated.
You can develop an infection that should be treated with antibiotics. If you experience any signs of infection such as fever, redness that spreads to surrounding areas, drainage, increasing tenderness, or increasing pain that does not go away, you should call your doctor.
Seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure (http://www.nlm.nih.gov/medlineplus/stroke.html).
Restylane-L®
Administration
Q: What is Restylane-L?
A: Restylane-L® is a crystal clear injectable gel composed of hyaluronic acid, a natural substance that already exists in the body. Restylane-L is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. Restylane-L is nonanimal based and free from animal protein. Allergy pretesting is not necessary. Restylane-L contains 0.3% lidocaine, which has been added to reduce the discomfort associated with the treatment.
Q: How does Restylane-L work?
A: Restylane-L is injected into the skin with an ultrafine needle to plump the skin and smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth (nasolabial folds) or into your lips for patients over the age of 21 for lip enhancement.
Q: Why add lidocaine to Restylane?
A: Lidocaine was added to Restylane-L to reduce the pain and discomfort during and after injection. In a clinical study, 60 patients received Restylane® on one side of the face and Restylane-L® on the other side of the face. Restylane-L had an effect on reducing pain. At the time of injection, patients rated their pain about 45 on a scale of 0 to 100 for the side of the face treated with Restylane. In comparison, patients rated their pain about 15 on the same scale for the side of the face treated with Restylane-L. Patients reported less pain on the side of the face treated with Restylane-L up to 60 minutes after treatment.
Q: How long does Restylane-L last?
A: Restylane-L effects generally last about six months and gradually disappear from the body.
Q: Has Restylane-L been studied?
A: A clinical study was conducted with Restylane-L to evaluate the pain reducing effect up to 60 minutes after injection. This study enrolled 60 patients with moderate to severe nasolabial fold wrinkles. The study included 58 female patients and 2 male; 34 were White, 21 were Hispanic or Latino, 3 were African American, 1 was Asian, and 1 was “Other.” In this study, 71.7% of patients experienced less pain after injection of Restylane-L than with Restylane alone.
In addition to evaluating the pain reducing effects, the study assessed patient satisfaction with Restylane-L treatment. All 60 subjects were asked to rate the level of improvement seen in their nasolabial folds after injection with Restylane-L. At day fourteen after injection, 100% saw some improvement (Improved, Much Improved, and Very Much Improved).
Post Marketing Surveillance
Q: Have there been adverse events reported through post-market surveillance?
A: The adverse events received from post-marketing surveillance (voluntary reporting and published literature) for Restylane with and without lidocaine in the U.S. and other countries most commonly included reports of transient swelling (edema) and inflammatory reactions with immediate or delayed onset, up to several weeks after treatment.
The following events were also reported in decreasing order of frequency:
- Lumps or bumps (mass formation), hardening (induration)
- Short duration of effect
- Skin redness (erythema)
- Pain or tenderness
- Bruising (hematoma)
- Small bumps (papules or nodules)
- Presumptive bacterial infections and pus (abscess formation)
- Skin discoloration (hyperpigmentation)
- Injection site reactions including burning sensation, warmth, irritation
- Restricted blood flow leading to the death of skin (ischemia and necrosis)
- Allergic reaction (hypersensitivity), rapid swelling (angioedema)
- Eye disorders such as dry eye, eye irritation, eye pain, eye swelling, increased flow of tears (increased lacrimation), eyelid drooping (eyelid ptosis) and visual disturbance including blurred vision, reduced vision, and blindness
- Reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia), tremor, and facial nerve paralysis
- Itching (pruritus)
- Leakage of product from implant site (extrusion of device)
- Scarring
- Small area of inflammation in tissue (granuloma)
- Device dislocation
- Symptoms of reactivation of herpes infection
- Rash
- Blisters/vesicles
- Spider veins/broken capillaries (telangiectasia)
- Abnormal connection between two body parts (fistula)
- Leakage from implant site (effusion/discharge)
- Acne
- Skin inflammation (dermatitis)
- Hives (urticaria)
- Muscle disorders such as muscle twitching and muscle weakness
- Encapsulation of gel in the tissue
- Fungal infection of the skin (dermatophytosis)
- Other dermatological events including dry skin, skin wrinkling, peeling of skin, and localized hair loss (alopecia)
- Non-dermatological events including headache, discomfort (malaise), fever, dizziness, sinus infection, shortness of breath (dyspnea), feeling tired (fatigue), influenza-like illness, insomnia, nausea, and anxiety
The treatments of these events included ice, massage, warm compress, nitroglycerine paste, drugs to reduce inflammation (corticosteroids), antibiotics, medicine that prevents the clotting of blood (anticoagulants), drugs to relieve allergy symptoms (antihistamines), drugs to relieve pain (analgesics), antiviral agents, medicine to relieve the body of excess fluid (diuretic agents), surgical procedure (incision and drainage), or a medicine used to help breakdown hyaluronic acid in the body (hyaluronidase).
The most commonly reported serious adverse events were infection/pocket of pus (abscess), restricted blood flow leading to the death of skin (ischemia/necrosis), scarring, vision loss, allergic reactions (hypersensitivity), scarring, and areas of inflammation in tissue (granuloma) including cases of hardening (mass/induration). Other serious events included common related symptoms such as swelling, pain/tenderness, skin redness (erythema), reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia), inflammation, bruising, and skin discoloration. Serious infections/pocket of pus (abscess) were reported with a time to onset ranging from one day to six months following the injection.
The infections usually resolved after two days up to a few months, and most of the patients had recovered or were recovering at the time of last contact.
The treatments included antibiotics, drugs to relieve pain (analgesics), drugs to reduce inflammation (corticosteroids), and hyaluronidase (a medicine to help break down the Restylane-L so that it is more easily absorbed).
Serious small areas of inflammation in tissue (granuloma), including hardening, were reported with a time to onset ranging from a month up to a year or longer. The outcomes were mostly recovered or recovering at the time of last contact. Treatment included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines), antibiotics, drugs to reduce inflammation (corticosteroids), and surgical removal (excisions). Incisions to examine tissue (biopsies) have been taken in some cases, but the majority of cases are non-biopsy confirmed.
Serious allergic reactions (hypersensitivity) were reported in most cases with a time to onset ranging from immediately to a few weeks post-injection. Most of the events were recovered or recovering at the time of last contact. The treatments included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines), antibiotics, and drugs to reduce inflammation (corticosteroids).
Blockage of a blood vessel (vascular occlusion) resulting in restricted blood flow and vision disturbances, including blindness, have been reported following injection of any soft tissue filler in the face, especially in the nose, between the eyebrows (glabella), around the eyes (periorbital areas), smile lines (nasolabial folds), and cheek, with a time to onset ranging from immediate to a few weeks following injection. This may appear as whitening of the skin (blanching), discoloration, death of skin (necrosis), or ulceration at the implant site or in the area supplied by the blood vessels affected; or rarely as restriction in blood supply to tissues (ischemic events) in other organs due to blocked blood vessels (embolisation).
Isolated rare cases of restriction in blood supply to tissues (ischemic events) affecting the eye leading to visual loss, and the brain resulting in stroke (cerebral infarction), following facial aesthetic treatments have been reported. Reported treatments include medicine to prevent blood clotting (anticoagulant), medicine to treat allergic reactions (epinephrine), aspirin, a medicine to help break down hyaluronic acid in the body (hyaluronidase), drugs to reduce inflammation (corticosteroid treatment), drugs to relieve pain (analgesics), antibiotics, local wound care, drainage, hyperbaric oxygen, and surgery.
Outcome of the events ranged from resolved to ongoing at the time of last contact. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
User Assistance Information
User Assistance Information
Your questions about Restylane-L can be personally answered by contacting the Galderma Laboratories, L.P.
toll-free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday through Friday.
1-855-425-8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised: June 2023
Restylane Slik
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane Silk is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Indication
Restylane Silk is indicated for submucosal implantation for lip augmentation and derma implantation for correction of perioral rhytids in patients over the age of 21.
How Supplied
Restylane Silk is supplied in a disposable glass syringe with a luer-lock fitting. Restylane Silk is co-packed with sterilized needle(s) 30 G x ½” as indicated on the carton. A patient record label is a part of the syringe label. Remove it by pulling the flap marked with three small arrows. This label is to be attached to patient records to ensure traceability of the product.
The contents of the syringe are sterile. The volume in each syringe and needle gauge is as stated on the syringe label and on the carton.
Self Life and Storage
Restylane Silk must be used prior to the expiration date printed on the package. Store at a temperature of up to 25° C (77° F). Do not freeze. Protect from sunlight. Refrigeration is not required.
Do not resterilize Restylane Silk as this may damage or alter the product.
Do not use if the package is damaged or if expiry date or lot number is missing or illegible.
Immediately return the damaged product to Galderma Laboratories, L.P.
Contraindications
- Restylane Silk is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane Silk contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- Restylane Silk is contraindicated for patients with bleeding disorders.
- Restylane Silk is contraindicated for implantation in anatomical spaces other than the dermis or submucosal implantation for lip augmentation.
- Restylane Silk should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
Warnings
- Defer use of Restylane Silk at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection or tumors, in or near the intended treatment site is present until the process has been controlled.
- Injection site reactions (e.g., lip swelling, lip pain, and contusion) to Restylane Silk have been observed as consisting mainly of short-term minor or moderate inflammatory symptoms starting shortly after treatment, with an average of less than 18 days duration in the lips. In some cases delayed onset of these events has been observed with a range of 21 to 142 days after treatment. Most events with delayed onset resolved within 18 days. Injection site swelling appears to occur more frequently with the linear antegrade method of injection. Rare post-market Restylane reports of immediate post injection reactions included extreme swelling of lips, the whole face and symptoms of hypersensitivity such as anaphylactic shock.
- Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Restylane Silk must not be implanted into blood vessels. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar area. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
- Injections of 3.0 mL or greater (upper and lower lip combined) per treatment session increases the occurrence of injection site reactions. If a volume of more than 3 mL is needed to achieve optimal correction, a follow-up treatment session is recommended.
- As with all dermal filler procedures, Restylane Silk should not be used in vascular rich areas. Use of similar products in these areas, such as glabella and nose, has resulted in cases of vascular embolization and symptoms consistent with ocular vessel occlusion, such as blindness. For additional information please see the Post-Marketing Surveillance in Adverse Events.
Precautions
- Restylane Silk is packaged for single patient, single session use. Do not resterilize. Do not use if package is opened or damaged.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- The safety or effectiveness of Restylane Silk for the treatment of anatomic regions other than lips or perioral rhytids has not been established in controlled clinical studies. Refer to the clinical studies section for more information on implantation sites that have been studied.
- The safety and effectiveness of cannula injection of Restylane Silk have only been clinically evaluated in two brands of blunt-tip cannulas (DermaSculpt and Softfil) that are 25G-27G and 11/2 inches in length.
- The safety or effectiveness of Restylane Silk for the treatment of perioral rhytids with a small bore, blunt tip cannula has not been established in controlled clinical studies.
- The safety and effectiveness of Restylane Silk for lip augmentation has not been established in patients under the age of 22 years. There is limited information on the safety of Restylane Silk in patients less than 36 years of age. In a premarket study of Restylane Silk with needle injection (MA-170004), the incidence of injection site reactions in 60 patients less than 36 years was similar to the 157 patients between the ages of 36 and 65 years. The majority of these injection site reactions were mild in severity. In the premarket study of Restylane Silk with cannula injection (43USC1505), 17 subjects less than 36 years of age were studied, and the incidence of injection site reactions were similar to the 43 subjects between the ages of 36 and 72 years.
- As with all transcutaneous procedures, Restylane Silk implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety of Restylane Silk for use during pregnancy, in breastfeeding females or in patients under 18 years has not been established
- The safety in patients with known susceptibility to keloid formation has not been studied. Formation of keloids may occur after dermal filler injections including Restylane Silk. In a premarket study of Restylane Silk with needle injection (MA1700-04), the incidence and severity of adverse events in 51 subjects with Fitzpatrick Skin Types IV (n=48) and V (n=3) was similar to that reported in the general population and no unique adverse events associated with these patient subgroups was observed. In the premarket study of Restylane Silk with cannula injection (43USC1505), the incidence and severity of adverse events in 13 subjects with Fitzpatrick Skin Types IV (n=8), V (n=3), and VI (n=2) were similar to those reported in the general population and no unique adverse events associated with these patient subgroups was observed.
- Hyperpigmentation may occur after dermal filler injections including Restylane Silk. Hyperpigmentation was not observed in the two Restylane Silk studies of 281 total subjects including subjects with Fitzpatrick Skin Types IV (n=56), V (n=6), and VI (n=2).
- The safety profile for Restylane Silk lip augmentation in persons of color is based upon information from 64 total subjects with Fitzpatrick Skin Types IV, V and VI from two clinical studies (MA-1700-04 and 43USC1505). Within this population, the incidence of adverse events was similar to the overall study population.
- Restylane Silk should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at Restylane Silk injection sites. Patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the 3 weeks preceding treatment with Restylane Silk have not been studied.
- Avoid injecting Restylane Silk into areas in close proximity to implants other than hyaluronic acid, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment.
- After use, syringes and needles/blunt cannula should be handled as potential biohazards.
- Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
- The safety of Restylane Silk with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane Silk, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane Silk is administered before the skin has healed completely after such a procedure.
- Injection of Restylane Silk into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Individual variation and treatment area may affect the bio-degradation of Restylane Silk and product might be detected in the tissue even after the clinical effect has disappeared.
- Restylane Silk is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Galderma Laboratories, L.P. at 1-855-425-8722. Glass is subject to breakage under a variety of unavoidable conditions. Care should be taken with the handling of the glass syringe and with disposing of broken glass to avoid laceration or other injury.
- Restylane Silk should not be mixed with other products before implantation of the device.
- Restylane Silk contains lidocaine. If additional dental block or topical lidocaine or other local anesthetics or agents structurally related to amide type local anesthetics are used concurrently with the product the following considerations should be observed: − Use with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction − High doses of lidocaine (more than 4.5 mg/kg of bodyweight) can cause acute toxic reactions manifesting as symptoms affecting the central nervous system and cardiac conduction − Systemic toxic effects could be additive.
Adverse Experiences
There were two U.S. studies that reported adverse experiences. One study was conducted in support of the indication for submucosal implantation for lip augmentation and dermal implantation for correction of perioral rhytids, and one study was conducted in support of using a small bore, blunt-tip cannula for submucosal implantation for lip augmentation.
Study conducted for submucosal implantation for lip augmentation and dermal implantation for correction of perioral rhytids The U.S. pivotal study (MA-1700-04) involved 221 subjects at 14 centers. At baseline, subjects were randomized to receive Restylane Silk injections in the lips and perioral rhytids (as needed) or no treatment (control group). At 6 months, all subjects were eligible to receive treatment or re-treatment in the lips and perioral rhytids with Restylane Silk.
Of the 221 subjects enrolled in the study, 218 subjects received their first treatment with Restylane Silk at either baseline/Day 0 or at 6 months, and 33 subjects received a second treatment at 6 months. Safety was also evaluated for subjects with Fitzpatrick skin types IV and V (n=52) and for the subgroup of subjects ≤ 35 years of age (n=60).
An adverse event (AE) was defined as any untoward medical occurrence or an unintended sign, symptom, or disease temporally associated with the use of the device, whether or not considered related to the device. An AE was further defined as:
- any diagnosis, sign, symptom, or abnormal laboratory value not present, detected or complained of at the baseline assessment. An AE that occurred during the study was considered a treatment emergent adverse event
(TEAE) if:
- it was not present prior to receiving treatment (as determined by onset date of event and date treatment was received), or
- it was present prior to receiving treatment but the severity increased after treatment (as determined by onset date of the severity increase of the event and date treatment was received).
The investigator was to classify the severity of an adverse event according to the following
definitions:
- Mild: did not interfere with routine activities, could perform daily functions
- Moderate: interfered with routine activities, could perform daily functions, but with concerted effort
- Severe: unable to perform routine activities A Serious Adverse Device Event (SADE) was defined as an AE that:
- results in death;
- is life-threatening;
- results in permanent impairment of a body function;
- results in permanent damage to a body structure; or,
- necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
Subjects were asked to grade symptoms of bruising, redness, swelling, pain, tenderness and itching. Subject’s scores for the severity of these events are presented in Table 2 and durations are provided in Table 3. The majority of events (>85%) were mild in intensity and resolved in 2 – 7 days. Eight patients reported diary symptoms of “Affects Daily Activities” and “Disabling” that lasted longer than 7 days. These events were: Swelling (n=6), pain (n=2), tenderness (n=3), bruising (n=3), itching (n=2), and redness (n=1).
- any diagnosis, sign, symptom, or abnormal laboratory value noted at baseline that worsened in severity or intensity or increased in frequency during the study.
The treatment-emergent adverse events (TEAEs) reported during the study are presented in
Clinical Trials
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Directions For Assembly
For safe use of Restylane Silk, it is important that the needle/blunt cannula is properly assembled.
Syringe with white cap:
Hold the syringe on the ribbed part (C) of the white closure system (luer-lock adapter).
With your other hand, take hold of the white cap (A) at the end of the closure system and gently tilt back and forth carefully until cap disconnects and can be pulled off (seal will be broken).
Do not rotate.
Do not touch the syringe tip (B) to keep it sterile.
Syringe with transparent cap:
Unscrew the tip cap of the syringe carefully.
Assembly Of Needle To Syringe
Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the luerlock adapter. Grasp the needle shield (or hub if using a cannula) with the other hand. To facilitate proper assembly, both push and rotate firmly.
Pre-Treatment Guidlines
Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti inflammatory medications, St. John’s Wort, or high doses of Vitamin E supplements. These agents may increase bruising and bleeding at the injection site.
Treatment Procedures
1. It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the Restylane Silk treatment. Advise the patient of the necessary precautions before commencing the procedure.
2. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block.
3. The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
4. Sterile gloves are recommended while injecting Restylane Silk.
5. Before injecting, press rod carefully until a small droplet is visible at the tip of the needle.
6. When using needle, after insertion, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify that the needle is not intravascular.
7. Restylane Silk is administered using a thin gauge needle (30 G x ½”) or as an alternative a blunt tip cannula (recommended gauge sizes 25-27G) can be used. Please note use of a cannula is intended for lip augmentation only whereas needles may be used to treat both lips and perioral rhytids.
8. When using a needle, the needle is inserted at an approximate angle of 30° parallel to the length of the wrinkle, fold, or lip. For rhytids, Restylane Silk should be injected into the mid-to-deep dermis. Restylane Silk should be injected into the submucosal layer for lip augmentation, care should be taken to avoid intramuscular injection. If Restylane Silk is injected too superficially this may result in visible lumps and/or bluish discoloration. When using a cannula for lip augmentation, an entry point is made in the skin, e.g. with a sharp needle of appropriate size. Inject slowly. It is recommended to change needle/cannula for each new treatment site.
9. Inject Restylane Silk applying even pressure on the plunger rod. Do not apply excessive pressure to the syringe at any time. Presence of scar tissue may impede advancement of the needle/cannula. If resistance is encountered the needle/cannula should be partially withdrawn and repositioned or fully withdrawn and checked for function and replaced if needed.
10. It is important that the injection is stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
11. Only correct to 100% of the desired volume effect. Do not overcorrect. With cutaneous deformities the best results are obtained if the defect can be manually stretched to the point where it is eliminated. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue and the injection technique.
12. Typical usage for each treatment session is specific to the site as well amount of augmentation or rhytids correction desired. Based on U.S. clinical studies, the maximum recommended dose per treatment is 1.5 mL per lip per treatment or 1.0 mL for perioral rhytid correction.
Injection Technique
1. Restylane Silk can be injected by a number of different techniques that depend on the treating physician’s experience and preference, and patient characteristics.
2. Serial puncture (only recommended for needle) (A) involves multiple, closely spaced injections along wrinkles or folds. Although serial puncture allows precise placement of the filler, it produces multiple puncture wounds that may be undesirable to some patients.
3. Linear threading (includes retrograde and antegrade) (B) is accomplished by fully inserting the needle/cannula into the middle of the wrinkle or fold and injecting the filler along the track as a “thread.” Although threading is most commonly practiced after the needle/cannula has been fully inserted and is being withdrawn, it can also be performed while advancing the needle/cannula (“push-ahead” technique). To enhance the vermillion of the lip, the retrograde linear threading technique is the most advisable.
4. Serial threading is a technique that utilizes elements of both approaches
Note! The correct injection technique is crucial for the final result of the
treatment.
A. Serial Puncture (only recommended for needle)
B. Linear Threading (includes retrograde and antegrade)
5. Dissection of the sub-epidermal plane with lateral movement of the needle, rapid flows (>0.3 mL/min), rapid injection or high volumes may result in an increase in short-term episodes of bruising, swelling, redness, pain, or tenderness at the injection site.
6. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area firmly between your fingers or against an underlying area to obtain optimal results.
7. If so called “blanching” is observed, i.e., the overlying skin turns a whitish color, the injection should be stopped immediately and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with the American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection1.
8. If the wrinkles or lips need further treatment, the same procedure should be repeated until a satisfactory result is obtained. Additional treatment with Restylane Silk may be necessary to achieve the desired correction.
9. If the treated area is swollen directly after the injection, an ice pack can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
10. Patients may have mild to moderate injection site reactions, which typically resolve in less than 18 days in the lip.
Sterile Needles
Follow national, local or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided. • Discard unshielded needles in approved sharps collectors.
Restylane Silk is provided with a needle that does not contain engineered injury protection. Administration of Restylane Silk requires direct visualization and complete and gradual insertion of the needle making engineered protections infeasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane Silk?
Restylane Silk is a smooth, clear injectable gel composed of hyaluronic acid (HA). HA is a naturally occurring sugar found in the human body. HA fillers, including Restylane Silk, contains HA that has been modified to last longer in the body than the naturally occurring HA. Restylane Silk contains 0.3 % lidocaine to reduce pain during injection.
What is it used for?
Restylane Silk is injected into the lips and the lines around the mouth to temporarily add fullness to the lips and help smooth the lines around the mouth in patients over the age of 21.
How does it work?
Restylane Silk is injected with an ultrafine needle or a small, blunt‐tipped cannula into your lips to add fullness. It can also be injected with an ultrafine needle into the skin to help smooth the wrinkles around your mouth (perioral lines). The picture below shows the treatment areas for Restylane Silk.
Safety
What precautions should my doctor discuss with me?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications:
- The use of Restylane Silk where skin sores, pimples, rashes, hives, cysts, or infections are present should be postponed until healing is complete. Use of Restylane Silk where these are present could delay healing or make your skin problems worse.
- Tell your doctor if you are using St. John’s Wort, blood thinners, high doses of Vitamin E supplements, aspirin, and other NSAIDs, such as ibuprofen, because these may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning other skin therapies such as laser, mechanical or chemical peeling, and hair removal after treatment. The use of Restylane Silk with these skin therapies may lead to other side effects such as inflammation.
- After treatment with Restylane Silk, you should minimize exposure to the sun or UV lamps, and avoid being in the heat and cold until any redness or swelling has disappeared. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are pregnant, thinking about becoming pregnant, or breastfeeding. The safety and effectiveness of Restylane Silk has not been established in pregnant women or nursing mothers.
- Tell your doctor if you are on a therapy to decrease the body’s immune response. Treatment may result in an increased risk of infection.
- Tell your doctor if you have a history of thick, hard scars (excessive scarring). The safety and effectiveness of Restylane Silk in patients with a history of thick, hard scars has not been studied and may result in additional scarring.
- Tell your doctor if you have a dental block or use topical lidocaine at the same time as the filler treatment. High doses of lidocaine could cause a toxic reaction.
- The safety of Restylane Silk has not been established in people who are under the age of 22 years or over 65 years.
- Restylane Silk should only be used to be injected into the lips and wrinkles around the lips (perioral lines). It should not be used in other parts of the face and body.
Troubleshooting
When should I call my doctor?
You should call your doctor immediately if you have:
- Changes in your vision
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
- White appearance of the skin
- Unusual pain during or shortly after treatment
Be sure to call your doctor if you have:
- Persistent injection site reactions beyond 14 days, as most side effects such as bruising, swelling, pain, tenderness, redness, and itching will usually go away within one to two weeks.
- Blisters or skin sores that recur, which may signal the presence of a herpes infection
- Any signs of infection such as fever, redness that spreads to surrounding areas, drainage, increasing tenderness or increasing pain that does not go away
- Significant pain away from the injection site
- Any side effect that occurs weeks or months after treatment
- Any other symptoms that cause you concern.
Administration
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Post Marketing Surveillance
What side effects have been reported voluntary of Restylane Silk use in and outside of
the United States?
The most commonly reported serious adverse events were restricted blood flow leading to the death of skin (ischemia/necrosis), infection and abscess formation and allergic reactions (hypersensitivity reactions). Other serious events included common related symptoms such as swelling, pain/tenderness, skin redness (erythema) and bruising.
- Restricted blood flow occurred within immediately or up to 3 days after injection. Treatment included hyaluronidase, aspirin, nitroglycerin, corticosteroids, and antibiotics. In addition, warm compresses, massage and arnica were used.
- Infection and abscess formation occurred 2 to 52 days after injection. Treatment included hyaluronidase, corticosteroids and antibiotics. In addition, warm compresses, drainage, aspiration and ice were used.
- Allergic reactions occurred immediately or up to 10 days after injection. Treatment included hyaluronidase, antihistamine, antibiotics and corticosteroids.
- Swelling and edema occurred immediately or up to 80 days after injection. Treatment included hyaluronidase, antibiotics, NSAID, corticosteroids. In addition, aspiration and ice were used.
- Pain/tenderness occurred immediately to 14 days after injection. Treatment included corticosteroids and NSAID.
- Skin redness occurred immediately or up to 21 days after injection. Treatment included NSAID. In addition, ice was used.
- Bruising occurred one day after treatment. Treatment included NSAID. In addition, ice was used and the area was massaged.
Additionally, there have been reports of:
- hardening (mass/induration)
- lack of effect,
- small bumps (papules/nodules)
- skin discoloration/darkening skin tone (hyperpigmentation)
- rapid swelling (angioedema)
- injection site reactions such as burning sensation, discomfort, dryness, exfoliation, irritation, and warmth
- injury or compression to blood vessels (vascular events)
- inflammation
- tingling sensation (paresthesia) and reduced sense of touch (hypoesthesia)
- itching (pruritus)
- vision abnormalities
- symptoms of reactivation of herpes infection
- rash (dermatitis)
- implanted gel moving from site of injection (device displacement)
- blisters
- uneven appearance of the skin (asymmetry/deformity)
- scarring
- hives (urticaria)
- leakage from implant site
- small area of inflammation in tissue (granuloma/foreign body reaction)
- dilated small blood vessels (telangiectasia)
- acne
- muscular weakness
- dry lips, dry skin, skin wrinkling, and peeling of skin
- fever (pyrexia), anxiety, feeling tired (fatigue), headache and insomnia. Delayed‐onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed‐onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
What should patients do after receiving treatment?
- A clean cloth dipped in cold water (cold compresses) wrung out, and applied to the injected area may be used immediately after treatment to reduce swelling.
- Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- Avoid taking aspirin, NSAID, St. John’s Wort, blood thinners, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site.
- Minimize strenuous exercise and exposure to excessive heat, sun, or UV lamps for the first 24 hours after treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site. Until there is no redness or swelling, avoid exposure of the treated area to intense cold or heat such as sun lamps or sun bathing.
Will I need more than one treatment to achieve the desired result? You should discuss your treatment goals and plan with your doctor. If you are not satisfied with the treatment effect, you may need a touch‐up treatment to achieve the desired result.
Will the results of treatment last forever?
No. While individual results may vary, in the clinical study setting, results lasted up to 6 months in 58 out of 100 people treated with Restylane Silk. After this, re treatment may be needed to maintain your desired results.
User Assistance Information
Your questions about Restylane Silk can be personally answered by contacting the Galderma Laboratories, L.P. toll‐free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday through Friday.
1‐855‐425‐8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised: June 2023
Restylane Lyft
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane® Lyft with Lidocaine is a sterile gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically cross-linked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 and concentration of 20 mg/mL with 0.3% lidocaine.
Indication
Restylane® Lyft with Lidocaine is indicated for implantation into the deep dermis to superficial subcutis for the correction of moderate to severe facial folds and wrinkles, such as nasolabial folds.
Restylane® Lyft with Lidocaine is indicated for subcutaneous to supraperiosteal implantation for cheek augmentation and correction of age-related midface contour deficiencies in patients over the age of 21.
Restylane® Lyft with Lidocaine is indicated for injection into the subcutaneous plane in the dorsal hand to correct volume deficit in patients over the age of 21
How Supplied
Restylane® Lyft with Lidocaine is supplied in a disposable glass syringe with a luer-lock fitting. Restylane® Lyft with Lidocaine is co-packed with sterilized needle(s) as indicated on the carton, either 27 G Thin Wall (TW) x ½”, or 29 G TW x ½”.
A patient record label is a part of the syringe label. Remove it by pulling the flap marked with three small arrows. This label is to be attached to patient records to ensure traceability of the product.
The contents of the syringe are sterile.
The volume in each syringe and needle gauge is as stated on the syringe label and on the carton.
Self Life and Storage
Restylane® Lyft with Lidocaine must be used prior to the expiration date printed on the package.
Store at a temperature of up to 25°C (77°F). Do not freeze. Protect from sunlight. Refrigeration is not required.
Do not resterilize Restylane® Lyft with Lidocaine as this may damage or alter the product.
Do not use if the package is damaged or if expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
Contraindications
- Restylane® Lyft with Lidocaine is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane® Lyft with Lidocaine contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- Restylane® Lyft with Lidocaine is contraindicated for patients with bleeding disorders.
- Restylane® Lyft with Lidocaine is contraindicated for patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
Warnings
- Defer use of Restylane® Lyft with Lidocaine at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
- Injection site reactions (e.g., swelling, erythema, bruising, itching, tenderness, or pain) to Restylane® Lyft with Lidocaine have been observed as consisting mainly of short-term minor or moderate inflammatory symptoms starting early after treatment and generally with less than 2 weeks duration. Refer to the Adverse Experiences section for details.
- Restylane® Lyft with Lidocaine must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabella area. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Introduction of Restylane® Lyft with Lidocaine into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
- Special care should be taken to avoid injection into veins or tendons in the hand. Injection into tendons may weaken tendons and cause tendon rupture. Injection into veins may cause embolization or thrombosis.
- Injection into the hand may cause adverse events that last for more than 96 days. In a clinical study, 24.7% of subjects had at least a 10 degree negative change in thumb flexion which persisted through the course of the 6-months duration study. Refer to adverse events sections for additional details.
- Injection of the dorsum of the hand may cause pain in extremity and peripheral swelling.
- Injection of Restylane Lyft in the hand and post-treatment behavior such as strenuous use or trauma to the hands may increase the risk for delayed onset AEs in the hand.
Precautions
- Restylane® Lyft with Lidocaine is packaged for single patient use. Do not resterilize. Do not use if package is opened or damaged.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- For the treatment of moderate to severe facial wrinkles and folds, the maximum recommended dose per treatment is 6.0 mL based on U.S. clinical studies. For cheek augmentation implantation and the treatment of age-related midface volume deficit in patients over the age of 21 the maximum recommended dose is also 6.0 mL per treatment. For the treatment of dorsal hand volume deficit, the maximum recommended dose per hand is 3.0 mL based on U.S. clinical studies. The safety of injection greater amounts has not been established.
- Cheek augmentation or correction of age-related midface contour deficiencies in patients over the age of 21,with Restylane® Lyft with Lidocaine should only be performed by physicians who have appropriate experience and who are knowledgeable about the anatomy and the product for use in deep (subcutaneous and/or supraperiosteal) injection for cheek augmentation.
- Correction of volume deficit in the dorsal hand in patients over the age of 21, with Restylane® Lyft with Lidocaine should only be performed by physicians who have appropriate experience and who are knowledgeable about the anatomy and the product for use in the subcutaneous plane.
- Safety of Restylane® Lyft with Lidocaine injected into the dorsum of the hand in patients under 22 years old has not been studied.
- The safety or effectiveness of Restylane® Lyft with Lidocaine for the treatment of anatomic regions other than nasolabial folds, midface area and dorsal hand has not been established in controlled clinical studies.
- The safety and effectiveness of cannula injection of Restylane ® Lyft with Lidocaine for cheek augmentation and correction of age-related midface contour deficiencies have only been clinically evaluated in three brands of blunt-tip cannulas (DermaSculpt, Softfil, and TSK Steriglide) that were 25G-27G and 1.5 or 2 inches in length.
- Long term safety and effectiveness of Restylane® Lyft with Lidocaine beyond one year have not been investigated inclinical trials.
- As with all transcutaneous procedures, Restylane® Lyft with Lidocaine implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety and efficacy of Restylane® Lyft with Lidocaine for lip augmentation has not been established in controlled clinical studies.
- The safety of Restylane® Lyft with Lidocaine for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
- Formation of keloids may occur after dermal filler injections including Restylane® Lyft with Lidocaine ®. Keloid formation was not observed in studies involving 709 patients (including 160 African-Americans and 76 other patients of Fitzpatrick Skin Types IV, V and VI). For additional information please refer to Studies MA-1400-02, MA-1400-01, 31GE0002, 31GE0101, and MA-1400-05 in the Clinical Trials Section. In study MA-1400-03 with Restylane® Lyft with Lidocaine and Perlane®, there were 51.7% (31/60) of patients with Fitzpatrick Skin Types IV, V, and VI and no reports of keloid formation.
- Restylane® Lyft with Lidocaine injection may cause hyperpigmentation at the injection site. In a clinical study (MA—1400-01) of 150 patients with pigmented skin (of AfricanAmerican heritage and Fitzpatrick Skin Types IV, V, and VI), the incidence of postinflammatory hyperpigmentation was 6% (9/150). 50% of these events lasted up to six weeks after initial implantation. In study MA-1400-03 with Perlane® and Restylane® Lyft with Lidocaine, there were 51.7% (31/60) of patients with Fitzpatrick Skin Types IV, V, and VI and no reports of hyperpigmentation. In study MA-1400-05 with Restylane® Lyft with Lidocaine, there were 30.5% (61/200) of patients with Fitzpatrick Skin Types IV, V, and VI and no reports of hyperpigmentation.
- Injection of Restylane® Lyft Lidocaine in patients with pre existing tendency toward edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up.
- Injection of Restylane® Lyft Lidocaine too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable lumps.
- Restylane, ® Lyft with Lidocaine should be used with caution in patients on immunosuppressive therapy.
- Use of Restylane® Lyft with Lidocaine in dorsal hand in patients with diseases, injuries or disabilities of the hand has not been studied. Care should be used in treating patients with autoimmune disease affecting the hand, hand implants, Dupuytren’s contracture, history of hand tumor, vascular malformations, Raynaud’s disease and patients at risk for tendon rupture.
- Bruising or bleeding may occur at Restylane® Lyft with Lidocaine injection sites. Restylane® Lyft with Lidocaine should be used with caution in patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the preceding 3 weeks.
- Avoid injecting Restylane® Lyft with Lidocaine into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane® Lyft with Lidocaine into an area where an implant other than hyaluronic acid has been placed.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures at least until any initial swelling and redness has resolved.
- If epilation, UV irradiation or laser treatment, mechanical or chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane® Lyft with Lidocaine, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane® Lyft with Lidocaine is administered before the skin has healed completely after such a procedure.
- Injection of Restylane® Lyft with Lidocaine into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics e.g., certain anti arrhythmics, since the systemic toxic effects can be additive.
- Lidocaine should be used cautiously in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction.
- Individual variation and treatment area may affect the bio-degradation of Restylane® Lyft with Lidocaine, in rare cases product remnants has been detected in tissue when the clinical effect has returned to baseline.
- Restylane® Lyft with Lidocaine is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Galderma Laboratories, L.P. at 1-855-425-8722.
- Glass is also subject to breakage under a variety of unavoidable conditions. Care should be taken with the handling of the glass syringe and with disposing of broken glass to avoid laceration or other injury. After use, syringes and needles/blunt cannula should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state, and federal requirements.
- Restylane® Lyft with Lidocaine should not be mixed with other products before implantation of the device.
- The safety or effectiveness of Restylane® Lyft with Lidocaine for the correction of moderate to severe facial folds and wrinkles, such as nasolabial folds and for correction of volume deficit in the dorsal hand, with a small bore, blunt tip cannula has not been established in controlled clinical studies.
Adverse Experiences
Restylane® Lyft with Lidocaine is indicated for implantation into the deep dermis to superficial subcutis for the correction of moderate to severe facial folds and wrinkles, such as nasolabial folds and for subcutaneous to supraperiosteal implantation for cheek augmentation and correction of agerelated midface contour deficiencies in patients over the age of 21. It is also indicated for injection into the subcutaneous plane in the dorsal hand to correct volume deficit in patients over the age of 21.
Adverse event information for Restylane® Lyft with Lidocaine use in the correction of moderate to severe facial folds and wrinkles, such as nasolabial folds is presented in Tables 1-10 and for cheek augmentation and correction of age-related midface contour deficiencies is presented in Tables 11-13. Adverse event information for Restylane® Lyft with Lidocaine using a small bore, blunt-tip cannula for subcutaneous to supraperiosteal implantation for cheek augmentation and correction of age-related midface contour deficiencies in patients over the age of 21 is presented in Tables 14 16. Adverse event information for Restylane Lyft with Lidocaine use in the dorsal hand to correct volume deficit is presented in Tables 17-18.
Restylane® Lyft with Lidocaine for the correction of moderate to severe facial folds and wrinkles, such as nasolabial folds. There were five US studies that reported adverse events in support of the indication for treatment of moderate to severe facial folds and wrinkles, such as nasolabial folds. In two U.S. studies (i.e., Study MA-1400 01 and Study MA-1400-02) involving 433 patients at 25 centers, the adverse outcomes reported in patient diaries during 14 days after treatment are presented in Tables 1–4. The physician diagnosed adverse events identified in these studies at 72 hours after injection are presented in Table 7. In Study MA-1400-01, 150 patients were injected with Perlane® on one side of the face and Restylane® on the other side of the face. In study MA1400-02, 283 patients were randomized to receive either Perlane® or Restylane® injection on both sides of the face. Table 8 presents all investigator-identified adverse events recorded at study visits 2 weeks or more after injection in studies MA-1400-01, MA-1400-02, 31GE0101 and 31GE0002.
In Study 31GE0101, 150 Canadian patients were injected with both Perlane® and Hylaform®. In Study 31GE0002, 68 Scandinavian patients underwent both Perlane® and Zyplast® injections. In a fifth U.S. study (Study MA-1400-03) 60 patients at three centers randomly received Restylane® Lyft with Lidocaine injections on one side of the face and Perlane® injections on the other side of the face. The adverse events reported in patient diaries during 14 days after treatment are presented in Tables 5 and 6. The physician-recorded adverse events identified in study MA-1400-03 at 14 days after injection are presented in Table 9
Directions For Assembly
For safe use of Restylane® Lyft with Lidocaine, it is important that the needle is properly assembled.
Syringe with white cap:
Use your thumb and forefinger to hold firmly around both the syringe barrel and the luer lock adapter part (C) of the closure system.
With your other hand, take hold of the white cap (A) at the end of the closure system and gently tilt back and forth carefully until cap disconnects and can be pulled off (seal will be broken).
Do not rotate.
Do not touch the syringe tip (B) to keep it sterile.
Syringe with transparent cap:
Unscrew the tip cap of the syringe carefully
Assembly Of Needle To Syringe
Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the luer-lock adapter (C). Grasp the needle shield with the other hand. To facilitate proper assembly, both push and rotate firmly clockwise. Make sure the needle is screwed on all the way so that the needle shield touches the luer-lock adapter (C). To remove the needle shield, hold the syringe and the luerlock adapter. With your other hand hold the needle shield and pull straight out. Do not rotate
Pre-Treatment Guidlines
Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John’s Wort, or high doses of Vitamin E supplements. These agents may increase bruising and bleeding at the injection site.
Treatment Procedures
1. It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the Restylane® Lyft with Lidocaine treatment.
a. Advise the patient of the necessary precautions before commencing the procedure.
b. A consent form should be utilized.
2. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block.
3. The patient’s face or hands should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
4. Sterile gloves are recommended while injecting Restylane® Lyft with Lidocaine.
5. Before injecting, press plunger rod carefully until a small droplet is visible at the tip.
6. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify that the needle is not intravascular.
7. Restylane® Lyft with Lidocaine is administered using a thin gauge needle in the nasolabial folds. For cheek augmentation and the correction of age related midface contour deficiency, a thin gauge needle or a blunt tip cannula (recommended cannula gauge sizes 25-27G with 54 (57) cannula length of 1.5 or 2 inches) can be used. Restylane® Lyft with Lidocaine is supplied with 29 G TW x ½" needles or 27 G TW x ½" needles. The physician should use at their discretion the appropriate needle depending on the intended use of the product. When using a needle, the needle is inserted at an approximate angle of 30º parallel to the length of the wrinkle or fold. Restylane® Lyft with Lidocaine should be injected into the deep dermis to superficial layer of the subcutis for the treatment of moderate to severe facial folds and wrinkles (such as nasolabial folds) and for subcutaneous to supraperiosteal implantation for cheek augmentation and correction of age-related midface contour deficiencies in patients over the age of 21. If Restylane® Lyft with Lidocaine is injected too superficially this may result in visible lumps and/or bluish discoloration. When using a cannula for cheek augmentation and the correction of age related midface contour deficiency, after preparation as described above, an entry point is made in the skin with an incision needle of appropriate size. Inject slowly.
8. When treating the dorsal hand, Restylane® Lyft with Lidocaine can be administered using the supplied needles. With the needle, small boluses should be inserted in the dorsum of the hand in the subcutaneous plane. Small bolus injections or the linear retrograde injection technique can be used to deposit small volumes as needed. Rapid flow or rapid injection should be avoided.
9. Inject Restylane® Lyft with Lidocaine applying even pressure on the plunger rod. It is important that the injection is stopped just before the needle/cannula is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin. Do not apply excessive pressure to the syringe at any time. If resistance is encountered, the needle/ cannula should be partially withdrawn and repositioned, or fully withdrawn and checked for function and replaced if needed.
10. Only correct to 100% of the desired volume effect. Do not overcorrect. With cutaneous deformities the best results are obtained if the defect can be manually stretched to the point where it is eliminated. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue and the injection technique.
11. For the treatment of moderate to severe facial wrinkles and folds, the maximum
recommended dose per treatment is 6.0 mL based on U.S. clinical studies. For the treatment of age-related midface volume deficit, the maximum recommended dose is also 6.0 mL per treatment. For the treatment of volume deficit in the dorsal hand, the maximum recommended dose per hand is 3.0 mL per treatment. The safety of injecting greater amounts has not been established.
Injection Technique
1. Restylane® Lyft with Lidocaine can be injected by a number of different techniques that depend on the treating physician’s experience and preference, and patient characteristics.
2. Serial puncture (only recommended for needle) (A) involves multiple, closely spaced injections along wrinkles or folds. Although serial puncture allows precise placement of the filler, it produces multiple puncture wounds that may be undesirable to some patients.
3. Linear threading (B) is accomplished by fully inserting the needle/cannula into the middle of the wrinkle or fold and injecting the filler along the track as a “thread.” Although threading is most commonly practiced after the needle/cannula has been fully inserted and is being withdrawn, it can also be performed while advancing the needle/cannula (“push-ahead” technique).
4. Serial threading is a technique that utilizes elements of both approaches.
5. Cross-hatching (C) consists of a series of parallel linear threads injected at intervals of five to ten mm followed by a new series of threads injected at right angles to the first set to form a grid. This technique is particularly useful in facial contouring when coverage of the treatment region needs to be maximized.
A. Serial Puncture (only recommended for needle)
B. Linear Threading
C. Cross-hatching
6. Note! The correct injection technique is crucial for the final result of the treatment. Dissection of the sub-epidermal plane with lateral movement of the needle, rapid flows (>0.3 mL/min), rapid injection or high volumes may result in an increase in short-term episodes of bruising, swelling, redness, pain, or tenderness at the injection site.
7. It is recommended to change needle/cannula for each new treatment site.
8. When the injection is completed for the treatment of moderate to severe facial wrinkles and folds or age-related midface volume deficit, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area firmly between your fingers or against an underlying superficial bone to obtain optimal results. When the injection is completed for the treatment of the dorsal hand, the hand should be balled into a fist and a lubricating agent, such as ultrasound gel or petrolatum ointment should be applied. A deep thorough massage should be performed to smooth out the filler and push product into any remaining valleys or voids.
9. If so called “blanching” is observed, i.e., the overlying skin turns a whitish color, the injection should be stopped immediately and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with the American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection 1
10. If the wrinkle, midface or dorsal hand needs further treatment, the same procedure should be repeated until a satisfactory result is obtained. Additional treatment with Restylane® Lyft with Lidocaine may be necessary to achieve the desired correction.
11. If the treated area is swollen directly after the injection, an ice pack can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
12. Patients may have mild to moderate injection site reactions, which typically resolve in a few days.
Sterile Needles
- Follow national, local or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided.
- Discard unshielded needles in approved sharps collectors.
- Restylane® Lyft with Lidocaine is provided with a needle that does not contain engineered injury protection. Administration of Restylane® Lyft with Lidocaine requires direct visualization and complete and gradual insertion of the needle making engineered protections infeasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane® Lyft with Lidocaine?
Restylane® Lyft with Lidocaine is a clear injectable gel composed of hyaluronic acid, a natural substance that already exists in the body. Restylane® Lyft with Lidocaine is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. Restylane® Lyft with Lidocaine is non-animal-based and free from animal protein. Allergy pretesting is not necessary. Restylane® Lyft with Lidocaine also contains 0.3% lidocaine. The lidocaine in Restylane® Lyft with Lidocaine has been added to reduce the discomfort associated with the treatment.
How does Restylane® Lyft with Lidocaine work?
Restylane® Lyft with Lidocaine is injected into the skin with an ultrafine needle to plump the skin to smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth and is injected with an ultrafine needle or a small, blunt tipped cannula to increase the fullness of your cheeks. Restylane Lyft with Lidocaine may also be injected, using an ultrafine needle under the skin to address volume deficiency in the back of the hand.
Why is there lidocaine in Restylane® Lyft with Lidocaine?
The lidocaine in Restylane® Lyft with Lidocaine reduces pain and discomfort during and after injection. The effectiveness of the lidocaine was studied in a split-face clinical study of 60 patients. Each patient received Restylane® Lyft without Lidocaine on one side of the face and Restylane® Lyft with Lidocaine on the other side of the face for the treatment of lines around the nose and mouth. Restylane® Lyft with Lidocaine significantly reduced the pain of the injection.
- For the side of the face treated with Restylane® Lyft without Lidocaine, patients rated their pain as about 47 on a scale of 0 to 100 after injection.
- For the side of the face treated with Restylane® Lyft with Lidocaine, patients rated their pain as about 15 on the same scale.
- Pain relief from the lidocaine in Restylane® Lyft with Lidocaine lasted up to 60 minutes after treatment.
How long does Restylane® Lyft with Lidocaine last?
- When Restylane® Lyft with Lidocaine is used for the treatment of wrinkles and olds such as the lines from your nose to the corners of your mouth, the benefits generally last about 6 months as the filler gradually disappears from the body.
- When Restylane® Lyft with Lidocaine is used to increase the fullness of your cheeks, the benefits generally last between two and twelve months as the filler gradually disappears from the body. The graph below compares patients who were treated with Restylane Lyft with Lidocaine using a needle and patients who had no treatment, who showed a positive treatment response at 2, 4, 6, 8, 10 and 12 months, as assessed by blinded evaluators (e.g., physicians not aware of the patient treatment assignment).
Safety
Are there any reasons why I should not use Restylane® Lyft with Lidocaine? (Contraindications)
To ensure a safe procedure, your doctor will talk to you about your medical history to determine if you are an appropriate candidate for treatment. You should not use Restylane® Lyft with Lidocaine if:
- You have severe allergies with a history of severe reactions (anaphylaxis). An injection of Restylane® Lyft with Lidocaine may result in an allergic reaction.
- You are allergic to lidocaine or to any of the proteins used to make the hyaluronic acid in Restylane® Lyft with Lidocaine (bacterial proteins). An injection of Restylane® Lyft with Lidocaine may result in an allergic reaction.
- You are prone to bleeding or have been diagnosed with a bleeding disorder. An injection of Restylane® Lyft with Lidocaine may have a higher risk of severe bleeding or bruising. If you are not sure about your medical history concerning these allergies, please discuss further with your doctor.
Are there other warnings or precautions that I should discuss with my doctor?
Warning: One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately. There are several other important precautions to discuss with your doctor to ensure a satisfactory result and to avoid any complications. Please be sure to discuss the following with your doctor:
- Which areas of the face you would like to have treated
o Restylane® Lyft with Lidocaine is intended for use in the areas around the nose, mouth, and cheeks. Results have not been studied in other areas of the face in the United States.
o The use of Restylane® Lyft with Lidocaine on gel injection sites with skin sores, pimples, rashes, hives, cysts, or infections should be postponed until healing is complete. Use of Restylane® Lyft with Lidocaine in these areas of skin could delay healing or make your skin problems worse. - If you would like to have treatment in the hands
o Tell your doctor if you have had previous hand surgery including sclerotherapy or history of hand trauma.
o History of Raynaud’s disease or Raynaud’s phenomenon, or history of other disease - If you are of appropriate age to receive Restylane® Lyft with Lidocaine
o For injections around the nose and mouth, the safety of Restylane® Lyft with Lidocaine has not been studied in people younger than 18 years or older than 65 years.
o For injections to the cheek and hands, safety has not been studied in patients younger than 22 years. - If you are breastfeeding, pregnant, or trying to become pregnant
o The safety of Restylane® Lyft with Lidocaine for use during pregnancy, or in women who are breastfeeding, has not been studied. - If you are on any medications to decrease your body’s immune response (immunosuppressive therapy)
o Use of these medications may increase your risk of infection. - If you are using any “blood thinners” such as aspirin, warfarin, or any other medications that affect bleeding
o Using these medications may increase your risk of bruising or bleeding at the gel injection site. - If you have any history of scarring, particularly thick and stiff scars, or any skin color (pigmentation) disorders. These side effects can occur with hyaluronic acid fillers in general
o In clinical trials of Restylane® Lyft with Lidocaine, some African-American patients experienced a darkening of skin tone (hyperpigmentation) that resolved after 6 weeks.
o No excessive scarring (keloids) was reported by clinical trial patients across different skin tones (pale to dark). If you have any additional questions about any topic in this section, please discuss further with your doctor.
What are possible side effects after an injection of Restylane® Lyft with Lidocaine?
It is important to understand that any procedure carries a risk of side effects. An injection of dermal filler can have two sources of skin reactions: from the injection itself and from the dermal filler.
Based on the clinical trials, you may experience skin discoloration (bruising), swelling, redness, tenderness, pain, itching, or small bumps in the area where you are injected as well as a headache. If any of these side effects occur, the majority are mild to moderate reactions that disappear within a week or two. If any symptom lasts longer than 2 weeks, you should call your doctor. In a clinical study on cheek injections using a needle, 3 people out of 100 (3%) had the following delayed injection site reactions up to 138 days after treatment:
- Redness
- Bruising
- Inflammation
- Bumps
- Pain
- Swelling
- Warmth
- Hardening
What are some potential risks that I may encounter?
Other potential risks may arise from an injection of a dermal filler such as Restylane® Lyft with Lidocaine including the following:
- Infection - Facial skin injections, including those with Restylane® Lyft with Lidocaine, are associated with a risk of infection. As with any infection, there may be a need for your doctor to prescribe antibiotics. Though rare, a skin infection could appear as small, swollen (or red) bumps (inflammatory papules). If an infection worsens over time, you should contact your doctor for further treatment.
- Scarring - While it is very rare, scarring may occur with an injection procedure. In clinical trials, excessive scarring (keloids) was not observed in any of the patients receiving Restylane® Lyft with Lidocaine.
- Change in skin tone - If you are African American, you may have a higher risk of darkening of the skin tone in the treated area (hyperpigmentation). This may take several weeks to disappear. In clinical trials, this change in skin tone did not occur with injection of Restylane® Lyft with Lidocaine into the cheeks.
- Cold sores - If you have had cold sores in the past, there is a risk that they will return as a result of facial injections.
- Age and pregnancy - If you are under 18 or over 65 years of age, are pregnant or trying to become pregnant, or are nursing, you should know that the safety and effectiveness of Restylane® Lyft with Lidocaine has not been established in patients like yourself. In addition, for treatment of the cheeks, Restylane® Lyft with Lidocaine has not been evaluated in patients younger than 22 years of age.
- Vision changes - Rarely, vision abnormalities have been reported after treatment with Restylane® Lyft with Lidocaine. 7 (14)
- Use of other skin therapies - The safety of Restylane® Lyft with Lidocaine used with other skin therapies such as laser, mechanical or chemical peeling, and hair removal has not been established. The use of Restylane® Lyft with Lidocaine with these skin therapies may lead to other side effects such as inflammation.
- Ultraviolet (UV) exposure - You should avoid exposing the area(s) treated with Restylane® Lyft with Lidocaine to excessive sun, UV lamps or indoor tanning beds/booths, and extreme heat and cold until any redness or swelling has disappeared. Exposure to UV sources may result in irritation at the site of treatment.
- Thumb Function – You may experience a slight decrease in the flexibility of your thumb after treatment with Restylane® Lyft with Lidocaine in the back of your hand. If you have any additional questions or concerns about these potential risks, please discuss them with your doctor.
What were the side effects reported by patients in the clinical trials?
After the injection, most patients reported redness, swelling, bruising, lumps/bumps, pain/tenderness, or itching at the gel injection site. Most side effects were mild and short-lived, did not require medical attention, and disappeared within 1 to 2 weeks. In addition, the lidocaine (anesthetic) in Restylane® Lyft with Lidocaine significantly reduced pain during and after treatment. Table 3 below shows what patients reported in their trial diaries after injection of Restylane® Lyft with Lidocaine to treat wrinkles and folds around the nose and mouth.
In a clinical study of 200 patients for the treatment of cheek fullness with Restylane® Lyft with Lidocaine using a needle, patients were asked to score the duration of pain, tenderness, redness, bruising, swelling, and itching. Table 4 below shows what patients reported in their trial diaries during this study. Bruising lasted longer than other side effects, and within 2 weeks most events had resolved.
In a clinical study of 89 patients for the treatment of volume loss in the dorsal hand with Restylane® Lyft with Lidocaine, patients were asked to score the duration of pain, tenderness, redness, bruising, swelling, itching, and impaired hand function.
Table 5 below shows what patients reported in their trial diaries during this study after initial treatment, and Table 6 shows in detail for how long each symptom lasted. Table 5. Side effects after initial treatment, as reported in Patient Diaries Side effect
Experienced by Remaining after one week in Swelling 75 out of 100 people (75%) 9 out of 100 people (9%) Tenderness 74 out of 100 people (74%) 14 out of 100 people (14%)
Redness 71 out of 100 people (71%) None
Bruising 60 out of 100 people (60%) 2 out of 100 people (2%)
Pain 45 out of 100 people (45%) 3 out of 100 people (3%)
Itching 13 out of 100 people (13%) None
Impaired function 7 out of 100 people (7%) None
Table 6. Duration of Patient Reported Symptoms after initial treatment Total number of patients with this symptom
Number of patients With Symptoms at specified Time
Intervals (Days)
1
n (%)
2 – 7
n (%)
8 – 14
n (%)
15 – 21
n (%)
22 – 27
n (%)
Pain 40 19 (47.5%) 20 (50%) none none 1 (2.5%)
Tenderness 66 15 (22.7%) 42 (63.6%) 4 (6.1%) 2 (3.0%) 3 (4.5%)
Redness 63 27 (42.9%) 36 (57.1%) none none none
Bruising 53 13 (24.5%) 39 (73.6%) 1 (1.9%) none none
Swelling 67 17 (25.4%) 44 (65.7%) 5 (7.5%) 1 (1.5%) none
Itching 12 7 (58.3%) 5 (41.7%) none none none
Impaired Function 6 4 (66.7%) 2 (33.3%) none none none
n = the number of patients who experienced this reaction within the specified time interval
% = out of 100 people, the expected number of people who will experience this reaction for the number of days specified
Additionally, in the hand functionality testing after the treatment, 24.7% of subjects had a slight decrease in thumb flexion (bending their thumb) which remained throughout the 6-months study. However, for 10 of these 22 subjects, a decrease in the non-treated (fellow) hand was also observed.
In this study, one hand on each patient was injected with Restylane Lyft with Lidocaine at the start of the study, 4 weeks later for a touch-up for some of the patients, and at a 6-month Retreatment for some of the patients. The other hand was injected with Restylane Lyft with Lidocaine for the first time at 6-months into the study (Initial Treatment) and 4 weeks later for a touch-up for some of the patients. Similar pattern of injection site reactions were found at all treatment occasions, i.e. the incidence of injection site reactions decreased over the first week, and within 2 weeks most events had resolved.
In a clinical study of 60 patients for the treatment of cheek fullness with Restylane® Lyft with Lidocaine using a cannula for injection, patients were asked to report if they had pain, tenderness, redness, bruising, swelling, and itching during the first 2 weeks after each treatment. Table 7 below shows what patients reported in their trial diaries during this study.
Table 7. Side effects after treatment for the cheeks as reported in patient diaries:
Restylane Lyft with Lidocaine using a cannula for injectiona 1st Treatmentb 2nd Treatment Side effect Experienced by Side effect Experienced by
Bruising 18 out of 60 people (30%) Bruising 11 out of 43 people (26%)
Redness 26 out of 60 people (43%) Redness 9 out of 43 people (21%)
Swelling 38 out of 60 people (63%) Swelling 27 out of 43 people (63%)
Pain 36 out of 60 people (60%) Pain 21 out of 43 people (49%)
Tenderness 55 out of 60 people (92%) Tenderness 31 out of 43 people (72%)
Itching 11 out of 60 people (18%) Itching 4 out of 43 people (9%) a
Clinical Study 43USC1633b
Based on 60 study patients who provided information about side effects after their 1st treatment c. Based on 43 study patients who provided information about side effects after their 2nd treatment about 4 months later.
What are the major side effects?
Rarely, the doctor may inadvertently inject the product into a blood vessel, which can cause injury to the blood supply and damage to the skin, or vision abnormalities including blindness. Rarely, a few people have developed infections that must be treated with antibiotics or other treatment (such as surgery). Infection may be hard to treat, but will generally go away when the gel is absorbed.
In clinical trials, 2 patients reported 4 serious adverse events (SAEs) that were considered to be related to the device and/or the procedure. One subject reported gel injection site swelling (late onset inflammatory reactions) in both cheeks at separate times. Treatments for the left and right cheeks each included antibiotics, NSAID nonsteroidal anti-inflammatory medications (such as ibuprofen and naproxen) and a medicine to help break down the Restylane® Lyft with Lidocaine so that it is more easily absorbed (hyaluronidase). The second patient experienced gel injection site bruising (hematoma) in the right cheek and gel injection site infection/abscess. Treatment of the right cheek infection/abscess and gel injection site bruising included antibiotics and a surgical procedure (incision and drainage). In the clinical trial for the hand, 4 patients with adverse events of swelling, small bump (nodules) , or tenderness that were considered to be related to the device and/or the procedure received treatments that included antibiotics, NSAID nonsteroidal anti-inflammatory medications (such as ibuprofen and naproxen) and medicine used to help breakdown HA in the body (hyaluronidase).
All events resolved with treatment and time.
What side effects have been voluntarily reported of Restylane Lyft with Lidocaine use in and outside of the United States?
The most common side effects included reports of transient swelling/oedema and inflammatory reactions with immediate onset or delayed onset, up to several weeks after treatment. The following events were also reported:
- Short duration of effect
- Hardening (mass/induration)
- Pain or tenderness
- Skin redness (erythema)
- Bruising (hematoma)
- Presumptive bacterial infections and pus (abscess formation)
- Small bumps (papules/nodules)
- Inflammation
- Injection site reactions including burning sensation, warmth and irritation
- Skin discoloration (hyperpigmentation)
- Reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia) and facial nerve paralysis
- Allergic reaction (hypersensitivity) and rapid swelling (angioedema)
- Restricted blood flow (ischemia/necrosis), eye pain, eye swelling, eye irritation, increased secretion of tears (increased lacrimation), drooping eyelid (eyelid ptosis) and visual impairment such as blurred vision, reduced visual acuity and blindness
- Itching (pruritus)
- Scarring
- Device displacement
- Rash
- Leakage from implant site (effusion/discharge)
- Small area of inflammation in tissue (granuloma)
- Acne
- Blisters/vesicles
- Symptoms of reactivation of herpes infection
- Hives (urticaria)
- Dilated small blood vessels (telangiectasia)
- Leakage of product from implant site (extrusion of device)
- Dermatitis
- Muscle disorders such as muscle twitching and muscle weakness
- Encapsulation of gel in the tissue
- Other dermatological events including dry skin, skin wrinkling, peeling of skin and localized hair loss (alopecia)
- Non-dermatological events including headache, discomfort (malaise), fever, dizziness, sinus infection, shortness of breath (dyspnea), feeling tired (fatigue), influenza like illness, insomnia, nausea and anxiety.
In rare cases after treatment in the cheeks, a late onset of side effects (weeks to months after treatment) and recurrent inflammation was reported. The symptoms were small bumps or lumps, infection, and skin redness, swelling and pain. Treatments of these events included a medicine used to help break down HA in the body (hyaluronidase), antibiotics, drugs to reduce inflammation (corticosteroids), drugs to relieve pain (analgesics) and surgical procedure (incision and drainage).
The most commonly reported serious adverse events were infection/pockets of pus (abscess), restricted blood flow leading to the death of skin (ischemia/necrosis), vision loss, allergic reactions (hypersensitivity), scarring, areas of inflammation in tissue (granuloma) including cases of hardening (mass/induration). Other serious events included common related symptoms such as; swelling, pain/tenderness, skin redness (erythema), reduced sense of touch (hypoaesthesia), tingling sensation (paraesthesia), bruising, skin discoloration , small bumps (papules/nodules), and overcorrection, overfill and irregular skin.
- Serious infection and abscess (pus) were reported with a time to onset from one day to two months following the injection. Most of the patients were recovered or recovering at the time of last contact. The treatments included antibiotics, drugs to relieve pain (analgesics), drugs to reduce inflammation (corticosteroids) and hyaluronidase (a medicine to help break down the Restylane® Lyft with Lidocaine so that it is more easily absorbed).
- Serious allergic reactions (hypersensitivity) were reported in most cases with a time to onset ranging from immediately to few weeks post injection. Most of the events were recovered or recovering at the time of last contact. The treatments included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines), antibiotics, and drugs to reduce inflammation (corticosteroids).
- Serious small area of inflammation in tissue (granuloma), including hardening, were reported with a time to onset ranging from one day to a year or longer. The outcomes were mostly recovered or recovering at the time of last contact. Treatment included drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamines,) antibiotics, drugs to reduce inflammation (corticosteroids) and surgical removal (excisions). Incisions to examine tissue (biopsies) have been taken in some cases, but the majority of cases are non-biopsy confirmed.
- Serious inflammation was reported with a time to onset from one to two weeks post injection. Most events were recovered or recovering at the time of last contact. Rare cases of inflammation with delayed onset up to several weeks or months post injection has been observed; particularly if the patient experienced local trauma, facial/dental infection, or local infection. The treatment included drugs to relieve pain (analgesics), antibiotics, and corticosteroids.
- Blockage of a blood vessel (vascular occlusion) resulting in restricted blood flow and vision disturbances including blindness have been reported following injection of any soft tissue filler in the face especially in the nose, between the eyebrows (glabella), around the eyes (periorbital areas), smile lines (nasolabial folds) and cheek, with a time to onset ranging from immediate to a few weeks following injection. This may appear as whitening of the skin (blanching), skin discoloration, death of skin (necrosis) or ulceration at the implant site or in the area supplied by the blood vessels affected; or rarely as restriction in blood supply to tissues (ischemic events) in other organs due to blocked blood vessels (embolization). Isolated rare cases of restriction in blood supply to tissues (ischemic events) affecting the eye leading to visual loss, and the brain resulting in stroke (cerebral infarction), following facial aesthetic treatments have been reported. Reported treatments include medicine to prevent blood clotting (anticoagulant), medicine to treat allergic reactions (epinephrine), aspirin, a medicine to help break down HA in the body (hyaluronidase), drugs to reduce inflammation (corticosteroid treatment), drugs to relieve pain (analgesics), antibiotics, local wound care, drainage, hyperbaric oxygen and surgery. Outcome of the events ranged from resolved to ongoing at the time of last contact.
- Gel injection site bruising, swelling, skin redness and pain mostly non-serious generally occurred on the same day as treatment usually resolving within 1 to 4 weeks. Some occurrences have persisted for up to 6 months. Most instances of discoloration including darkening skin tone (hyperpigmentation), sometimes described as a blue or brown color, have occurred within the same day as treatment but have also occurred up to 6-months post treatment. These events typically resolve within a few days but with some infrequent instances lasting up to 18 months.
- If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
- Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Troubleshooting
When should I call my doctor? What should I call my doctor about after the treatment?
Most side effects like bruising, swelling, pain, tenderness, redness, and itching will usually go away within 2 weeks. Call your doctor if you have persistent problems beyond 14 days.
You can develop an infection that should be treated with antibiotics. If it gets worse, you may need other treatments, such as surgery. If you experience redness, tenderness, and pain that do not go away in 2 weeks, you should call your doctor. Blisters or skin sores that recur may signal the presence of a herpes infection that must be treated. Seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure (http://www.nlm.nih.gov/medlineplus/stroke.html).
Administration
What should I do before treatment?
Restylane® Lyft with Lidocaine requires no allergy pretesting. However, before you undergo treatment with Restylane® Lyft with Lidocaine, you should take the following precautions:
- Avoid using the following products, because these may increase bruising or bleeding at the gel
injection site:
o St. John’s Wort
o High doses of vitamin E supplements
o NSAID Nonsteroidal anti-inflammatory medications (such as aspirin or ibuprofen)
If you have previously suffered from facial cold sores, discuss this with your doctor. Your doctor may consider prescribing a medication to minimize recurrences.
What is the dose of Restylane® Lyft with Lidocaine?
The amount used depends on your face or hands and what you would like to have treated. The average patient who has all of the severe wrinkles around the mouth corrected will use less than half a tablespoon. Most patients getting Restylane® Lyft with Lidocaine for the fullness of cheeks may require a larger dose. Based on U.S. clinical studies, the recommended dose per treatment should not exceed 6.0 mL in the face and 3.0 mL per hand.
Do the injections hurt?
As with all injections, there may be pain or discomfort during the procedure. Restylane® Lyft with Lidocaine contains lidocaine, a local anesthetic, to reduce the pain or discomfort associated with an injection. In addition, Restylane® Lyft with Lidocaine is injected directly into the skin in tiny amounts by an ultrafine needle. To help maximize your comfort, you should discuss the use of numbing medicines with your doctor before treatment.
Post Marketing Surveillance
What are possible side effects after an injection of Restylane® Lyft with Lidocaine?
It is important to understand that any procedure carries a risk of side effects. An injection of dermal filler can have two sources of skin reactions: from the injection itself and from the dermal filler. Based on the clinical trials, you may experience skin discoloration (bruising), swelling, redness, tenderness, pain, itching, or small bumps in the area where you are injected as well as a headache. If any of these side effects occur, the majority are mild to moderate reactions that disappear within a week or two. If any symptom lasts longer than 2 weeks, you should call your doctor.
In a clinical study on cheek injections using a needle, 3 people out of 100 (3%) had the following delayed injection site reactions up to 138 days after treatment:
- Redness
- Bruising
- Inflammation
- Bumps
- Pain
- Swelling
- Warmth
- Hardening
Post-treatment Checklist
- Consider the following after treatment with Restylane® Lyft with Lidocaine:
Cold compresses (a cloth dipped in cold water, wrung out, and applied to the injected area) may be used immediately after treatment to reduce swelling. - Avoid touching the treated area within 6 hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- Avoid exposure of the treated area to intense heat (sun lamp or sun bathing) until there is no redness or swelling.
- If you have previously suffered from facial cold sores, there is a risk that the needle punctures could contribute to another occurrence. Speak to your physician about medicine to prevent this from happening again.
- Avoid taking aspirin, non-steroidal anti-inflammatory medications, St. John’s Wort, and high doses of vitamin E supplements for 1 week after treatment. These agents may increase bruising and bleeding at the gel injection site.
- After receiving treatment in the hands, avoid strenuous use of your hands as it may increase the risk for delayed onset adverse events.
User Assistance Information
Your questions about Restylane® Lyft with Lidocaine can be personally answered by contacting the Galderma Laboratories, L.P. toll-free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday through Friday.
1-855-425-8722
Galderma (logo)
Restylane® is a registered trademark of Galderma S.A. or its affiliates.
Revised: June 2023
Restylane Refyne
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane® Refyne is a sterile, biodegradable, viscoelastic, non-pyrogenic, clear, colorless, and homogeneous soft hyaluronic acid gel with a moderate lifting capacity. The product has a sodium hyaluronate concentration of 20 mg/mL in phosphate buffered saline at pH 7 and contains 3 mg/mL lidocaine hydrochloride.
Indication
Restylane Refyne is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds) in patients over the age of 21.
How Supplied
Restylane Refyne injectable gel is supplied in individual treatment syringes with needles as indicated on the carton. The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile. Do not resterilize. Do not use the product if package is open or damaged or if expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P
Self Life and Storage
Restylane Refyne must be used prior to the expiration date on the package. Store at a temperature of up to 25ºC/77ºF. Do not freeze. Protect from sunlight. Refrigeration is not required.
Restylane Refyne injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Galderma Laboratories, L.P. immediately at 1-855-425-8722
Contraindications
- • Restylane Refyne is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane Refyne may contain trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- Restylane Refyne contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- Introduction of Restylane Refyne into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Restylane Refyne must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Product use at sites in which an active skin disease is present, such as inflammation (skin eruption such as cysts, pimples, rashes or hives), infection, or tumors, in or near the intended treatment site should be deferred until the underlying process has been controlled.
For additional information please see the Post-Marketing Surveillance in Adverse Events.
Precautions
- Restylane Refyne is packaged for single-patient and single-session use only. Do not resterilize. Do not use if package is open or damaged.
- The safety and effectiveness for the treatment of anatomic regions other than the facial wrinkles and folds have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- Restylane Refyne is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 22 years has not been established.
- Injection of Restylane Refyne in patients with pre-existing tendency towards edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up.
- Injection of Restylane Refyne too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable
umps. - Restylane Refyne should be used with caution in patients on immunosuppressive therapy.
- Restylane Refyne should be used with caution in patients with bleeding disorders.
- Do not inject the product in close proximity to a site that has been treated with a permanent implant as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting into an area where an implant other than hyaluronic acid has been placed.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at treatment sites.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures at least until any initial swelling and redness has resolved.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane Refyne, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane Refyne is administered before the skin has healed completely after such a procedure.
- Injections of Restylane Refyne into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Inflammatory pigmentation changes and scarring might occur following dermal filler injections. Patients with abnormal wound healing or dark skin (Fitzpatrick Type IV-VI) may be more prone to develop hypertrophic scarring and keloid formation.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- Individual variation and treatment area may affect the bio-degradation of Restylane Refyne and product might be detected in the tissue even after the clinical effect has disappeared.
- Restylane Refyne injectable gel is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Galderma Laboratories, L.P. at 1-855-425-8722
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer lock and needle hub connection.
- Restylane Refyne contains lidocaine. If additional dental block or topical lidocaine or other local anesthetics or agents structurally related to amide-type local anesthetics are used concurrently with the product the following considerations should be observed:
- Use with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction
- High doses of lidocaine (more than 4.5 mg/kg of bodyweight) can cause acute toxic reactions manifesting as symptoms affecting the central nervous system and cardiac conduction.
- Systemic toxic effects could be additive
Adverse Experiences
A. Clinical Evaluation of Restylane Refyne One hundred seventy (170) subjects were enrolled in a randomized, double-blinded (subject and evaluator), active controlled, split-face comparison clinical trial to evaluate the safety and effectiveness of Restylane Refyne vs. a non-lidocaine-containing comparator. Touch-up treatments occurred approximately 3 weeks after initial injection, as needed, to achieve volume correction. After 48 weeks, subjects could opt for retreatment with Restylane Refyne to both sides of the face, with a subsequent touch-up as needed 3 weeks afterwards. One hundred twelve subjects (112, 65.9%) opted for retreatment. Preprinted diary forms were used by subjects for subject-reported assessments of specific signs and symptoms experienced during each of the first 21 days after initial, touch-up, and repeat treatments. Subjects rated each treatment site response as “Mild” “Moderate” “Severe” or “None.” Of the 170 subjects who received treatment, 98.8% (168 subjects) completed the diary forms. Of the 112 subjects who opted for retreatment, 97.3% (109) subjects completed the diary forms after retreatment.
After initial treatment, subjects rated pre-defined treatment site responses (redness, swelling, bruising, lump/bump formation, pain/tenderness, and itching) as predominantly mild or moderate in intensity (Table 1), typically with a duration of 1 to 2 weeks (Table 2). Based on data from 109 subjects, no increase in frequency or in intensity of signs/symptoms was observed following the retreatment injection or retreatment touch-up injection. The trend in adverse events remained the same across subject skin types. Among the 73 subjects of Fitzpatrick Skin Types IV, V, and VI (18 of which were of Skin Type V or VI) in the study, no cases of keloid formation or of hyperpigmentation were reported. Treatment site responses reported in subject diaries that lasted longer than 3 weeks were considered adverse events (AEs). AEs were also reported by the Treating Investigator at all follow-up visits where applicable. Among the 170 treated subjects, 7.1% (12/170) experienced device- and injection-related AEs following initial and touch-up treatment, as well as retreatment and touch-up treatment. These subjects reported a total of 9 events related to control treatment and 10 events related to Restylane Refyne. The most common of treatment site responses was injection site erythema, which was reported for 4 subjects. Other treatment site responses (swelling, mass, hematoma, pruritus, and anesthesia) were reported for 1 subject each. Other related adverse events included presyncope (2 subjects), headache (1 subject), syncope (1 subject), and ecchymosis (1 subject). Two subjects reported 2 serious adverse events (SAEs) that were considered to be unrelated to the device. The events were worsened knee osteoarthritis and a case of cholecystitis.
Treatment site responses after initial treatments are summarized by severity in Table 1 and by duration in Table 2.
Table 1 - Treatment Site Responses by Maximum Severity Occurring In Subjects After Initial Treatment
Restylane Refyne (N=170)
n (%)
Control (N=170)
n (%)
Mild Moderate Severe Total Mild Moderate Severe Total
Post-Initial Injectiona
(N= 168 for Restylane Refyne and N= 168 for the control)
Redness 60 (35.7) 24 (14.3) 9 (5.4) 93 (55.4) 62 (36.9) 22 (13.1) 14 (8.3) 98 (58.3)
Swelling 66 (39.3) 30 (17.9) 5 (3.0) 101 (60.1) 52 (31.0) 44 (26.2) 6 (3.6) 102 (60.7)
Bruising 49 (29.2) 29 (17.3) 18 (10.7) 96 (57.1) 51 (30.4) 31 (18.5) 14 (8.3) 96 (57.1)
Lump/Bump
Formation 39 (23.2) 26 (15.5) 10 (6.0) 75 (44.6) 45 (26.8) 27 (16.1) 11 (6.5) 83 (49.4)
Pain/Tenderness 58 (34.5) 11 (6.5) 3 (1.8) 72 (42.9) 65 (38.7) 19 (11.3) 2 (1.2) 86 (51.2)
Itching 21 (12.5) 3 (1.8) 1 (0.6) 25 (14.9) 28 (16.7) 1 (0.6) 0 29 (17.3)
Percentages are based on total number of subjects who reported local tolerability assessments in a subject diary.
a Number of subjects who completed subject diaries.
Table 2 - Duration of Treatment Site Responses Occurring In Subjects After Initial
Treatment
Injection site
response
Restylane Refyne (N=170)
n (%)
Control (N=170)
n (%)
Durationa 1-3 Days 4-7 Days 8-14 Days >14 Days 1-3 Days 4-7 Days 8-14 Days >14 Days
Post-Initial Injectionb
(N= 168 for Restylane Refyne and N= 168 for the control)
Redness 71 (42.3) 13 (7.7) 5 (3.0) 4 (2.4) 73 (43.5) 18 (10.7) 5 (3.0) 2 (1.2)
Swelling 58 (34.5) 23 (13.7) 14 (8.3) 6 (3.6) 55 (32.7) 24 (14.3) 17 (10.1) 6 (3.6)
Bruising 31 (18.5) 30 (17.9) 27 (16.1) 8 (4.8) 28 (16.7) 35 (20.8) 29 (17.3) 4 (2.4)
Lump/bump
Formation 33 (19.6) 19 (11.3) 9 (5.4) 14 (8.3) 34 (20.2) 21 (12.5) 16 (9.5) 12 (7.1)
Pain/tenderness 53 (31.5) 11 (6.5) 8 (4.8) 0 63 (37.5) 19 (11.3) 4 (2.4) 0
Itching 22 (13.1) 2 (1.2) 1 (0.6) 0 26 (15.5) 3 (1.8) 0 0
Percentages are based on total number of subjects who reported local tolerability assessments in a subject diary. a Number of days was defined as the sum of days when a sign/symptom was scored 'Mild' or higher. b Number of subjects who completed subject diaries.
Clinical Trials
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Directions For Assembly
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Assembly Of Needle To Syringe
Using surgical gloves, remove the cap from the needle and unscrew the tip cap from the syringe. Hold firmly around the syringe barrel and grasp the needle shield with the other hand. Screw the needle tight onto the syringe by simultaneously pushing and rotating firmly until the needle is completely locked. To ensure proper assembly, minimize the gap between the needle shield and the syringe. See he figure below.
Remove the needle shield just before injection by pulling it straight out. Do not rotate.
Note: Improper assembly may cause leakage or needle disconnection.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction. Pre-treatment photographs are recommended.
Treatment Procedures
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Injection Technique
1. Restylane Refyne is a cross-linked formulation resulting in a soft injectable gel that can be injected using a 30 G needle, for contouring and volumizing of facial wrinkles and folds.
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction. Pre-treatment photographs are recommended.
3. Although the study showed that lidocaine in Restylane Refyne had an effect on pain, supplementary anesthesia may be used for additional pain management during and after injection.
4. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic.
5. To avoid breakage of the needle, do not attempt to bend or otherwise manipulate it before or during treatment. If needle gets bent, discard it and complete the procedure with a replacement needle. Do not re-shield used needles. Recapping by hand is a hazardous practice and should be avoided. Discard unshielded needles in approved sharps collectors.
6. Before injection press the plunger rod carefully until a small droplet is visible at the tip of the needle.
7. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle. If resistance is encountered the needle should be partially withdrawn and repositioned or fully withdrawn and checked for function and replaced if needed.
8. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not in a blood vessel.
9. After the first small amount of material has been injected into the patient, wait a few seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
10. The injection technique, the depth of injection and volume administered may vary based on the subject’s treatment needs. A retrograde linear threading technique, serial puncture injections, or a combination of the 2 have been used to achieve optimal results. Injecting the product too superficially may result in visible lumps and/or bluish discoloration. It is recommended to change needle for each new treatment site.
11. Inject Restylane Refyne by applying even pressure on the plunger rod while slowly pulling the needle backward. It is important that the injection be stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
12. Injection volume to achieve optimal correction of moderate to severe nasolabial folds is generally about 1.5 mL per treatment site. Injection volume to achieve optimal correction for retreatment is generally about 1.0 mL per treatment site.
13. Correct to 100% of the desired volume effect. Do not overcorrect.
14. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
15. When injection is completed, the treated site may be gently massaged to mold the product to the contour of the surrounding tissue and assure that it is evenly distributed. If overcorrection occurs, massage the area between your fingers or against an underlying superficial bone to obtain optimal results.
16. With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of treatment. In these cases, it is better to invite the patient back to the office for a touch-up treatment.
17. Patients may experience treatment site responses, which typically resolve within 1 to 2 weeks. If the treated area is swollen directly after the injection, an ice pack with adequate protective cloth may be applied on the site for a short period following treatment to minimize swelling and reduce pain. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
18. The health care practitioner should instruct the patient to promptly report any problems associated with the use of Restylane Refyne.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane Refyne?
Restylane Refyne is a dermal filler injected under the (facial) skin. Once in place, it helps smooth away your “laugh lines” – the wrinkles and folds that may form at the sides of your nose and run down toward the corners of your mouth. Restylane Refyne is made out of hyaluronic acid ‐ a naturally occurring sugar, found in the body that gives the skin moisture, volume, and elasticity – and a small amount of lidocaine, which is a commonly used local anesthetic to numb the skin. Restylane Refyne is made using a manufacturing process called XpresHAn Technology™, which creates a smooth, injectable gel that can give your skin a natural, soft look.
3. INDICATIONS FOR USE
What is Restylane Refyne for?
As you age, your facial skin begins to lose its elasticity and volume. As a result, your “laugh lines”, the creases that run from the sides of your nose toward the corners of your mouth, become more pronounced. Restylane Refyne injectable gel is designed to temporarily help counter this by smoothing out these wrinkles and folds and restoring a natural, soft look to your face. Restylane Refyne has been shown to maintain this effect for up to 12 months.
Note: Facial features can differ. Speak to your doctor about the lines on your face that are appropriate for treatment with Restylane Refyne.
How is Restylane Refyne used?
Restylane Refyne is injected into the facial skin through a small needle to smooth facial wrinkles and folds (laugh lines), resulting in a more youthful appearance of the skin. For most patients, the procedure only takes 15 – 30 minutes.
4. CONTRAINDICATIONS
Are there any reasons why I should not receive Restylane Refyne?
Before using Restylane Refyne, your doctor will talk to you about your medical history to determine if you are an appropriate candidate for treatment. You will be asked questions about possible allergies to ensure that Restylane Refyne can be safely administered.
Tell your doctor about all of your medical conditions, including if you:
Have severe allergies with a history of severe reactions (anaphylaxis). Use of Restylane Refyne
may result in an allergic reaction.
Are allergic to the anesthetic lidocaine or to any of the proteins used to make the hyaluronic
acid in Restylane Refyne (bacterial proteins). Use may result in an allergic reaction.
If you are not sure about your medical history concerning these allergies, please discuss further with
your doctor.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
- Restylane Refyne helps treat laugh lines – the natural facial wrinkles and folds that can occur due to aging. Restylane Refyne has not been tested to treat any other types of wrinkles.
- If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your doctor immediately.
- You have had any prior surgery or procedures in the area you intend to be treated with Restylane Refyne.
- The use of Restylane Refyne if you have skin sores, pimples, rashes, hives, cysts, or infections should be postponed until healing is complete. Use of Restylane Refyne in these instances could delay healing or make your skin problems worse.
- Restylane Refyne is for adults ages 22 and older.
- The safety of Restylane Refyne has not been studied in women who are pregnant or breastfeeding. The risk of using Restylane Refyne in pregnant or breastfeeding women is unknown. Talk to your doctor before using Restylane Refyne if you are pregnant, planning to become pregnant, or breastfeeding.
- You may have a greater risk of developing an infection if you use Restylane Refyne while taking any medication that reduces your body’s natural defense system. These medications are called “immunosuppressants” because they stop your body’s immune system from functioning normally. Tell your doctor about any medication you are taking.
- Some medication like aspirin and warfarin can thin your blood, which may increase your risk of bleeding or prolong any bleeding that occurs. These medications also increase your risk of bruising or bleeding at the injection site. Tell your doctor about any medication you are taking.
- As with any injection procedure, you may have a higher risk of bruising or bleeding at the injection site if you have a bleeding disorder.
- If you have any history of scarring, particularly thick and stiff scars, or any skin color (pigmentation) disorders, talk to your doctor about this before your procedure. Scarring and skin color changes can occur with hyaluronic acid fillers in general. When Restylane Refyne was studied in patients with different skin tones (pale to dark), there were no reports by patients of excessive scarring (keloids) or changes in skin color.
- The use of Restylane Refyne with skin therapies such as laser treatment or chemical peels may lead to other side effects such as redness, swelling, heat and/or pain of the skin (inflammatory reaction). Tell your doctor if you have had any of these procedures.
- Within the first 24 hours after treatment with Restylane Refyne, you should avoid or minimize hard (strenuous) exercise. You should also minimize exposure to extensive sun or heat, as any of these may cause temporary redness, swelling, and/or itching at the injection site. An ice pack (in a suitable cloth, avoiding any direct contact with the skin) can be applied for relief if needed.
- You have a dental block or use topical lidocaine at the same time as the filler treatment. High doses of lidocaine could cause a toxic reaction.
- If you have any additional questions about any topic in this section, please discuss further with your doctor.
Troubleshooting
When should I call my doctor?
You should call your doctor if you have any of the following side effects that last for more than 14 days:
- Bruising
- Swelling
- Pain
- Tenderness
- Redness
- Itching
These side effects typically go away within two weeks.
If you experience fever, redness that spreads to areas around the injection site, drainage, or increasing tenderness or pain that does not go away, you may be at risk for developing an infection. You should call your doctor so that you can be treated with antibiotics.
If you develop blisters or recurring skin sores, this may be cold sores. You should call your doctor so that you can be treated.
If you experience any of the following symptoms, you should call your doctor immediately:
- Unusual pain
- Vision changes
- A white appearance in the skin near the injection site
Any sign of a stroke, including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure (http://www.nlm.nih.gov/medlineplus/stroke.html).
Administration
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Post Marketing Surveillance
What side effects have been voluntarily reported following use of Restylane Refyne with and without lidocaine in and outside of the United States?
The most common reported side effects included reports of temporary swelling (edema) with immediate onset or delayed onset, up to several weeks after treatment. The following events were also reported in decreasing order of frequency:
- lumps or bumps (mass) /hardening (induration)
- skin redness (erythema)
- pain/tenderness
- small bumps (papules/nodules)
- bruising (hematoma)
- short duration of effect
- skin discoloration/darkening skin tone (hyperpigmentation)
- restricted blood flow (ischemia/necrosis) including white skin (pallor)
- presumptive bacterial infection/pockets of pus (abscess formation)
- injection site reactions including burning sensation, discomfort, dryness, exfoliation, irritation and
warmth - allergic reaction (hypersensitivity) /rapid swelling (angioedema)
- inflammation
- implanted gel moving from site of injection (device displacement)
- itching (pruritus)
- uneven appearance of the skin (deformity/overcorrection)
- reduced sense of touch (hypoesthesia), tingling sensation (paraesthesia)
- eye disorders such as eye swelling, blurred vision, ocular discomfort, and visual disturbance
- small area of inflammation in tissue (granuloma/foreign body reaction)
- blisters/vesicles
- rash
- scarring
- acne
- hives (urticaria)
- leakage from implant site (discharge)
- symptoms of reactivation of herpes infection
- skin inflammation (dermatitis)
- muscle disorders such as muscle twitching and muscle spasm
- dilated small blood vessels (telangiectasia)
- non dermatological events including chills, dizziness and shortness of breath (dyspnoea) and headache
- other dermatological events including dry skin, chapped lips and blistering skin (epidermolysis)
When required, treatments for these events included ice, massage, warm compress, local drugs that widen blood vessels, drugs to reduce inflammation (corticosteroids), antibiotics, drugs to relieve
allergy symptoms (antihistamines), drugs to relieve pain (analgesics), medicine to relieve the body of excess fluid (diuretic agents), surgical procedure (incision, drainage or excision), surgery or an enzyme used to help break down hyaluronic acid (hyaluronidase).
Reports of serious adverse events for Restylane Refyne with and without lidocaine are rare. The most commonly reported serious adverse events were injury due to restricted blood flow (ischemia/necrosis), eye disorders, infection/pocket of pus (abscess) and allergic reaction (hypersensitivity). Other concurrent serious adverse events included swelling, bruising/bleeding, skin
discoloration, skin redness (erythema) and pain/tenderness. Serious infection/pocket of pus (abscess) were mostly reported with a time to onset ranging from one day up to 4 months following the injection. Most of the patients were recovering at the time of last
contact. The treatments may include antibiotics, drugs to relieve pain (analgesics), drugs to reduce inflammation (corticosteroids) and an enzyme used to help break down hyaluronic acid (hyaluronidase).
The onset of serious allergic reactions (hypersensitivity) generally vary from immediately to a few weeks post injection. Most of the events were recovering or recovered at the time of last contact. The treatments may include drugs to relieve pain (analgesics), drugs to relieve allergy symptoms (antihistamine), antibiotics, and drugs to reduce inflammation (corticosteroids). Blockage of a blood vessel (vascular occlusion) resulting in restricted blood flow (ischemia/necrosis) and vision changes, have been reported following facial aesthetic treatments with injectable soft tissue fillers with a time to onset ranging from immediate to a few weeks following injection. Blockage of a blood vessel may occur due to an accidental injection into the blood vessel or as a result of local compression of the vessel (embolization), this may rarely affect other organs and rare cases of restriction in blood supply to tissues (ischemic events) after affecting the eye and brain have led to vision loss and stroke (cerebral infarction), respectively. Treatments may include medicine to prevent blood clotting (anticoagulant), medicine to treat allergic reactions (epinephrine), aspirin, an enzyme used to help breakdown hyaluronic acid (hyaluronidase), drugs to reduce inflammation (corticosteroids), drugs to relieve pain (analgesics), local drugs that widen blood vessels (vasodilating agents) including nitropaste, antibiotics, surgery (including drainage), and hyperbaric oxygen.
Delayed‐onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed‐onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures.
Typically, the reported inflammation was responsive to treatment
or resolved on its own.
Post-treatment Checklist
What should I expect following the procedure?
In the clinical study the most common side effects were temporary reactions at the treatment site such as tenderness, swelling, firmness, and lumps/bumps.
These side effects generally lasted 1 to 2 weeks.
See Section 8 for additional information on side effects seen in the clinical study.
Your doctor will also tell you what to expect following treatment. For the first 24 hours, you should avoid or minimize hard (strenuous) exercise. You should also avoid or minimize exposure to extensive sun or heat. Exposure to any of these may cause the area where you were treated to temporarily become red, swell and/or itch. If you experience any of these, an ice pack can be applied for relief.
User Assistance Information
If you believe that you have experienced a serious problem related to Restylane Refyne you should call your doctor. Your questions about Restylane Refyne can be personally answered by contacting the Galderma Laboratories L.P. toll‐free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday to through Friday.
1‐855‐425‐8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised: June 2023
Restylane Defyne
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane® Defyne is a sterile, biodegradable, viscoelastic, non-pyrogenic, clear, colorless and homogeneous soft hyaluronic acid gel. Restylane ® Defyne is crosslinked with BDDE (1.4- butanediol diglycidylether). The product has a sodium hyaluronate concentration of 20 mg/mL in phosphate buffered saline at pH 7 and contains 3 mg/mL lidocaine hydrochloride.
Indication
Restylane® Defyne is indicated for injection into the mid-to-deep dermis for correction of moderate to severe, deep facial wrinkles and folds (such as nasolabial folds) in patients over the age of 21. Restylane® Defyne is indicated for injection into the mid-to deep dermis (subcutaneous and/or supraperiosteal) for augmentation of the chin region to improve the chin profile in patients with mild to moderate chin retrusion over the age of 21.
How Supplied
Restylane® Defyne injectable gel is supplied in individual treatment syringes with needles as indicated on the carton. The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile. Do not resterilize. Do not use if package is open or damaged.
Self Life and Storage
Restylane® Defyne must be used prior to the expiration date on the package. Store at a temperature of up to 25ºC/77ºF. Do not freeze. Protect from sunlight. Refrigeration is not
required.
Restylane® Defyne injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Galderma Laboratories, L.P. immediately at 1-855-425-8722
Do not use if the package is damaged or if expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
To place an order, contact. Galderma Laboratories, L.P. at 1-855-425-8722
Contraindications
- Restylane® Defyne is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane® Defyne may contain trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- Restylane® Defyne contains lidocaine and is contraindicated for patients with a history of allergies to such material or other amide type local anesthetics.
Warnings
- Defer use of Restylane® Defyne at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the underlying process has been controlled.
- Restylane® Defyne must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Introduction of Restylane® Defyne into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist shoul an intravascular injection occur (see Health Care Professional Instructions).
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules should be considered and treated as a soft tissue infection. For additional information please see Adverse Events section.
For additional information, please see the Post-Marketing Surveillance in Adverse Events.
Precautions
- Restylane® Defyne is packaged for single-patient and single-session use only. Do not resterilize. Do not use if package is open or damaged.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience and knowledge about the anatomy at and around the site of injection in order to minimize the risks of potential complications (perforation or compression of vessels, nerves and other vulnerable structures).
- The safety and effectiveness other than for the treatment of chin and nasolabial folds have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- Restylane® Defyne is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- Restylane® Defyne should not be mixed with other products before implantation of the device.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 22 years has not been established.
- Injection of Restylane® Defyne in patients with pre-existing tendency toward edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up. Page 3 of 27
- Injection of Restylane® Defyne too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable lumps.
- Restylane® Defyne should be used with caution in patients on immunosuppressive therapy.
- This product should be used with caution in patients with a tendency to form hypertrophic scars or any other healing disorders.
- Restylane® Defyne should be used with caution in patients with bleeding disorders.
- Avoid injecting the product into areas in close proximity to a permanent implant, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane® Defyne into an area where an implant other than hyaluronic acid has been placed.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and anticoagulants) may, as with any injection, experience increased bruising or bleeding at treatment sites.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures at least until any initial swelling and redness has resolved.
- If epilation, UV radiation or laser treatment, mechanical or chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane® Defyne, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane® Defyne is administered before the skin has healed completely after such a procedure.
- Injections of Restylane® Defyne into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Post inflammatory pigmentation changes may occur after dermal filler injections in people with dark skin (Fitzpatrick Type IV-VI). Keloid formation was not observed in studies involving 421 patients whereof 49 patients with Fitzpatrick Type V-VI.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- Individual variation and treatment area may affect the bio-degradation of Restylane® Defyne, and product might be detected in the tissue even after the clinical effect has disappeared.
- Restylane® Defyne injectable gel is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Galderma Laboratories, L.P. at 1-855-425-8722.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer lock and needle hub connection.
- Based on clinical studies, the maximum recommended injected volume per patient and treatment for the treatment of moderate to severe nasolabial folds is 4 mL. For augmentation of the chin region to improve the chin profile, the maximum recommended injected volume per patient and treatment is also 4 mL (i.e., 2 mL in the chin and 2 mL in the area inferior to the lower lip, between the two lines from oral commissures up to the pre-jowl sulcus). The safety of injecting greater amounts has not been established.
- Considerations should be given to the total dose of lidocaine administered if dental block or topical administration of lidocaine is used concurrently. High doses of lidocaine (more than 400 mg) can cause acute toxic reactions manifesting as symptoms affecting the central nervous system and cardiac conduction.
- Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type anesthetics, e.g. certain anti-arrhythmics, since the systemic toxic effects can be additive.
- Lidocaine should be used cautiously in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction.
Adverse Experiences
A. Clinical Evaluation of Restylane® Defyne
Pivotal Study for Restylane® Defyne in correction of moderate to severe, deep facial wrinkles and folds (such as nasolabial folds) One hundred sixty two (162) subjects were enrolled in a randomized, double-blinded (subject and evaluator), active controlled, split-face comparison clinical trial to evaluate the safety and effectiveness of Restylane® Defyne vs. a non-lidocaine-containing comparator. Touch-up treatments occurred approximately 3 weeks after initial injection, as needed to achieve volume correction. After 48 weeks, subjects could opt for retreatment with Restylane® Defyne to both sides of the face, with a subsequent touch-up as needed 3 weeks afterwards. One hundred twenty four subjects (124, 76.5%) opted for retreatment.
Pre-printed diary forms were used by subjects for subject-reported assessments of specific signs and symptoms experienced during each of the first 21 days after initial, touch-up, and repeat treatments. Subjects rated each treatment site response as “Mild”, “Moderate”, “Severe” or “None.” Of the 162 subjects who received treatment, 98.8 (160 subjects) completed the diary forms. Of the 124 subjects who opted for retreatment, 100% of subjects completed the diary
forms after retreatment.
After initial treatment, subjects rated pre-defined treatment site responses (redness, swelling, bruising, lump/bump formation, pain/tenderness, and itching) as predominantly mild or moderate in severity (Table 1), typically with a duration of 1 to 2 weeks (Table 2). Based on data from 124 subjects, no increase in frequency or in severity of signs/symptoms was observed following the retreatment injection or retreatment touch-up injection. The trend in adverse events remained the same across subject skin types. Among the 73 subjects of Fitzpatrick Skin Types IV, V, and VI (27 of which were of Skin Type V or VI) in the study, no cases of keloid formation or of hyperpigmentation were reported. Treatment site responses reported in subject diaries that lasted longer than 3 weeks were considered adverse events (AEs). AEs were also reported by the Treating Investigator at all follow-up visits where applicable. Among the 162 treated subjects, 11.7% (19/162) experienced device- and injection-related AEs following initial and touch-up treatment, as well as retreatment and touch-up treatment. These subjects reported a total of 19 events related to control treatment and 20 events related to Restylane® Defyne. The most common of treatment site responses was injection site swelling, which was reported for 5 subjects. Injection site erythema and injection site pain were reported for 4 and 2 subjects, respectively.
Other treatment site responses (inflammation, hematoma, discomfort, and mass) were reported for 1 subject each. Other related adverse events included skin tightness, dermatitis allergic, interstitial granulomatous dermatitis, salivary hypersecretion, sensitivity of teeth, presyncope, and arterial stenosis which were all reported for 1 subject each. Seven subjects reported 8 serious adverse events (SAEs) that were considered to be unrelated to the device. The events were metastatic lung cancer, colon cancer, small bowel obstruction with uterine fibroid tumors, benign cyst on the right ovary, herpes zoster (shingles), febrile diarrhea, and lumbar spinal stenosis resulting in a spinal fusion.
Treatment site responses after initial treatments are summarized by severity in Table 1 and by duration in Table 2.
Table 1 - Treatment Site Responses by Maximum Severity Occurring In Subjects After
Initial Treatment
Restylane® Defyne (N=162)
n (%)
Control (N=162)
n (%)
Mild Moderate Severe Total Mild Moderate Severe Total
Post-Initial Injectiona
(N= 160 for Restylane® Defyne and N= 160 for the control)
Redness 66 (41.3) 27 (16.9) 8 (5.0) 101 (63.1) 65 (40.6) 27 (16.9) 9 (5.6) 101 (63.1)
Swelling 60 (37.5) 45 (28.1) 14 (8.8) 119 (74.4) 61 (38.1) 42 (26.3) 15 (9.4) 118 (73.8)
Bruising 48 (30.0) 36 (22.5) 11 (6.9) 95 (59.4) 47 (29.4) 37 (23.1) 13 (8.1) 97 (60.6)
Lump/Bump
Formation 51 (31.9) 39 (24.4) 15 (9.4) 105 (65.6) 43 (26.9) 37 (23.1) 14 (8.8) 94 (58.8)
Pain/Tenderness 64 (40.0) 28 (17.5) 8 (5.0) 100 (62.5) 60 (37.5) 23 (14.4) 11 (6.9) 94 (58.8)
Itching 28 (17.5) 9 (5.6) 3 (1.9) 40 (25.0) 24 (15.0) 8 (5.0) 1 (0.6) 33 (20.6)
Percentages are based on total number of subjects who reported local tolerability assessments in a subject diary.
a Number of subjects who completed subject diaries.
Page 6 of 27
Table 2 - Duration of Treatment Site Responses Occurring In Subjects After Initial
Treatment
Injection site
response
Restylane® Defyne (N=162)
n (%)
Control (N=162)
n (%)
Durationa 1-3 Days 4-7 Days
8-14
Days
>14
Days
1-3 Days 4-7 Days 8-14 Days >14 Days
Post-Initial Injectionb
(N= 160 for Restylane® Defyne and N= 160 for the control)
Redness 74 (46.3) 19 (11.9) 6 (3.8) 2 (1.3) 72 (45.0) 22 (13.8) 6 (3.8) 1 (0.6)
Swelling 61 (38.1) 31 (19.4) 22 (13.8) 5 (3.1) 57 (35.6) 32 (20.0) 20 (12.5) 9 (5.6)
Brusing 25 (15.6) 42 (26.3) 23 (14.4) 5 (3.1) 29 (18.1) 32 (20.0) 35 (21.9) 1 (0.6)
Lump/bump
Formation 34 (21.3) 35 (21.9) 12 (7.5) 24 (15.0) 40 (25.0) 15 (9.4) 15 (9.4) 24 (15.0)
Pain/tenderness 63 (39.4) 26 (16.3) 7 (4.4) 4 (2.5) 58 (36.3) 22 (13.8) 11 (6.9) 3 (1.9)
Itching 29 (18.1) 8 (5.0) 2 (1.3) 1 (0.6) 24 (15.0) 7 (4.4) 2 (1.3) 0
Percentages are based on total number of subjects who reported local tolerability assessments in a subject diary.
a Number of days was defined as the sum of days when a sign/symptom was scored 'Mild' or higher.
b Number of subjects who completed subject diaries.
Pivotal Study for Restylane® Defyne for augmentation of the chin region to improve the chin
profile One hundred forty (140) subjects were enrolled in a randomized, no-treatment-controlled, evaluator-blinded, multicenter study to evaluate the effectiveness and safety of Restylane® Defyne for the augmentation of the chin region to improve the chin profile. A touch-up treatment was offered after 4 weeks if optimal correction was not achieved at the initial treatment. Out of the 107 subjects randomized to treatment, 78 had the touch-up done at Week 4. At week 48, subjects in the no-treatment control group were offered an optional treatment and subjects in the treatment group were offered an optional additional treatment, 58 subjects in the treatment group and 23 subjects in the no-treatment control group opted for the offered treatment.
The key safety outcomes for this study are presented below in Tables 3 - 8. Subject reported
injection related events are presented in Table 3 – Table 7. Adverse events (AEs) are presented in
Table 8.
Clinical Trials
https://pubmed.ncbi.nlm.nih.gov/?term=restylane+define&filter=pubt.clinicaltrial&page=1
Directions For Assembly
-
Assembly Of Needle To Syringe
Use surgical gloves, remove the cap from the needle and the tip cap from the syringe. Hold firmly around the syringe barrel and grasp the needle shield with the other hand. Screw the needle tight onto the syringe by simultaneously pushing and rotating firmly until the needle is completely locked. To ensure proper assembly, minimize the gap between the needle shield and the syringe. See the figure below.
Remove the needle shield just before injection by pulling it straight out. Do not rotate.
Note: Improper assembly may cause leakage or needle disconnection.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications,warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
Treatment Procedures
-
Injection Technique
1. Restylane® Defyne is a cross-linked formulation resulting in a robust injectable gel that can be injected using a 27 G needle, for volumizing and contouring of facial wrinkles and folds.
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction Pre-treatment photographs are recommended. 3. Although the study showed that lidocaine in Restylane® Defyne had an effect on pain supplementary anesthesia may be used for additional pain management during and after injection.
4. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic.
5. To avoid breakage of the needle, do not attempt to bend or otherwise manipulate it before or during treatment. If needle gets bent, discard it and complete the procedure with a replacement needle. Do not re-shield used needles. Recapping by hand is a hazardous practice and should be avoided. Discard unshielded needles in approved sharps collectors.
6. Before injection press the plunger rod carefully until a small droplet is visible at the tip of
the needle.
7. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not in a blood vessel.
8. Inject Restylane® Defyne slowly by applying even pressure on the plunger rod with the thumb or palm of the hand. Do not apply excessive pressure to the syringe at any time. If resistance is encountered the needle should be partially withdrawn and repositioned or full withdrawn and checked for function and replaced if needed.
9. After the first small amount of material has been injected into the patient, wait a few seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
10. The injection technique and the depth of injection administered may vary based on the subject’s treatment needs.
a. Correction of moderate to severe, deep nasolabial folds A retrograde linear threading technique, serial puncture injections, or a combination of the 2 have been used to achieve optimal results. Injections should be done into the mid-to-deep dermis. Injecting the product too superficially may result in visible lumps and/or bluish discoloration.
b. Augmentation of chin region to improve chin profile A linear antegrade and retrograde threading technique, serial puncture injections, fern pattern technique and fanning technique have been used to achieve optimal results. The product should be injected into the mid-to-deep dermis or in subcutaneous to supraperiosteal implantation.
11. It is important that the injection be stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin. It is recommended to change needle for each new treatment site.
12. Injection volume to achieve optimal correction may vary based on the subject’s treatment needs.
a. Correction of moderate to severe, deep nasolabial folds The injection volume for the initial injection is generally about 1.4 mL per treatment site (NLF). Injection volume to achieve optimal correction (touch-up) and re-treatment is generally about 0.7 mL per treatment site. The maximum volume studied is 2 mL per NLF and treatment occasion.
b. Augmentation of chin region to improve chin profile. The initial injection volume is generally about 2.6 mL depending on severity of chin retrusion. Injection volume to achieve optimal correction (touch-up) is generally about 1.4 mL. The injection volume for re-treatment is generally 2.1 mL. Recommended maximum injected volume per patient for the initial and retreatment injections is 4 mL for chin (2 mL in the chin and 2 mL in the area inferior to the lower lip, between the two lines from oral commissures up to the pre-jowl sulcus). For touch-up injections, the maximum volume studied is 2 mL.
13. Correct to 100% of the desired volume effect. Do not overcorrect.
14. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
15. When injection is completed, the treated site may be gently massaged to mold the product to the contour of the surrounding tissue and assure that it is evenly distributed. If overcorrection occurs, massage the area between your fingers or against an underlying superficial bone to obtain optimal results.
16. With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of treatment. In these cases, it is better to invite the patient back to the office for a touch-up treatment.
17. Patients may experience treatment site responses, which typically resolve within 1 to 2 weeks. An ice pack may be applied for a short period following treatment to minimize swelling and reduce pain. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
18. The health care practitioner should instruct the patient to promptly report any problems associated with the use of Restylane® Defyne.
Sterile Needles
-
PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane® Defyne?
Restylane® Defyne is a dermal filler injected under the (facial) skin. Once in place, it helps smooth away your “laugh lines” – the wrinkles and folds that may form at the sides of your nose and run down toward the corners of your mouth. Restylane® Defyne may also be used to improve the profile, shape and size of your chin.
Restylane® Defyne is made out of hyaluronic acid ‐ a naturally occurring sugar, found in the body that gives the skin moisture, volume and elasticity – and a small amount of lidocaine, which is a commonly used local anesthetic to numb the skin.
The hyaluronic acid is crosslinked with BDDE, an ingredient that helps form a network of hyaluronic acid to provide a gel filler that lasts longer. Hyaluronic acid fillers, including Restylane® Defyne, contains hyaluronic acid that has been modified to last longer in the body than the naturally occurring hyaluronic acid.
What is Restylane® Defyne for?
As you age, your facial skin begins to lose its elasticity and volume. As a result, your “laugh lines”, the creases that run from the sides of your nose toward the corners of your mouth, become more pronounced. Restylane® Defyne injectable gel is designed to temporarily help counter this by smoothing out these wrinkles and folds and restoring a natural, soft look to your face.
Restylane® Defyne may also be used for augmentation of the chin region to improve the chin profile in patients with mild to moderate chin retrusion over the age of 21. This means it may be used in the chin area to improve the profile, shape and size of your chin. Restylane® Defyne has been shown to maintain this effect for up to 12 months.
Note: Facial features can differ. Speak to your doctor about the lines on your face that are appropriate for treatment with Restylane® Defyne.
How is Restylane® Defyne used?
Restylane® Defyne is injected into the facial skin through a small needle to smooth facial wrinkles and folds (laugh lines), resulting in a more youthful appearance of the skin. Restylane® Defyne may also be injected in your chin improve the profile, shape and size of your chin. For most patients, the procedure only takes 15 – 30 minutes.
Are there any reasons why I should not receive Restylane® Defyne? Before using Restylane® Defyne, your doctor will talk to you about your medical history, to determine if you are an appropriate candidate for treatment. You will be asked questions about possible allergies to ensure that Restylane® Defyne can be safely administered. Tell your doctor about all your medical conditions, including if you:
- Have severe allergies with a history of severe reactions (anaphylaxis). Use of Restylane® Defyne may result in an allergic reaction.
- Are allergic to the anesthetic lidocaine or to any of the proteins used to make the hyaluronic acid in Restylane® Defyne (bacterial proteins). Use may result in an allergic reaction. If you are not sure about your medical history concerning these allergies, please discuss further with your doctor.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
- Restylane® Defyne helps improve the profile and appearance of your chin and helps treat laugh lines – the natural facial wrinkles and folds that can occur due to aging. Restylane® Defyne has not been tested to treat any other types of wrinkles.
- Restylane® Defyne may be unintentionally injected into a blood vessel during the procedure. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your doctor immediately.
- The use of Restylane® Defyne if you have skin sores, pimples, rashes, hives, cysts, or infections should be postponed until healing is complete. Use of Restylane® Defyne in these instances could delay healing or make your skin problems worse.
- Any time a dermal filler gel like Restylane® Defyne is injected into facial skin there is risk of infection, which could appear as small, swollen or red bumps. These are called inflammatory papules. These infections are rare, however you should talk to your doctor about further treatment if you see any of these signs or symptoms.
- Restylane® Defyne is for adults over the ages of 21.
- Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. The safety of Restylane® Defyne has not been studied in women who are pregnant or breastfeeding. The risk of using Restylane® Defyne in pregnant or breastfeeding women is unknown.
- Tell your doctor about any medication you are taking. You may have a greater risk of developing an infection if you use Restylane® Defyne while taking any medication that reduces your body’s natural defense system. These medications are called “immunosuppressants” because they stop your body’s immune system from functioning normally.
- Tell your doctor about any medication you are taking. Some medication like aspirin and warfarin can thin your blood, which may increase your risk of bleeding or prolong any bleeding that occurs. These medications also increase your risk of bruising or bleeding at the injection site.
- As with any injection procedure, you may have a higher risk of bruising or bleeding at the injection site if you have a bleeding disorder.
- If you have any history of scarring, particularly thick and stiff scars, or any skin color (pigmentation) disorders, talk to your doctor about this before your procedure. Scarring and skin color changes can occur with hyaluronic acid fillers in general. When Restylane® Defyne was studied in patients with different skin tones (pale to dark), there were no reports by patients of excessive scarring (keloids) or changes in skin color.
- The use of Restylane® Defyne with skin therapies such as laser treatment, mechanical or chemical peels or hair removal may lead to other side effects such as redness, swelling, heat and/or pain of the skin (inflammatory reaction). Tell your doctor if you have had any of these procedures.
- If you have had cold sores in the past, there is a risk that they will return after your procedure with Restylane® Defyne.
- Within the first 24 hours after treatment with Restylane® Defyne, you should avoid or minimize hard (strenuous) exercise. You should also minimize exposure to extensive sun, UV lamps, indoor tanning beds/booths, or extreme heat and cold as any of these may cause temporary redness, swelling, and/or itching at the injection site. Exposure to UV sources may result in irritation at the site of treatment. An ice pack can be applied for relief, if needed. If you have any additional questions about any topic in this section, please discuss further with your doctor.
Troubleshooting
When should I call my doctor?
If you experience any of the following symptoms, you should call your doctor immediately:
- Unusual pain
- Vision changes
- A white appearance in the skin near the injection site
- Any sign of a stroke, including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure (http://www.nlm.nih.gov/medlineplus/stroke.html)
You should call your doctor if you have any of the following side effects that last for more than 14 days:
- Bruising
- Swelling
- Pain
- Tenderness
- Redness
- Itching
These side effects typically go away within two weeks. If you experience fever, redness that spreads to areas around the injection site, drainage, or increasing tenderness or pain that does not go away, you may be at risk for developing an infection. You should call your doctor so that you can be treated with antibiotics. If you develop blisters or recurring skin sores, this may be cold sores. You should call your doctor so that you can be treated.
Be sure to call your doctor if you have:
- Significant pain away from the injection site
- Any side effect that occurs weeks or months after treatment
- Any other symptoms that cause you concern.
Administration
-
Post Marketing Surveillance
In the study of Restylane® Defyne for correction of wrinkles and folds that form around your nose and
extend down to the corners of your mouth (laugh lines), most patients reported the following side effects at the site where they received the injection:
- Swelling
- Lumps/Bump Formation
- Redness
- Pain/Tenderness
- Bruising
- Itching
Most patients said their side effects were mild, short‐lived and did not require them to call their doctor. These patients said that their side effects disappeared within 1‐2 weeks.
Patients also reported that the anesthetic lidocaine, which is part of the Restylane® Defyne injection and used to numb the injection site, significantly reduced pain during and after their procedure.
Post-treatment Checklist
- What should I expect following the procedure?
Your doctor will also tell you what to expect following treatment.
A clean cloth dipped in cold water (cold compresses) wrung out, and applied to the injected area may be used immediately after treatment to reduce swelling. - Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- Avoid taking aspirin, NSAID, St. John’s Wort, blood thinners, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site.
- Minimize strenuous exercise and exposure to excessive heat, sun, or UV lamps for the first 24 hours after treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site. Until there is no redness or swelling, avoid exposure of the treated area to intense cold or heat such as sun lamps or sun bathing. In the clinical studies the most common side effects were temporary reactions at the treatment site such as pain, tenderness, swelling, bruising, redness, itching, and lumps/bumps. These side effects generally lasted 1 to 2 weeks. See Section 8 for additional information on side effects seen in the clinical studies.
User Assistance Information
Manufactured for
Galderma Laboratories, L.P.
14501 North Freeway
Fort Worth, TX 76177
U.S.A
Phone: 1-855-425-8722
Manufactured by:
Q-Med AB
Seminariegatan 21
SE-752 28 Uppsala
Sweden
Restylane® and Galderma are registered trademarks.
All other trademarks are the property of their respective owners.
Revised: June 2023
Part Number: 90-99330-02
Restylane Kysse
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane® Kysse is a sterile, biodegradable, viscoelastic, non-pyrogenic, clear, colorless, flexible and homogeneous gel composed of hyaluronic acid of bacterial origin, with a moderate lifting capacity. Restylane® Kysse is crosslinked with BDDE (1,4-butanediol diglycidylether). The product has a sodium hyaluronate concentration of 20 mg/mL in phosphate buffered saline at pH 7 and contains 3 mg/mL lidocaine hydrochloride.
Indication
Restylane® Kysse is indicated for injection into the lips for lip augmentation and the correction of upper perioral rhytids in patients over the age of 21.
How Supplied
Restylane® Kysse is supplied in individual treatment syringes with needles as indicated on the carton. The volume in each syringe is as stated on the syringe label and on the carton. The content of the syringe is sterile. Do not resterilize. Do not use the product if package is open or damaged or if expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
Self Life and Storage
Restylane® Kysse must be used prior to the expiration date on the package. Store at a temperature of up to 25ºC/77ºF. Do not freeze. Protect from sunlight. Refrigeration is not required.
Restylane® Kysse injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Galderma Laboratories, L.P. immediately at 1-855- 425-8722.
To place an order, contact Galderma Laboratories, L.P. at 1-855-425-8722
Contraindications
- Restylane® Kysse is contraindicated for patients with severe allergies such as manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane® Kysse may contain trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- Restylane® Kysse contains lidocaine and is contraindicated for patients with a history of allergies to such material or other amide type anesthetics.
Warnings
- Introduction of Restylane® Kysse into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see Health Care Professional Instructions).
- Defer use of Restylane® Kysse at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection or tumors, in or near the treatment site is present until the process has been controlled.
- Restylane® Kysse must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules should be considered and treated as a soft tissue infection.
- For additional information please see the Post-Marketing Surveillance in Adverse Events section.
Precautions
- Restylane® Kysse is packaged for single-patient and single-session use only. Do not resterilize. Do not use if package is open or damaged.
- Restylane® Kysse is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- In order to minimize the risks of potential complications, this product should only be used by health care professionals who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- The recommended maximum injected volume per subject and treatment is 6 mL (i.e., 3 mL for lips and 3 mL for perioral area).
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- Avoid injecting Restylane® Kysse into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane® Kysse into an area where an implant other than hyaluronic acid has been placed.
- Inflammatory pigmentation changes and scarring may occur following dermal filler injections. Patients with abnormal wound healing or dark skin (Fitzpatrick Type IV-VI) may be more prone to develop hypertrophic scarring and keloid formation.
- Injections of Restylane® Kysse into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Restylane® Kysse should be used with caution in patients on immunosuppressive therapy.
- Restylane® Kysse should be used with caution in patients with bleeding disorders.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at treatment sites.
- The safety of Restylane® Kysse with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials. If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane® Kysse, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane® Kysse is administered before the skin has healed completely after such a procedure.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
- The safety of Restylane® Kysse for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
- Individual variation and treatment area may affect the bio-degradation of Restylane® Kysse, product remnants may remain in the tissue even when the clinical effect has returned to baseline.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer lock and needle hub connection.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- Restylane ®Kysse injectable gel is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe.
- Restylane® Kysse should not be mixed with other products before implantation of the device.
- Restylane Kysse contains lidocaine. If additional dental block or topical lidocaine or other local anesthetics or agents structurally related to amide-type local anesthetics are used concurrently with the product the following considerations should be observed:
o Use with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction.
o High doses of lidocaine (more than 4.5 mg/kg of bodyweight) can cause acute toxic reactions manifesting as symptoms affecting the central nervous system and cardiac conduction o Systemic toxic effects could be additive.
Adverse Experiences
A. US Pivotal Study of Restylane® Kysse In the randomized, controlled, evaluator-blinded, multi-center clinical trial to evaluate the safety and effectiveness of Restylane® Kysse versus control for lip augmentation and correction of perioral rhytids, in total 273 subjects were randomized and treated in a 2:1 ratio with either Restylane® Kysse or control.
Preprinted diary forms were completed by subjects to record specific signs and symptoms experienced during the 30 days after initial treatment, touch-up treatment (if performed), and retreatment (if performed). Subjects rated each injection site reactions (ISR) as None, Tolerable, Affects Daily Activities, or Disabling. The intensity and duration of ISRs reported by > 5% of subjects who completed the diary following initial treatment are summarized in Table 1 and Table 2, respectively.
Table 3 shows the intensity
and duration of ISR after retreatment reported by > 5% of subjects. The majority of ISRs were tolerable in intensity, and lasted less than 2 weeks. There were no significant differences in the ISRs reported in the Restylane® Kysse treatment group compared to the control group. ISRs in both groups were typically reported at a lower incident rate and intensity, and shorter duration following touch-up compared to initial treatment.
Adverse events (AEs) were evaluated by Investigators throughout entirety of the study. After initial and touch up treatment, treatment-related treatment-emergent AEs were reported in 21.1% (39/185) of subjects treated with Restylane® Kysse and 25.0% (22/88) of subjects treated with control. Regardless of treatment group, most related TEAEs were mild in severity and required no action. There were no treatment-related serious adverse events reported.
The severity and duration of TEAEs occurring in > 5% of subjects in either treatment group are summarized in Table 4 and Table 5. Common related TEAEs included injection site mass, bruising, and nodules. Related events of injection site mass or nodules typically lasted less than 30 days, and injection site bruising lasted less than 14 days. Treatment-related AEs occurring in ≤ 5% of subject after initial and touch-up treatment included injection site swelling, injection site pain, oral herpes, injection site hypersensitivity, injection site hypertrophy, angioedema, herpes simplex, injection site discharge, dryness, hemorrhage, induration, edema, papule, and vesicles.
Directions For Assembly
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Assembly Of Needle To Syringe
Use surgical gloves, remove the cap from the needle and the tip cap from the syringe. Hold firmly around the syringe barrel and grasp the needle shield with the other hand. Screw the needle tight onto the syringe by simultaneously pushing and rotating firmly until the needle is completely locked. To ensure proper assembly, minimize the gap between the needle shield and the syringe. See the figure below.
Remove the needle shield just before injection by pulling it straight out. Do not rotate.
Note: Improper assembly may cause leakage or needle disconnection.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications,warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
Treatment Procedures
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Injection Technique
2. Restylane® Kysse contains lidocaine hydrochloride, but additional local anesthesia/nerve block may be used to further reduce pain on injection.
3. Aseptic technique and standard practice to prevent cross infections should be observed at all times including the use of disposable gloves during the injection procedure. All traces of makeup below the level of the lower orbital rim should be removed prior to any injection. The treatment site should be cleaned with a suitable antiseptic solution.
4. To avoid breakage of the needle, do not attempt to bend or otherwise manipulate it before or during treatment. If needle gets bent, discard it and complete the procedure with a replacement needle. Do not re-shield used needles. Recapping by hand is a hazardous practice and should be avoided. Discard unshielded needles in approved sharps collectors.
5. Before injection, press the plunger rod carefully until a small droplet is visible at the tip of the needle and the plunger is at the 1 mL graduation mark.
6. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not in a blood vessel.
7. Inject slowly by gently pressing down on the plunger rod with the thumb or palm of the hand applying even pressure on the plunger rod. Do not apply excessive pressure to the syringe at
any time. If the needle is blocked, do not increase the pressure on the plunger rod. Instead,stop the injection and replace the needle. Presence of scar tissue may impede advancement of the needle. If resistance is encountered the needle should be partially withdrawn and repositioned or fully withdrawn and checked for function.
8. The injection technique may vary based on the subject’s treatment needs and the health care professional’s experience and preference. The techniques may include:
- Linear antegrade threading: also called push-ahead technique as some product is pushed ahead of the needle. Once the needle in is in place, the product is injected on withdrawal of the needle.
- Linear retrograde threading: the needle is threaded into the tissue at the appropriate depth, and the product in injected as a straight line on withdrawal of the needle.
- Serial puncture: numerous small needle insertions to deliver a small bleb or bolus of the product, repeated along a line or regions of the tissues.
- Fern pattern: vertical or diagonal linear threads with needle entry from the centre of line or the edge of vermilion border of the lip with the needle pushing into the body or vermilion of the lip and a taper shaped pattern of product injected on withdrawal of the needle. - Fan technique: a number of linear threads to spread the product over a wider area.
- Other: at the choice of the health care professional.
9. For lip augmentation, Restylane® Kysse should be injected into the submucosal layer of the lip. Care should be taken to avoid intramuscular injection. For correction of perioral rhytids and philtral column, Restylane® Kysse should be injected into the mid-dermis to the subcutaneous layer. If Restylane® Kysse is injected too superficially this may result in visible lumps and/or bluish discoloration. It is recommended to change needle for each new treatment site.
10. It is important that the injection is stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
11. It is recommended that the dose should not exceed 1.5 mL per upper lip and 1.5 mL per lower lip per treatment (touch-up included). Optional treatment of perioral rhytids and philtral column may be performed. The recommended maximum injected volume per subject and treatment (touch-up volume included) is 6 mL.
12. Correct to 100% of the desired volume effect. Do not overcorrect.
13. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
14. After each injection, the lip should be observed to assess the degree of enhancement and the uniformity of the implant. The lips should be gently palpated to ensure an even deposition of the implant. Palpated “skip areas” (areas not containing product) should be treated with additional implant material or by gentle massage of the area until a uniform implant is palpable.
15. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection should occur, the area should be firmly massaged between fingers to obtain optimal results. If the treated area is swollen directly after the injection, an ice pack with adequate protective cloth can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
16. Monitor the subject for at least one hour after the procedure in order to detect any immediate adverse events. Patients may have mild to moderate injection site reactions, which typically resolve within a few days.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane Kysse?
Restylane Kysse is a clear injectable gel composed of hyaluronic acid (HA).
HA is a naturally occurring sugar, found in the human body. Restylane Kysse is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. HA fillers, including Restylane Kysse, contains HA that has been modified to last longer in the body than the naturally occurring HA. Restylane Kysse contains 0.3 % lidocaine to reduce pain during injection.
What is Restylane Kysse for?
Restylane Kysse is injected into the lips and the lines around the upper lip to temporarily add fullness to the lips and help smooth the wrinkles around the upper lip (perioral lines) in patients over the age of 21.
How is Restylane Kysse used?
Restylane Kysse is injected with an ultrafine needle into your lips to add fullness. It can also be injected into the skin above your lips to help smooth the wrinkles around your upper lip (perioral lines). The picture below shows the treatment areas for Restylane Kysse.
Are there any reasons why I should not receive Restylane Kysse?
Your doctor will ask about your medical history to determine if Restylane Kysse is right for you. Patients with any of these conditions should not use Restylane Kysse:
- Highly allergic (for example: a history of severe allergic reaction or multiple severe allergies). Use may result in an allergic reaction.
- Allergic to gram positive bacteria
- If you have previous experience with allergic reactions to HA fillers. Use may result in an allergic reaction.
- Allergic to anesthetics, such as lidocaine. Use may result in an allergic reaction.
Safety
What precautions should my doctor discuss with me?
- The use of Restylane Kysse where skin sores, pimples, rashes, hives, cysts, or infections are present should be postponed until healing is complete.
Use of Restylane Kysse where these are present could delay healing or make your skin problems worse. - As with any injection procedure, you may have a higher risk of bruising or bleeding at the injection site if you have a bleeding disorder.
- Tell your doctor if you are using St. John’s Wort, high doses of Vitamin E supplements, aspirin, and other NSAIDs, such as ibuprofen, because these may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning other skin therapies such as laser, mechanical or chemical peeling, micro needling and hair removal after treatment. The use of Restylane Kysse with these skin therapies may lead to other side effects such as inflammation.
- After treatment with Restylane Kysse, you should minimize exposure to the sun and avoid being in the heat and cold until any redness or swelling has disappeared. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are pregnant or breastfeeding. The safety and effectiveness of Restylane Kysse has not been established in pregnant women or nursing mothers.
- Tell your doctor if you are on a therapy to decrease the body’s immune response. Treatment may result in an increased risk of infection.
- Tell your doctor if you have a history of thick, hard scars (excessive scarring). The safety and effectiveness of Restylane Kysse in patients with a history of thick, hard scars has not been studied and may result in additional scarring.
- Tell your doctor if you have a dental block or use topical lidocaine at the same time as the filler treatment. High doses of lidocaine could cause a toxic reaction.
Troubleshooting
When should I call my doctor?
You should call your doctor immediately if you have:
- Changes in your vision
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) (http://www.nlm.nih.gov/medlineplus/stroke.html)
- White appearance of the skin
- Unusual pain during or shortly after treatment.
Be sure to call your doctor if you have:
- Persistent injection site reactions beyond 14 days, as most side effects such as bruising, swelling, pain, tenderness, redness, and itching will usually go away within one to two weeks
- Blisters or skin sores that recur, which may signal the presence of a herpes infection
- Any signs of infection such as fever, redness that spreads to surrounding areas, drainage, increasing tenderness or increasing pain that does not go away
- Significant pain away from the injection site
- Any side effect that occurs weeks or months after treatment
- Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
What side effects were seen in the clinical study?
In the study of Restylane Kysse, most side effects were mild or moderate in nature and their duration was short lasting (7 days or less).
The most common side effects included, but was not limited to, temporary injection site responses such as:
o redness,
o pain/tenderness,
o firmness,
o swelling,
o lumps/bumps,
o bruising,
o itching,
o discoloration.
Other potential risks may arise from an injection of a dermal filler gel such as Restylane Kysse including the following:
- Infection ‐ Any time a dermal filler gel like Restylane Kysse is injected into facial skin there is risk of infection, which could appear as small, swollen or red bumps. These are called inflammatory papules. These infections are rare, however you should talk to your doctor about further treatment if you see any of these signs or symptoms.
- Scarring ‐ While it is very rare, scarring may occur with an injection procedure. When Restylane Kysse was studied, there was no excessive scarring (a condition called keloids) observed in patients who received Restylane Kysse.
- Change in skin tone ‐ If you are African American, you may have a higher risk of darkening of the skin tone (hyperpigmentation) in the treated area. This may take several weeks to disappear. When Restylane Kysse was studied, this change in skin tone did not occur in patients who received Restylane Kysse.
- Cold sores ‐ If you have had cold sores in the past, there is a risk that they will return after your procedure with Restylane Kysse.
- Age and pregnancy – Restylane Kysse has not been studied in patients under 22 years of age, patients who are pregnant or patients who are breastfeeding. If you are pregnant, trying to become pregnant, or breastfeeding, the safety and effectiveness of Restylane Kysse has not been proven in patients like yourself.
- Vision changes ‐ Vision abnormalities have rarely been reported after treatment with other dermal filler gel treatments.
- Use of other skin therapies ‐ The safety of Restylane Kysse has not been established in patients who have had other skin therapies, such as laser, mechanical, or chemical peeling, and hair removal. If you use Restylane Kysse with any of these skin therapies you may experience other side effects such as redness, swelling, heat and/or pain of the skin (inflammation).
- Ultraviolet (UV) exposure ‐ You should avoid exposing the area(s) treated with Restylane Kysse to excessive sun, UV lamps or indoor tanning beds/booths, and extreme heat and cold until any redness or swelling has disappeared. Exposure to UV sources may result in irritation at the site of treatment.
- One of the risks of Restylane Kysse is that it may be unintentionally injected into a blood vessel during the procedure. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include:
o vision abnormalities, or blindness
o stroke
o temporary scabs
o permanent scarring of the skin
You should tell your doctor immediately if you experience any of these side effects or if you notice anything unusual at the site of treatment. There are also other potential side effects that can occur with dermal filler gel injections. Although most side effects will resolve with time, some side effects may persist longer than 30 days. Your doctor may choose to treat them with medications, such as antibiotics, steroids, or hyaluronidase (an enzyme that breaks down HA). You should discuss the potential treatment risks and benefits with your doctor.
Delayed‐onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed‐onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
What should patients do after receiving treatment?
- A clean cloth dipped in cold water (cold compresses) wrung out, and applied to the injected area may be used immediately after treatment to reduce swelling.
- Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- Avoid taking aspirin, NSAID, St. John’s Wort, blood thinners, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site.
- Minimize strenuous exercise and exposure to excessive heat, sun, or UV lamps for the first 24 hours after treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site. Until there is no redness or swelling, avoid exposure of the treated area to intense cold or heat such as sun lamps or sunbathing.
User Assistance Information
If you believe that you have experienced a serious problem related to Restylane Kysse you should call your doctor. Your questions about Restylane Kysse can be personally answered by contacting the Galderma Laboratories L.P. toll‐free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday to through Friday.
1‐855‐425‐8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised 03/202
Restylane Contour
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane® Contour is a sterile, biodegradable, viscoelastic, non-pyrogenic, clear, colorless, flexible and homogeneous soft gel composed of hyaluronic acid of bacterial origin, with a high lifting capacity. Restylane Contour is crosslinked with BDDE (1,4-butanediol diglycidylether). The product has a sodium hyaluronate concentration of 20 mg/mL in phosphate buffered saline at pH 7 and contains 3 mg/mL lidocaine hydrochloride.
Indication
Restylane Contour is indicated for use in cheek augmentation and correction of midface contour deficiencies in patients over the age of 21.
How Supplied
Restylane Contour is supplied in individual treatment syringes with needles as indicated on the carton. The volume in each syringe is as stated on the syringe label and on the carton. The content of the syringe is sterile. Do not resterilize. Do not use if package is open or damaged
Self Life and Storage
Restylane Contour must be used prior to the expiration date on the package. Store at a temperature of up to 25ºC/77ºF. Do not freeze. Protect from sunlight. Refrigeration is not required.
Restylane Contour injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Galderma Laboratories, L.P. immediately at 1-855-425-8722.
Do not use if the package is damaged or if expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
To place an order, contact Galderma Laboratories, L.P. at 1-855-425-8722
Contraindications
- Restylane Contour is contraindicated for patients with severe allergies such as manifested by a history of anaphylaxis or history of multiple severe allergies.
- Restylane Contour may contain trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- Restylane Contour contains lidocaine and is contraindicated for patients with a history of allergies to such material or other amide type anesthetics.
Warnings
- Introduction of Restylane Contour into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see Health Care Professional Instructions).
- Restylane Contour must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels. It is thought to result from the injury, obstruction, or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area.
- Defer use of Restylane Contour at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
For additional information please see Post Market Surveillance in Adverse Event section.
Precautions
- Restylane Contour is packaged for single-patient use. Do not resterilize. Do not use if package is open or damaged.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- In order to minimize the risks of potential complications, this product should only be used by health care professionals who have appropriate training, experience and knowledgeable about the anatomy at and around the site of injection in order to minimize the risks of potential complications (perforation or compression of vessels, nerves and other vulnerable structures).
- The recommended maximum injected volume per subject and treatment session is 6 mL.
- The safety and effectiveness of cannula injection of Restylane Contour have only been clinically evaluated in one brand of blunt tip cannulas (TSK STERiGLIDE™) that are 25-27 G and 1.5 or 2 inches in length.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- Restylane Contour is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety of Restylane Contour for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
- Injection of Restylane Contour in patients with pre-existing tendency towards edema formation may be associated with prominent discoloration and excessive swelling due to fluid build-up.
- Injection of Restylane Contour too superficially or in facial areas with limited soft tissue support, thin skin or limited soft tissue cover, may result in contour irregularities and palpable lumps.
- Restylane Contour should be used with caution in patients on immunosuppressive therapy.
- This product should be used with caution in patients with a tendency to form hypertrophic scars or any other healing disorders.
- Restylane Contour should be used with caution in patients with bleeding disorders.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs and anticoagulants) may, as with any injection, experience increased bruising or bleeding at treatment sites.
- Avoid injecting Restylane Contour into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane Contour into an area where a nonpermanent implant other than hyaluronic acid has been placed.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures at least until any initial swelling and redness has resolved.
- The safety of Restylane Contour with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials. If any procedure based on active dermal response is considered after treatment with Restylane Contour, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane Contour is administered before the skin has healed completely after such a procedure.
- Injections of Restylane Contour into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- Post inflammatory pigmentation changes may occur after dermal filler injections in people with dark skin (Fitzpatrick Type IV-VI).
- After use, treatment syringes and needles/cannulas may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- Individual variation and treatment area may affect the bio-degradation of Restylane Contour and product might be detected in the tissue even after the clinical effect has disappeared.
- Restylane Contour injectable gel is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe.
- Restylane Contour should not be mixed with other products before implantation of the device.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer lock and needle hub connection.
- Lidocaine should be used with caution in subjects receiving agents structurally related to amidetype anesthetics, e.g. certain anti-arrhythmics, since the systemic toxic effects can be additive.
- Lidocaine should be used with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction.
Adverse Experiences
A. US Pivotal Study of Restylane Contour Study Design
Subjects were treated between October 18, 2018 and November 25, 2019. The database for this PMA supplement reflects data collected through May 22, 2020 and included 270 subjects at 17 investigational sites in the US.
The pivotal study was a randomized, evaluator-blinded, parallel group-, comparator-controlled, multicenter study to evaluate the safety and effectiveness of treatment with Restylane Contour for cheek augmentation and the correction of midface contour deficiencies, versus an approved label comparator product with similar indications for use (Juvéderm Voluma XC ). There were two treatment groups:
- Group A subjects were randomized to either Restylane Contour or Control (Juvéderm Voluma XC ) in a 2:1 ratio (Restylane Contour:Control), and treated using a needle.
- Group B subjects received Restylane Contour only, using a split face design, wherein one cheek was randomized to receive treatment using a small blunt tip cannula and the other cheek was randomized to receive treatment using the co-packed needle. Sites exclusively enrolled subjects for either Group A (210 subjects) or Group B (60 subjects).
Clinical Inclusion and Exclusion Criteria Enrollment in the clinical study was limited to subjects who met the following key inclusion criteria:
- Males and non-pregnant, non-breastfeeding females, age 22 or older
- Grade of 2 (mild), 3 (moderate) or 4 (severe) on each side of the midface on the Medicis Midface Volume Scale (MMVS) as assessed by the Blinded Evaluator
- Written informed consent Subjects were not permitted to be enrolled in the clinical study if they met any of the following key exclusion criteria:
- Known/previous allergy or hypersensitivity to any injectable HA gel or to gram-positive bacterial proteins
- History of allergy or hypersensitivity to lidocaine or other amide-type anesthetics, or topical anesthetics or nerve blocking agents
- Previous use of any permanent (non-biodegradable) or semi-permanent (e.g., calcium hydroxylapatite or Poly-L-Lactic acid) facial tissue augmentation therapy, lifting threads, permanent implants or autologous fat
- Previous use of any HA based or collagen based biodegradable facial tissue augmentation therapy within 12 months prior to the baseline visit
- Abnormal score for midface function, firmness, symmetry or monofilament/cotton wisp tests
- History of other facial treatment/procedure in the previous 6 months that, in the Treating Investigator ’s opinion, would interfere with the study injections and/or study assessments or would expose the subject to undue risk by study participation.
Follow-up Schedule
In the pivotal study, qualified subjects in Group A were randomized to receive treatment with Restylane Contour or Control, or assigned to Restylane Contour treatment in Group B, for augmentation of the cheeks, on Day 1 of the study. Subjects had scheduled visits at 2 and 4 weeks after treatment at baseline. Optional touch-up
treatment was offered at Week 4 if optional correction was not achieved. If a touch-up was performed, a second 2-week and 4-week follow-up visit was scheduled. Subjects had in-clinic follow up visits to evaluate safety and effectiveness at 2, 4, 12, 24, 36, and 48 weeks after the last injection. At the 48-week visit after all study procedures were completed, all subjects, regardless of randomization assignment at baseline, were offered optional treatment if optimal aesthetic improvement was not maintained. If optional treatment was performed, 2, 4, and 12-week follow up visits were scheduled. Subjects were contacted by telephone 72 hours after each treatment (i.e. initial, touch up, optional retreatment at Week 48, as applicable) for safety follow-up.
The method of injection was at the discretion of the Treating Investigator. A sufficient amount of product was injected to achieve optimal correction of the midface, in the opinion of the Treating Investigator and subject. Optimal aesthetic result was defined as at least 1 MMVS point improvement from baseline and the best correction that could be achieved as agreed by the Treating Investigator and the subject. The maximum recommended injection volume per subject at the initial, touch-up, and re-treatment visits was 6.0 mL, for a maximum total volume of product injected of 18.0 mL.
Clinical Endpoints
With regards to safety, Restylane Contour in the cheek area was evaluated by: a) the incidence, intensity, and duration of predefined, expected post-treatment injection site reactions using a subject diary for 28 days after each treatment b) the incidence, intensity, duration, and onset of related AEs collected during the study, and c) cheek safety assessments as evaluated by a qualified study staff member at each visit. Vision function tests were performed before and after initial treatment and as applicable for the optional touch-up (Week 4) and re-treatment (Week 48). The vision function tests included the Snellen Visual Acuity test to assess visual acuity for distance vision;
Extraocular
Muscle Function test to examine the function of the eye muscle; and Confrontation Visual Field test to assess the subject’s peripheral vision. With regards to effectiveness, the primary analysis for cheek augmentation was evaluated based on demonstration of non-inferiority of Restylane Contour versus Control in cheek augmentation by comparing change from baseline in the Blinded Evaluator live assessment of midface fullness at 12 weeks after the last injection, using the validated Medicis Midface Volume Scale (MMVS) responder rates1
Directions For Assembly
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Assembly Of Needle To Syringe
Use surgical gloves, remove the cap from the needle and the tip cap from the syringe. Hold firmly around the syringe barrel and grasp the needle shield with the other hand. Screw the needle tight onto the syringe by simultaneously pushing and rotating firmly until the needle is complete locked. To ensure proper assembly, minimize the gap between the needle shield and the syringe.
See the figure below.
Remove the needle shield just before injection by pulling it straight out. Do not rotate.
Note: Improper assembly may cause leakage or needle disconnection.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully appraised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain the desired level of correction.
Treatment Procedures
-
Injection Technique
1. Restylane Contour is a cross-linked formulation resulting in a robust injectable gel that can be injected using a 27 G needle or a blunt tip TSK STERiGLIDE cannula (25-27 G, length 1.5 or 2 inches) for correction of midface contour deficiencies and cheek augmentation.
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully appraised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain the desired level of correction.
3. Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual field testing.
4. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
• ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines1
• identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal filler injection
• conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system deficits
5. Aseptic technique and standard practice to prevent cross infections should be observed at all times including the use of disposable gloves during the injection procedure. All traces of make-up below the level of the lower orbital rim should be removed prior to any injection. The treatment site should be cleaned with a suitable antiseptic solution.
6. To avoid breakage of the needle/cannula, do not attempt to bend or otherwise manipulate it before or during treatment. If needle/cannula gets bent, discard it and complete the procedure with a replacement needle/cannula. Do not re-shield used needles/cannula. Recapping by hand is a hazardous practice and should be avoided. Discard unshielded needles in approved sharps collectors.
7. Before injection, press the plunger rod carefully until a small droplet is visible at the tip of the needle and the plunger is at the 1mL graduation mark.
8. If a needle is used, after insertion and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not in a blood vessel. When using acannula, an entry point is made in the skin with an incision needle of appropriate size.
9. Inject slowly by gently pressing down on the plunger rod with the thumb or palm of the hand. Do not apply excessive pressure to the syringe at any time. Presence of scar tissue may impede advancement of the needle/cannula. If resistance is encountered the needle/cannula should be partially withdrawn and repositioned or fully withdrawn and checked for function and replaced if needed.
10. The injection technique may vary based on the subject’s treatment needs and the health care professional’s experience and preference. The techniques may include Linear antegrade threading, Linear retrograde threading, Serial puncture, Depot, Fan technique or Other.
11. Restylane Contour should be injected in the supraperiosteal zone or subcutaneous region of the midface. Care should be taken to avoid intramuscular injection. It is recommended to change needle/cannula for each new treatment site.
12. It is important that the injection is stopped just before the needle/cannula is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
13. It is recommended that the dose should not exceed 6 mL per treatment session. The recommended maximum injected volume per subject and treatment (touch-up volume included) is 12 mL.
14. Correct to 100% of the desired volume effect. Do not overcorrect.
15. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
16. After each injection, the midface should be observed to assess the degree of enhancement and the uniformity of the implant. The area should be gently palpated to ensure an even deposition of the implant. Palpated “skip areas” (areas not containing product) should be treated with additional implant material or by gentle massage of the area until a uniform implant is palpable.
17. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection should occur, the area should be firmly massaged between fingers to obtain optimal results. If the treated area is swollen directly after the injection, an ice pack can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anaesthetic to avoid thermal injury.
18. Patients may experience treatment site responses, which typically resolve within 1 to 2 weeks.
19. The health care practitioner should instruct the patient to promptly report any problems associated with the use of Restylane Contour.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane Contour?
Restylane Contour® is a dermal filler injected under the (facial) skin. Once in place, it helps restore volume of your midface. Restylane Contour may also be used to increase fullness of your cheeks.
Restylane Contour is made out of hyaluronic acid (HA) ‐ a naturally occurring sugar, found in the body that gives the skin moisture, volume and elasticity – and a small amount of lidocaine, which is a commonly used local anesthetic to numb the skin. Restylane Contour is crosslinked with BDDE, an ingredient that helps form a network of HA, to provide a gel filler that lasts longer at the treatment site.
What is Restylane Contour for?
As you age, your facial skin begins to lose its elasticity and volume. As a result, the face droops and shifts downwards and your facial features may become hollow.
Restylane Contour injectable gel is designed to temporarily restore volume to the midface and to add fullness to the cheeks in patients over the age of 21. Restylane Contour has been shown to maintain this effect for up to 12 months.
How is Restylane Contour used?
Restylane Contour is injected with a small needle or cannula under your facial skin.
Are there any reasons why I should not receive Restylane Contour?
Before using Restylane Contour, your doctor will talk to you about your medical history to determine if you are an appropriate candidate for treatment. You will be asked questions about possible allergies to ensure that Restylane Contour can be safely administered. Tell your doctor about all your medical conditions, including if you:
Have severe allergies with a history of severe reactions (anaphylaxis) or multiple severe allergies. Use of Restylane Contour may result in an allergic reaction.
Are allergic to the anesthetic lidocaine or to any of the proteins used to make the HA in Restylane Contour (bacterial proteins). Use may result in an allergic reaction.
If you are not sure about your medical history concerning these allergies or other medical conditions you think might be relevant, please discuss further with your doctor.
Safety
What precautions should my doctor discuss with me?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
- You should discuss the potential treatment risks and benefits with your doctor.
- Restylane Contour is only to be used for adults over the age of 21.
- Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. The safety of Restylane Contour has not been studied in women who are pregnant or breastfeeding.
- Tell your doctor if you are taking any medications used to decrease the body’s natural defense system (immunosuppressants). Restylane Contour injections may then result in an increased risk of infection.
- Tell your doctor if you have a bleeding disorder or are taking any medication that can thin your blood or prolong bleeding, such as aspirin and warfarin. As with any injection procedure this may increase your risk of bruising or bleeding at the injection site.
- Tell your doctor if you have a history of excessive scarring, particularly thick and stiff scars, or any skin color (pigmentation) disorders. Scarring and skin color changes can occur with injectable dermal fillers in general. When Restylane Contour was studied in patients with different skin tones (pale to dark), there were no reports by patients of excessive scarring (keloids) or changes in skin color.
- Tell your doctor if you have recently had skin therapies such as laser treatment, mechanical or chemical peels or hair removal. This may lead to increased risk of side effects such as redness, swelling, heat or pain of the skin.
- If you have had cold sores in the past, there is a risk that they will return after your procedure with Restylane Contour.
- Avoid or minimize hard (strenuous) exercise and exposure to extensive sun, UV lamps, indoor tanning beds/booths, or extreme temperatures within the first 24 hours after treatment with Restylane Contour. Any of these may cause temporary redness, swelling, pain and/or itching at the injection site.
- Tell your doctor immediately if you experience any changes in your vision, signs of a stroke, white appearance of the skin, or unusual pain during or shortly after treatment. These could be signs of an unintentional intravascular injection and require immediate medical care to avoid permanent complications. If you have any additional questions about any topic in this section, please discuss further with your doctor. See also Section 13 on when you should contact your doctor immediately after treatment.
Troubleshooting
You should call your doctor immediately if you have:
- Changes in your vision.
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion). (http://www.nlm.nih.gov/medlineplus/stroke.html)
- White appearance of the skin.
- Unusual pain during or shortly after treatment.
Be sure to call your doctor if you have:
- Persistent injection site reactions beyond 14 days, as most side effects such as bruising, swelling, pain, tenderness, redness, and itching will usually go away within one to two weeks.
- Blisters or skin sores that recur, which may signal the presence of a herpes infection.
- Any signs of infection such as fever, redness that spreads to surrounding areas, drainage, increasing tenderness or increasing pain that does not go away.
- Significant pain away from the injection site.
- Any side effect that occurs weeks or months after treatment.
- Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
The adverse event reports received from post-marketing surveillance (voluntary reporting and published literature) for the use of Restylane Contour with and without lidocaine from worldwide sources most commonly included reports of transient swelling/edema and with immediate onset or delayed onset, up to several weeks after treatment.
The following events were also reported in decreasing order of frequency:
• mass formation/induration
• pain/tenderness
• papules/nodules
• erythema
• inflammation
• short duration of effect
• presumptive bacterial infections and abscess formation
• bruising/hematoma
• ischemia and necrosis including pallor, due to unintentional intravascular injection or embolisation
• injection site reactions including warmth, burning sensation and exfoliation
• hypersensitivity/angioedema
• neurological symptoms including hypoaesthesia and paraesthesia
• granuloma/foreign body reaction
• device dislocation
• deformity/asymmetry
• discoloration
• eye disorders including eye pain and eyelid oedema
• symptoms of reactivation of herpes infection
• pruritus
• blisters/vesicles
• rash
• atrophy/scarring
• acne
• dermatitis
• encapsulation
• extrusion of device
• urticaria
• non-dermatological events including headache, discomfort, nausea and
• other dermatological events including chapped lips and hyperhidrosis When required, treatments for these events included corticosteroids, antibiotics, antihistamines, analgesics, NSAIDs, vasodilation agent, drainage or enzymatic degradation (with hyaluronidase) of the product.
Reports of serious adverse events for Restylane Contour with and without lidocaine are rare. The most commonly reported serious adverse events from post-marketing surveillance were ischemia/necrosis, infection/abscess and hypersensitivity/angioedema. Serious ischemia/necrosis was mostly reported with immediate onset up to a few days following the injection. The outcomes of ischemia/necrosis cases were mainly recovered or were recovering at the time of last contact. The treatments included hyaluronidase, analgesics, corticosteroids, vasodilation agent, antihistamine and aspirin.
Serious infection/abscess was reported with onset up to a week or a delayed onset up to a year following the injection. The outcome was mainly recovered or recovering at the time of last contact. The treatments included antibiotics, antihistamine, corticosteroids, hyaluronidase and drainage. Serious hypersensitivity/angioedema was mostly reported with immediate onset up to a few days following the injection. Almost all patients had recovered at the time of last contact. The treatments included antihistamine, analgesic, corticosteroids, hyaluronidase and sodium chloride.
Vascular compromise may occur due to an inadvertent intravascular injection or as a result of vascular compression associated with implantation of any injectable product. This may manifest as blanching, discolouration, necrosis or ulceration at the implant site or in the area supplied by the blood vessels affected; or rarely asischemic events in other organs due to embolization. Isolated rare cases of ischemic events affecting the eye leading to visual loss, and the brain resulting in cerebral infarction, following facial aesthetic treatments with dermal fillers have been reported. Reported treatments include anticoagulant, epinephrine, aspirin, hyaluronidase, corticosteroid treatment, analgesics, antibiotics, local wound care, drainage, surgery and hyperbaric oxygen.
Symptoms of inflammation at the implant site commencing either shortly after injection or after a delay of up to several weeks have been reported. In case of unexplained inflammatory reactions, infections should be excluded and treated if necessary since inadequately treated infections may progress into complications such as abscess formation. Treatment using only oral corticosteroids without concurrent antibiotic treatment is not recommended. The prolonged use of any medication, e.g., corticosteroids or antibiotics in treatment of adverse events has to be carefully assessed, since this may carry a risk for the patient. In case of persistent or recurrent inflammatory symptoms, consider removal of the product by aspiration/drainage, extrusion or enzymatic degradation (use of hyaluronidase has been described in scientific publications).
Before any removal procedure is performed, the swelling may be reduced by using e.g. NSAID for 2-7 days or a short course of corticosteroids for less than 7 days, in order to more easily palpate any remaining product. Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Galderma Laboratories, L.P. at 1-855-425-8722.
Post-treatment Checklist
What should I do after receiving treatment?
- Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- For the first 24 hours, you should avoid or minimize hard (strenuous) exercise. You should also avoid or minimize exposure to extensive sun or extreme temperatures. Exposure to any of these may cause the area where you were treated to temporarily become red, swell and/or itch. If you experience any of these, an ice pack can be applied for relief.
- Avoid taking aspirin, NSAID, St. John’s Wort, blood thinners, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site
User Assistance Information
If you believe that you have experienced a serious problem related to Restylane Contour you should call your doctor. Your questions about Restylane Contour can be personally answered by contacting the Galderma Laboratories L.P. toll‐free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday to through Friday.
1‐855‐425‐8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised: June
Restylane Eyelight
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Restylane Eyelight is a transparent, viscous, and sterile gel of hyaluronic acid (HA) generated by Streptococcus species of bacteria, chemically crosslinked with BDDE (1.4-butanediol diglycidyl ether). The gel is suspended in phosphate buffered saline pH 7 at a HA concentration of 20 mg/mL with 0.3% lidocaine.
Indication
Restylane Eyelight is indicated for the improvement of infraorbital hollowing in patients over the age of 21.
How Supplied
Restylane Eyelight is supplied in a disposable glass syringe with a luer‑lock fitting. Restylane Eyelight is co-packed with sterilized needle as indicated on the carton (29 G x ½").
A patient record label is a part of the syringe label. Remove it by pulling the flap marked with three small arrows. This label is to be attached to patient records to ensure traceability of the product.
The contents of the syringe are sterile.
The volume in each syringe and needle gauge is as stated on the syringe label and on the carton
Self Life and Storage
Restylane Eyelight must be used prior to the expiration date printed on the package. Store at a temperature of up to 25° C (77° F). Do not freeze. Protect from sunlight.
Refrigeration is not required.
Do not resterilize Restylane Eyelight as this may damage or alter the product.
Do not use if the package is open or damaged or if the expiry date or lot number is missing or illegible. Immediately return the damaged product to Galderma Laboratories, L.P.
Contraindications
- Restylane Eyelight is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- Restylane Eyelight contains trace amounts of gram positive bacterial proteins and is
contraindicated for patients with a history of allergies to such material. - Restylane Eyelight contains lidocaine and is contraindicated for patients with a history of allergies to such material or other amide type anesthetics.
Warnings
- Introduction of Restylane Eyelight into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in theface have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Defer use of Restylane Eyelight at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
- Restylane Eyelight must not be implanted into blood vessels and should not be used in vascular rich areas. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the periorbital area. It is thought to result from the injury, obstruction,
or compromise of blood vessels. Special caution should be taken if the patient has undergone a prior surgical procedure in the planned treatment area. - Patients with bleeding disorders or patients using substances that affect platelet function, thrombolytics or anticoagulants may, as with any injection, experience increased bruising or bleeding at injection site.
Precautions
• Restylane Eyelight is for single patient and single session use only and should be discarded immediately after use. Do not resterilize. Do not use if package is opened or damaged.
• Health care professionals are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
• In order to minimize the risks of potential complications, this product should only be used by health care professionals who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection in order to minimize the risks of potential complications (perforation or compression of vessels, nerves and other vulnerable structures).
• Based on U.S. clinical study, patients should be limited to up to 1 mL per side and treatment session in the infraorbital hollow area. If a volume of more than 1 mL per side is needed to achieve optimal correction, a follow-up treatment session isrecommended. The safety of injecting greater amounts per treatment session has not been established.
• The safety and effectiveness of cannula injection of Restylane Eyelight have only been clinically evaluated in one brand of blunt-tip cannulas (TSK STERIGLIDE) that are 25G27G and 1.5 inches in length.
• As with all transcutaneous procedures, Restylane Eyelight implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
• The safety of Restylane Eyelight for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
• Patients with abnormal wound healing or dark skin (Fitzpatrick Type IV-VI) may be more prone to develop hypertrophic scarring and keloid formation following dermal filler injections. Clinical studies in patients with Fitzpatrick Skin Types IV, V and VI in other indications with a similar gel, reported a 9% incidence of inflammatory hyperpigmentation and no reports of keloid formation.
• Injection of Restylane Eyelight in patients with pre-existing tendency toward edema formation may be associated with excessive swelling due to fluid build-up.
• Injection in the lower periorbital region in patients with pre-existing pigmented dark lower eyelid circles may be associated with more prominent discoloration.
• Injection of Restylane Eyelight too superficially and injection in facial areas with limited soft tissue support or soft tissue cover, or thin skin, such as the periorbital area, may result in contour irregularities and palpable lumps and/or bluish discolouration.
• Restylane Eyelight should be used with caution in patients on immunosuppressive therapy.
• Avoid injecting Restylane Eyelight into areas in close proximity to permanent implants, as this could potentially aggravate latent adverse events or interfere with the aesthetic outcome of the treatment. Limited data is available on injecting Restylane Eyelight into an area where an implant other than hyaluronic acid has been placed.
• The safety of Restylane Eyelight with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
• Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures at least until any initial swelling and redness has resolved.
• If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Restylane Eyelight, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Restylane Eyelight is administered before the skin has healed completely after such a procedure.
• Injection of Restylane Eyelight into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
• The product contains lidocaine. If other local anesthetics or agents structurally related to amide-type local anesthetics are used concurrently with the product the following considerations should be observed:
- Use with caution in patients with epilepsy, impaired cardiac conduction, severely impaired hepatic function or severe renal dysfunction
- Systemic toxic effects could be additive
- Peribulbar injections carry a low risk of persistent ocular muscle dysfunction
• Individual variation and treatment area may affect the biodegradation of injectable HA fillers and product might be detected in the tissue even after the clinical effect has disappeared.
• Restylane Eyelight is a clear, colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Galderma Laboratories, L.P. at 1-855 425-8722.
• Glass is subject to breakage under a variety of unavoidable conditions. Care should be taken with the handling of the glass syringe and with disposing of broken glass to avoid laceration or other injury.
• After use, syringes and needles/cannulas should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
• Restylane Eyelight should not be mixed with other products before implantation of the device.
Adverse Experiences
U.S. Pivotal study of Restylane Eyelight for correction of infraorbital hollows The U.S. randomized, controlled clinical study involved 333 subjects at 16 centers for correction of infraorbital hollows. The subjects were randomized to Restylane Eyelight (287 subjects) or no treatment (46 subjects). Subjects randomized to treatment with Restylane Eyelight, were treated at study start and were offered an optional touch-up treatment after one month. At Month 12 both the no-treatment control subjects and the treatment group subjects were offered an optional Restylane Eyelight treatment. Subjects were injected with a needle or a cannula. Subjects reported injection site reactions (IREs) in a 28-day paper diary following each performed treatment (initial treatment, optional touch-up and optional 12 Month treatment). Subject were to assess the presence of pre defined expected post-treatment events, i.e., swelling, redness, tenderness, pain (including burning), bruising, itching or lumps/bumps were assessed for the treated area and to rate the level of intensity (i.e., none, tolerable, affects daily activities, or disabling) for each of the pre-defined events (Table 1). Over 77,5% of the pre-defined IREs after injection with Restylane Eyelight (initial, touch-up and retreatment) were considered tolerable and over 63.7% lasted 7 days or less (Table 2).
Table 1: Pre-defined Injection Related Events (IREs) by Maximum Severity Occurring in Subjects After Injection
Tolerable
n (%)
Affects
Daily
Activities
n (%)
Disabling
n (%)
Total
n (%)
Post Initial Injection [1] (N=301)
Pain (including burning) 164 (91.1) 14 (7.9) 2 (1.1) 180 (59.8)
Tenderness 255 (94.4) 14 (5.2) 1 (0.4) 270 (89.7)
Redness 164 (88.6) 20 (10.8) 1 (0.5) 185 (61.5)
Bruising 153 (80.5) 35 (18.4) 2 (1.1) 190 (63.1)
Swelling 207 (80.9) 47 (18.4) 2 (0.8) 256 (85.0)
Lumps/Bumps 139 (86.3) 21 (13.0) 1 (0.6) 161 (53.5)
Itching 42 (97.7) 1 (2.3) 0 43 (14.3)
Post-optional Touch-up Injection [1] (N=206)
Pain (including burning) 98 (89.1) 12 (10.9) 0 110 (53.4)
Tenderness 152 (92.1) 13 (7.9) 0 165 (80.1)
Redness 110 (90.2) 11 (9.0) 1 (0.8) 122 (59.2)
Bruising 109 (86.5) 15 (11.9) 2 (1.6) 126 (61.2)
Swelling 141 (87.6) 18 (11.2) 2 (1.2) 161 (78.2)
Lumps/Bumps 85 (89.5) 10 (10.5) 0 95 (46.1)
Itching 24 (92.3) 2 (7.7) 0 26 (12.6)
Post-Retreatment Injection [1] (N = 153)
Pain (including burning) 77 (88.5) 10 (11.5) 0 87 (56.9)
Tenderness 111 (90.2) 12 (9.8) 0 123 (80.4)
Redness 72 (86.7) 11 (13.3) 0 83 (54.2)
Bruising 62 (77.5) 18 (22.5) 0 80 (52.3)
Swelling 97 (81.5) 20 (16.8) 2 (1.7) 119 (77.8)
Lumps/Bumps 65 (87.8) 9 (12.2) 0 74 (48.4)
Itching 22 (88.0) 3 (12.0) 0 25 (16.3)
Number of subjects who completed at least one diary entry and were injected.
Note 1: Percentages for symptom severity columns are based on the total number of subjects who reported 'Tolerable' or higher for a respective symptom in their subject diary; The total column percentages are based on the number of subjects who completed at least one diary entry and were injected.
Note 2: Maximum severity of both sides of the face is presented.
Note 3: Initial treatment includes subjects randomized to Restylane Eyelight that received a baseline injection plus subjects randomized to No Treatment that had an optional initial treatment; Optional touch-up includes subjects randomized to Restylane Eyelight that received an optional touch-up at one month; Retreatment includes subjects randomized to Restylane Eyelight that received an optional retreatment at Month 12.
Table 2: Duration of Pre-defined Injection Related Events (IREs) [1] Occurring in Subjects After Injection
1 Day
n (%)
2 - 7 Days
n (%)
8 - 13 Days
n (%)
14 - 28 Days
n (%)
Post-Initial Injection [2] (N=288)
Pain (including burning) 67 (37.2) 105 (58.3) 8 (4.4) 0
Tenderness 30 (11.1) 201 (74.4) 30 (11.1) 9 (3.3)
Redness 44 (23.8) 129 (69.7) 9 (4.9) 3 (1.6)
Bruising 24 (12.6) 105 (55.3) 45 (23.7) 16 (8.4)
Swelling 30 (11.7) 196 (76.6) 25 (9.8) 5 (2.0)
Lumps/Bumps 29 (18.0) 78 (48.4) 23 (14.3) 31 (19.3)
Itching 19 (44.2) 24 (55.8) 0 0
Post-Optional Touch-up Injection [2] (N=182)
Pain (including burning) 37 (33.6) 67 (60.9) 4 (3.6) 2 (1.8)
Tenderness 17 (10.3) 130 (78.8) 12 (7.3) 6 (3.6)
Redness 35 (28.7) 76 (62.3) 6 (4.9) 5 (4.1)
Bruising 19 (15.1) 65 (51.6) 31 (24.6) 11 (8.7)
Swelling 24 (14.9) 108 (67.1) 17 (10.6) 12 (7.5)
Lumps/Bumps 14 (14.7) 50 (52.6) 15 (15.8) 16 (16.8)
Itching 10 (38.5) 15 (57.7) 1 (3.8) 0
Post-Retreatment Injection [2] (N=131)
Pain (including burning) 24 (27.6) 58 (66.7) 5 (5.7) 0
Tenderness 19 (15.4) 85 (69.1) 14 (11.4) 5 (4.1)
Redness 26 (31.3) 48 (57.8) 7 (8.4) 2 (2.4)
Bruising 8 (10.0) 43 (53.8) 21 (26.3) 8 (10)
Swelling 15 (12.6) 86 (72.3) 12 (10.1) 6 (5.0)
Lumps/Bumps 10 (13.5) 45 (60.8) 11 (14.9) 8 (10.8)
Itching 14 (56.0) 11 (44.8) 0 0
[1] Number of days was defined as the sum of days when a sign/symptom was scored 'Tolerable' or higher, on either side of face.
[2] Number of subjects who completed at least one diary entry and were injected when a sign/symptom was scored ‘Tolerable’ or higher.
Note 1: Percentages are based on the total number of subjects who reported 'Tolerable' or higher for a respective symptom in their subject diary.
Note 2: Initial treatment includes subjects randomized to Restylane Eyelight that received a baseline injection plus subjects randomized to No Treatment that had an optional initial treatment; Optional touch-up includes subjects randomized to Restylane Eyelight that received an optional touch-up at one month; Retreatment includes subjects randomized to Restylane Eyelight that received an optional retreatment at Month 12. Adverse Events (AEs) were assessed and reported by the Treating Investigator at the follow-up visit throughout the study. 40/316 (12.7%) treated subjects experienced an AE considered related to treatment or product after initial treatment. The percentage of subjects who experienced related AEs was higher in subjects who were injected using cannula compared with subjects who were injected using needle, 20.9% (32/153) and 4.9% (8/163) respectively. Females and subjects with BMI less or equal to 25.4 experienced more related AEs (Table 3). The percentage of subjects who experienced related AEs was higher in subjects who were injected at multiple depths (supraperiosteal and other) compared with subjects who were injected supraperiosteally only, 29.2% and 11.3%, respectively. The percentage of subjects who experienced related AEs was higher in subjects who received local injection of anesthetics before treatment compared with subjects who received topical anesthetics, 20.9% and 9.9%, respectively.
Table 3: Related AEs per sex and BMI subgroups
Subgroup Subjects with related AEs after initial treatment including touch-up treatment (%)
Sex Female 14% (38/276)
Male 5% (2/40)
Body
Mass
Index
(BMI)
BMI <= 25.4 (n=154) 18% (28/154) BMI > 25.4
(n=161)
7% (12/161)
The most common treatment or product related AEs (occurring in at least 1% of the subjects) after initial treatment were injection-site swelling (3.8%), injection-site pain (2.5%), headache (2.2%) injection-site bruising (1.6%), injection-site mass (1.3%), and injection-site edema (1.3%). All related AEs were mild or moderate in severity. Ten (3.2%) subjects who received Restylane Eyelight experienced moderate events; all moderate events considered related to study product or injection procedure were resolved by the end of the study. In the clinical study, eight subjects had related AEs with an onset after 21 days. Two subjects experienced in total 3 AEs with moderate intensity (injection-site edema and injection-site swelling on left and right side), all other were of mild intensity. All but one of these (mild injection-site swelling) were resolved during the study. There were no treatment-related serious AEs reported in the study. Safety assessments such as visual acuity, confrontational visual fields, and ocular motility were evaluated throughout the study. The visual acuity assessments showed that over 97% of treatment group participants had no worsening (the same or better) from baseline to any assessment timepoints. Four (2.5%) subjects injected using needle reported AEs of special interest (AESIs), and thirteen (8.5%) subjects injected using cannula. For the AESIs, 25 events of visual acuity worsening were reported by 6% (19/316) of the treated subjects during the study. For 8 subjects (9 events) the visual acuity decline was maintained at the end of the study, with a maximum decline of a 2 line decrease from start to end of study. All the visual acuity changes were considered mild in intensity, and not related to the study product or injection procedure.
One subject experienced a light sensitivity in one eye that started 5 days after retreatment and lasted for 3 days before the event resolved, without any action taken. The event was considered mild in intensity and not related to study product.
Clinical Trials
-
Directions For Assembly
Syringe with white cap:
It is recommended to use medical gloves. Use your thumb and forefinger to hold firmly around both the syringe barrel and the luer-lock adapter part (C) of the closure system. With your other hand, take hold of the white cap (A) at the end of the closure system and gently tilt back and forth carefully until cap disconnects and can be pulled off (seal will be broken).
Do not rotate.
Do not touch the syringe tip (B) to keep it sterile.
Syringe with transparent cap:
Unscrew the tip cap of the syringe carefully.
Assembly Of Needle To Syringe
Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the luerlock adapter (C). Grasp the needle shield with the other hand. To facilitate proper assembly, both push and rotate firmly clockwise. Make sure the needle is screwed on all the way so that the needle shield touches the luer-lock adapter (C). To remove the needle shield, hold the syringe and the luer-lock adapter. With your other hand hold the needle shield and pull straight out. Do not rotate. Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the luer-lock and needle hub connection.
Assembly instruction also applies to cannulas.
Pre-Treatment Guidlines
Prior to treatment, the patient should avoid taking aspirin, nonsteroidal anti-inflammatory medications, St. John’s Wort, or high doses of Vitamin E supplements. These agents may increase bruising and bleeding at the injection site.
Treatment Procedures
1. Use of this product should be used by only qualified health care professionals with expertise in dermal filler injections.
2. Educational resources are available through myGAINtraining.com, which provides training on the anatomy of the treatment area, effective patient assessment, and appropriate injection techniques. Health care professionals may contact Galderma for educational and training resources specific to this indication.
3. Prior to treatment, a medical history should be obtained to do a proper patient selection. The patient shall be informed about the indications, contraindications, warnings, precautions, treatment responses, potential adverse events and method of administration. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain the desired level of correction.
4. Before and after treatment, health care professionals are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual field testing.
5. Health care professionals are encouraged to be prepared with the following in the event of an intravascular injection:
• ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines1
• identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal filler injection
• conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system deficits
6. The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with a suitable antiseptic solution. Medical gloves are recommended during the injection procedure.
7. To avoid breakage of the needle/cannula, do not attempt to bend or manipulate it before or during treatment. If it gets bent, discard it and complete the procedure with a replacement needle/cannula.
8. Before injecting, remove air by pressing the rod carefully until a small droplet is visible at the tip of the needle/cannula.
9. When using a needle, withdraw the plunger rod slightly to aspirate and verify that the needle is not intravascular. Inject slowly while pulling the needle backwards.
10. When using a cannula, after preparation as described above, an entry point is made in the skin with an incision needle of appropriate size. Inject slowly.
11. Restylane Eyelight is administered using a thin gauge needle (29 G x ½") or a blunt cannula. (25-27G with cannula length of 1.5 or 2 inches). Restylane Eyelight should be placed in the supraperiosteal plane. If Restylane Eyelight is injected too superficially this may result in visible lumps and/or bluish discoloration.
12. Inject Restylane Eyelight applying even pressure on the plunger rod. Do not apply excessive pressure to the syringe at any time. If resistance is encountered, the needle/cannula should be partially withdrawn and repositioned, or fully withdrawn, checked for function and replaced if needed. It is important that the injection is stopped just before the needle/cannula is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
13. For each new treatment site, it is recommended to change needle/cannula to minimize the risk of infections and to avoid the use of blunt needles.
14. Defects should be fully corrected, but not overcorrected. In the event of overcorrection, consider removal of excessive product by aspiration, extrusion or enzymatic degradation (use of hyaluronidase has been described in scientific publications).
15. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
16. The correction site can be gently massaged to conform to the contour of the surrounding tissues.
17. If the treated area is swollen directly after the injection, an ice pack with adequate protective cloth can be applied on the site for a short period. Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
18. Patients may experience treatment site responses, which typically resolve within 1 week.
19. Typical usage for each treatment session is specific to the site as well as hollow severity. Based on U.S. clinical studies, the maximum recommended dose per treatment is 1 mL per side for the infraorbital hollow area per treatment. If a volume of more than 1 mL per side is needed to achieve optimal correction, a follow-up treatment session is recommended.
Injection Technique
Restylane Eyelight can be injected by a number of different techniques; linear threading, serial puncture, fanning, micro bolus, or combination of these injection techniques. They depend on the treating physician’s experience and preference, and patient characteristics.
• Serial puncture (A) involves multiple, closely spaced injections. Although serial puncture allows precise placement of the filler, it produces multiple puncture wounds that may be undesirable to some patients.
• Linear threading (includes retrograde and antegrade) (B) is accomplished by fully inserting the needle into skin and injecting the filler along the track as a “thread.” Although threading is most commonly practiced after the needle has been fully inserted and is being withdrawn, it can also be performed while advancing the needle (“push-ahead” technique).
Note! The correct injection technique is crucial for the final result of the treatment.
A. Serial Puncture
B. Linear Threading
(includes retrograde and antegrade) If the infraorbital hollows need further treatment, the same procedure should be repeated until a satisfactory result is obtained. Additional treatment with Restylane Eyelight may be necessary to achieve the desired correction.
Sterile Needles
• Follow national, local or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
• To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
• Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided.
• Discard unshielded needles in approved sharps collectors.
• Restylane Eyelight is provided with a needle that does not contain engineered injury protection. Administration of Restylane Eyelight requires direct visualization and complete and gradual insertion of the needle making engineered protections infeasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is Restylane® Eyelight?
Restylane® Eyelight is a clear injectable gel composed of hyaluronic acid (HA), a natural substance that already exists in the body. Restylane® Eyelight is crosslinked with BDDE, an ingredient that helps form a network of HA to provide a gel filler that lasts longer. Restylane® Eyelight is non‐animal based and free from animal protein. Restylane® Eyelight contains 0.3% lidocaine. The lidocaine in Restylane® Eyelight is an anesthetic that has been added to reduce the discomfort associated with the treatment.
What is Restylane® Eyelight for?
As you age, your facial skin begins to lose its elasticity and volume. As a result, the face droops and shifts downwards and your facial features may appear as hollow, such as the area under your eyes. Restylane® Eyelight injectable gel is designed to temporarily restore volume to the hollows under the eyes in patients over the age of 21. Restylane® Eyelight is intended for patients that are beginning to see a hollow appearance under the eyes. Restylane® Eyelight has been shown to maintain this effect for up to 12 months.
What warnings should my DOCTOR advise me about?
To help you understand the treatment risks, your doctor should discuss the following:
One of the risks with using this product is the unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
The use of Restylane® Eyelight where skin sores, pimples, rashes, hives, cysts, or infections are present should be postponed until healing is complete. Use of Restylane® Eyelight where these are present could delay healing or make your skin problems worse.
Tell your doctor if you have a bleeding disorder or are taking any medication that can thin your blood or prolong bleeding, such as aspirin and warfarin. As with any injection procedure this may increase your risk of bruising or bleeding at the injection site.
After having the injection, seek immediate medical attention if you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment.
Are there any reasons why I should not receive Restylane® Eyelight?
Before using Restylane® Eyelight, your doctor will talk to you about your medical history to determine if you are an appropriate candidate for treatment. You will be asked questions about possible allergies to ensure that Restylane® Eyelight can be safely administered. Tell your doctor about all your medical conditions, including if you:
- Have severe allergies with a history of severe reactions (anaphylaxis) or multiple severe allergies.
- Have an allergy to the lidocaine.
- Have an allergy to any of the proteins used to make the HA in Restylane® Eyelight.
If you are not sure about your medical history concerning these allergies or other medical conditions you think might be relevant, please discuss further with your doctor.
Safety
What precautions should my doctor discuss with me?
The following are important treatment considerations for you to discuss with your doctor and understand to help avoid unsatisfactory results and complications.
- Restylane® Eyelight should be injected only into the undereye hollow area by doctors who have completed necessary training for this injection area.
- You should discuss the potential treatment risks and benefits including post treatment care considerations with your doctor.
- Restylane® Eyelight is only to be used for adults over the age of 21. Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. The safety of Restylane® Eyelight has not been studied in women who are pregnant or breastfeeding.
- Tell your doctor if you are taking any medications used to decrease the body’s natural defense system (immunosuppressants). This may lead to an increased risk of infection.
- Tell your doctor if you have a wound healing disorder or a history of excessive scarring, particularly thick and stiff scars, or any skin color (pigmentation) disorders. Scarring and skin color changes can occur with injectable dermal fillers in general.
- Tell your doctor if you have recently had skin therapies such as laser treatment, mechanical or chemical peels or hair removal. This may lead to increased risk of side effects such as redness, swelling, heat or pain of the skin.
- Tell your doctor if you have permanent implants close to the undereye hollow or other prior implants, as this could increase the risk of side effects or interfere with the aesthetic outcome of the treatment. If you have had cold sores in the past, there is a risk that they will return after your procedure with Restylane® Eyelight.
- You have a dental block or use topical lidocaine at the same time as the filler treatment. High doses of lidocaine could cause a toxic reaction. 5 If you have any additional questions about any topic in this section, please discuss further with your doctor. See also Section 14 on when you should contact your doctor immediately after treatment.
Troubleshooting
When should I call my doctor?
You should call your doctor immediately if you have:
- Changes in your vision.
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion) (http://www.nlm.nih.gov/medlineplus/stroke.html)
- White appearance of the skin.
- Unusual pain during or shortly after treatment. Be sure to call your doctor if you have:
- Persistent injection site reactions beyond 14 days, as most side effects such as bruising, swelling, pain, tenderness, redness, and itching will usually go away within one to two weeks.
- Blisters or skin sores that recur, which may signal the presence of a herpes infection.
- Any signs of infection such as fever, redness that spreads to surrounding areas, drainage, increasing tenderness or increasing pain that does not go away.
- Significant pain away from the injection site.
- Any side effect that occurs weeks or months after treatment.
- Any other symptoms that cause you concern.
Administration
-
Post Marketing Surveillance
The adverse event reports received from post-marketing surveillance (from voluntary reporting and published literature) for the use of Restylane Eyelight with and without lidocaine, for infraorbital hollowing in the U.S. and other countries, most commonly included reports of transient swelling/edema and inflammatory reactions with immediate onset or delayed onset, up to several weeks after treatment.
The following events were also reported in decreasing order of frequency:
• mass formation/induration,
• erythema,
• bruising/bleeding,
• pain or tenderness,
• discoloration/hyperpigmentation,
• papules or nodules
• asymmetry/deformity
• short duration of effect,
• presumptive bacterial infections and abscess formation including cellulitis and purulent discharge,
• other injection site reactions and skin reactions including burning sensation, dryness, discomfort, exfoliation, irritation and warmth,
• eye disorders such as dry eye, eye swelling, increased lacrimation, eyelid ptosis, and visual impairment including blurred vision and blindness,
• hypersensitivity,
• pruritus,
• neurological symptoms including hypoesthesia, paraesthesia,
• scarring,
• ischemia and necrosis due to unintentional intravascular injection or embolisation,
• granuloma/foreign body reaction,
• device dislocation,
• rash,
• discharge/extrusion of device,
• urticaria,
• blisters/vesicles,
• dermatitis,
• capillary disorders such as telangiectasia,
• acne,
• muscle twitching and muscle weakness,
• encapsulation,
• symptoms of reactivation of herpes infection,
• dermatophytosis,
• other dermatological events including dry skin and skin wrinkling
• non-dermatological events including malaise, headache, pyrexia, sinusitis. When required, treatments for these events included ice, massage, warm compress, nitroglycerine paste, corticosteroids, antibiotics, antihistamines, analgesics, antiviral agents, diuretic agents, aspiration/incision drainage, surgery or enzymatic degradation (with hyaluronidase) of the product.
Reports of serious adverse events for Restylane Eyelight are rare. The most commonly reported serious adverse events were infection/abscess, swelling, mass, hypersensitivity/allergic reactions and ischemia/necrosis. Other concurrent serious events included: pain/tenderness, erythema and bruising. Serious infections/abscesses were mostly reported with a time to onset ranging from a few days up to 2 months following the injection. The infections usually resolved after three months and most of the patients had recovered or were recovering at the time of last contact. The treatments included; antibiotics, analgesics and corticosteroids .
Serious swelling was mostly reported with a time to onset ranging from a day to a few months. Most of the patients had recovered or were recovering at the time of last contact. The treatments included; corticosteroids, antibiotics and hyaluronidase. Serious mass was reported with a time to onset ranging from two weeks to a year. The outcome usually was recovered or recovering at the time of last contact. The treatments included: analgesics, antihistamine, antibiotics, corticosteroids and hyaluronidase.
The onset of serious hypersensitivity/allergic reactions generally varied from immediately to a few weeks post injection. The majority of the events were recovering or recovered at the time of last contact. The treatments included analgesics, antihistamine, antibiotics, and corticosteroids. Vascular occlusion resulting in ischemia/necrosis and visual disturbances including blindness have been reported following injection of any soft tissue filler in the face especially in the nose, glabella, periorbital areas, nasolabial folds, and cheek, with a time to onset ranging from immediate to a few weeks following injection. Vascular compromise may occur due to an inadvertent intravascular injection or as a result of vascular compression associated with implantation of any injectable product. This may manifest as blanching, discoloration, necrosis or ulceration at the implant site or in the area supplied by the blood vessels affected; or rarely as ischemic events in other organs due to embolisation. Isolated rare cases of ischemic events affecting the eye leading to visual loss, and the brain resulting in cerebral infarction, following facial aesthetic treatments have been reported. Reported treatments include anticoagulant, epinephrine, aspirin, hyaluronidase, steroid treatment, analgesics, antibiotics, local wound care, drainage, surgery and hyperbaric oxygen. Outcome of the events ranged from resolved to ongoing at the time of last contact. In many of the events requiring medical intervention the patient was injected into the highly vascularized areas of the glabella, nose, and periorbital area, which are outside the device indications for use (See Warnings section).
Late-onset adverse events (greater than 2 years after injection with dermal fillers), such as delayed-onset inflammation or granulomas, in the infraorbital region following treatment with Restylane fillers is low but, have been reported. Adverse events, such as puffiness, lumps, or swelling, have resulted in negative cosmetic outcomes, but, these presentations were noted as rare as well as correctable.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Galderma Laboratories, L.P. at 1-855-425-8722
Post-treatment Checklist
What should I do after receiving treatment?
- Avoid touching the treated area within six hours following treatment so you do not accidentally injure your skin while the area is numb. After that, the area can be gently washed with soap and water.
- For the first 24 hours, you should avoid or minimize hard (strenuous) exercise. You should also avoid or minimize exposure to extensive sun or extreme temperatures. Exposure to any of these may cause the area where you were treated to temporarily become red, swell and/or itch. If you experience any of these, an ice pack can be applied for relief.
- Avoid taking aspirin, NSAID, blood thinners, and high doses of Vitamin E supplements for one week after treatment. These agents may increase bruising and bleeding at the injection site.
ALTERNATIVE PROCEDURES
What other treatments are available to me?
There are other dermal filler gels in the United States that are available to you for treatment. Additionally, there are alternative treatments such as surgical procedures, implants or fat injections. You can discuss these treatments with your doctor to determine which one is right for you.
User Assistance Information
If you believe that you have experienced a serious problem related to Restylane® Eyelight you should call your doctor. Your questions about Restylane® Eyelight can be personally answered by contacting the Galderma Laboratories L.P. toll‐free call center between 8:00 a.m. and 5:00 p.m. Central Daylight Time, Monday through Friday.
1‐855‐425‐8722
Galderma (logo)
Restylane and Galderma are registered trademarks.
Revised 05/2023
Juvederm Ultra
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® Ultra injectable gel is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. JUVÉDERM® Ultra injectable gel consists of crosslinked hyaluronic acid (HA) produced by Streptococcus species of bacteria, formulated to a concentration of 24 mg/mL and suspended in a physiologic buffer.
Indication
JUVÉDERM® Ultra injectable gel is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
How Supplied
JUVÉDERM® Ultra injectable gel is supplied in individual treatment syringes with 30-G needles for single-patient use and ready for injection (implantation). The volume in each syringe is as stated on the syringe label and on the carton.
The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged.
Self Life and Storage
JUVÉDERM® Ultra injectable gel must be used prior to the expiration date printed on the label.
Store at room temperature (up to 25°C/77ºF). DO NOT FREEZE.
JUVÉDERM® Ultra injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan® Product Support immediately at 1-877-345 5372.
To place an order, contact Allergan® at 1-800-377-7790.
Contraindications
- JUVÉDERM® Ultra injectable gel is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® Ultra injectable gel contains trace amounts of Gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
Warnings
- JUVÉDERM® Ultra injectable gel must not be injected into blood vessels. Introduction of JUVÉDERM® Ultra injectable gel into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue llers; for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue llers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur (see Health Care Professional Instructions #10).
- Use of JUVÉDERM® Ultra injectable gel at speci c sites in which an active in ammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection procedure reaction to JUVÉDERM® Ultra injectable gel has been observed as consisting mainly of short-term in ammatory symptoms starting early after treatment and with less than 7 days’ duration. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® Ultra injectable gel is packaged for singlepatient use. Do not resterilize. Do not use if package is opened or damaged.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness of JUVÉDERM® Ultra injectable gel for the treatment of anatomic regions other than facial wrinkles and folds (eg, lips) have not been established in controlled clinical studies.
- As with all transcutaneous procedures, JUVÉDERM® Ultra injectable gel implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® Ultra is to be used as supplied. Modi cation or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product, and it can therefore no longer be assured.
- The safety of JUVÉDERM® Ultra injectable gel for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been established.
- The safety of JUVÉDERM® Ultra injectable gel in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- JUVÉDERM® Ultra injectable gel should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-in ammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® Ultra injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan® Product Support at 1-877-345-5372.
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® Ultra injectable gel, there is a possible risk of eliciting an in ammatory reaction at the implant site. This also applies if JUVÉDERM® Ultra injectable gel is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A. Clinical Evaluation of JUVÉDERM® Ultra injectable gel In a randomized, controlled clinical trial to evaluate safety and effectiveness, 146 subjects were injected with JUVÉDERM® Ultra injectable gel in one nasolabial fold (NLF) and ZYPLAST® dermal ller in the contralateral NLF. Preprinted diary forms were used by subjects to record speci c signs and symptoms experienced during each of the rst 14 days (Day 0 through Day 13) after initial and touch-up treatments. Subjects were instructed to rate each common treatment response listed on the diary as “Mild,” “Moderate,” “Severe,” or “None.” Injection site responses reported by > 5% of subjects in either treatment group are summarized in Tables 1 and 2.
Table 1. Injection Site Responses by Maximum Severity Occurring in > 5% of Treated Subjects
(Number/% of Subject NLFs)
Injection Site Responses
TOTALS JUVÉDERM® Ultra
(Na = 146 NLFs)
ZYPLAST®
(Na = 146 NLFs)
JUVÉDERM®
Ultra
nc %
ZYPLAST
nc %
Mild
nc %
Modb
nc %
Severe
nc %
Mild
nc %
Modb
nc %
Severe
nc %
Redness 136
93%
130
89%
72
49%
48
33%
16
11%
69
47%
45
31%
16
11%
Pain/
Tenderness
131
90%
128
88%
74
51%
45
31%
12
8%
87
60%
34
23%
7
5%
Firmness 129
88%
127
87%
66
45%
53
36%
10
7%
60
41%
56
38%
11
8%
Swelling 125
86%
122
84%
60
41%
54
37%
11
8%
77
53%
37
25%
8
5%
Lumps/Bumps 115
79%
122
84%
61
42%
45
31%
9
6%
66
45%
42
29%
14
10%
Bruising 86
59%
80
55%
43
29%
29
20%
14
10%
47
32%
27
18%
6
4%
Itching 52
36%
53
36%
42
29%
5
3%
5
3%
43
29%
7
5%
3
2%
Discoloration 48
33%
49
34%
31
21%
11
8%
6
4%
31
21%
15
10%
3
2%
a
Number of subject NLFs treated with the respective device
b Mod = Moderate
c
Number of subject NLFs with each specifi c injection site response
Table 2. Duration of Injection Site Responses
Occurring in > 5% of Treated Subjects
(Number/% of Subject NLFs)
Injection Site
Responses
JUVÉDERM® Ultra
(Na = 146 NLFs)
nb %
ZYPLAST®
(Na = 146 NLFs)
nb %
Durationc ≤ 3
Days
4-7
Days
8-14
Days
> 14
Days
≤ 3
Days
4-7
Days
8-14
Days
> 14
Days
Redness 60
41%
50
34%
8
5%
18
12%
46
32%
46
32%
10
7%
28
19%
Pain/
Tenderness
61
42%
46
32%
18
12%
6
4%
49
34%
53
36%
14
10%
12
8%
Firmness 29
20%
34
23%
20
14%
46
32%
25
17%
28
19%
20
14%
54
37%
Swelling 38
26%
48
33%
22
15%
17
12%
54
37%
38
26%
20
14%
10
7%
Lumps/Bumps 26
18%
32
22%
18
12%
39
27%
16
11%
18
12%
19
13%
69
47%
Bruising 29
20%
28
19%
24
16%
5
3%
35
24%
27
18%
10
7%
8
5%
Itching 25
17%
15
10%
7
5%
5
3%
21
14%
17
12%
4
3%
11
8%
Discoloration 22
15%
12
8%
4
3%
10
7%
26
18%
9
6%
3
2%
11
8%
a
Number of subject NLFs treated with the respective device
b Number of subject NLFs with each specifi c injection site response by maximum duration
c
Duration refers to number of days from symptom onset until resolution, irrespective of date of implantation Local injection site responses were recorded in subjects’ diaries one or more times for 99% of JUVÉDERM® Ultra injectable gel–treated NLFs and 98% of ZYPLAST® dermal
ller–treated NLFs. Subjects’ scores for both products were predominantly Mild or Moderate in intensity, and their duration was short lasting (7 days or less). JUVÉDERM® Ultra injectable gel injection site responses reported by greater than 1% of subjects and not noted in the above tables were skin dryness and peeling. No clinically meaningful differences in the safety pro les of JUVÉDERM® Ultra injectable gel and ZYPLAST® dermal ller were found during the study.
Directions For Assembly
-
Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe as shown in Figure A.
STEP 2: Insert needle
Hold the syringe body and rmly insert the hub of the needle (provided in the JUVÉDERM® package) into the LUER LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle by turning it rmly in a clockwise direction (see Figure B) until it is seated in the proper position as shown in Figure C.
NOTE: If the position of the needle cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle cap in the other. Without twisting, pull in opposite directions to remove the needle cap as shown in Figure E.
Pre-Treatment Guidlines
-
Treatment Procedures
-
Injection Technique
1. JUVÉDERM® Ultra injectable gel is a highly crosslinked formulation that can be injected using a 30-G needle for more versatility in contouring and volumizing of facial wrinkles and folds. Prior to treatment with JUVÉDERM® Ultra injectable gel, the patient’s medical history should be obtained and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
2. The patient’s soft-tissue de ciencies should be characterized with regard to etiology, distensibility, stress at the site, and depth of lesion. Depending on the type of skin, best results are obtained when the defect is readily distensible and correction can be visualized by manual manipulation (stretching) of the skin. Pretreatment photographs are recommended.
3. Topical or injectable anesthesia may be used to manage pain during and after injection.
4. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should
be swabbed with alcohol or other antiseptic. Prior to injecting JUVÉDERM® Ultra injectable gel, depress the plunger rod until the product ows out of the needle.
5. The injection technique of JUVÉDERM® Ultra injectable gel with regard to the angle and orientation of the bevel, the depth of injection, and the quantity administered
may vary. A linear threading technique, serial puncture injections, or a combination of the two have been used to achieve optimal results. If JUVÉDERM® Ultra injectable gel is injected too super cially, this may result in visible lumps and/or discoloration.
6. Inject JUVÉDERM® Ultra injectable gel applying even pressure on the plunger rod while slowly pulling the needle backward. The wrinkle should be lifted and eliminated by the end of the injection. It is important that the injection is stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too supercially in the skin
7. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle.
8. The typical total volume of JUVÉDERM® Ultra injectable gel to achieve optimal correction is 1.6 mL per treatment site. The typical volume of JUVÉDERM® Ultra injectable gel to achieve optimal correction for repeat treatment is 0.7 mL per treatment site.
Sterile Needles
-
PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® Ultra injectable gel is a colorless hyaluronic acid gel that is injected into facial tissue to smooth wrinkles and folds, especially around the nose and mouth. Hyaluronic acid is a naturally occurring sugar found in the human body. The role of hyaluronic acid in the skin is to deliver nutrients, hydrate the skin by holding in water, and to act as a cushioning agent.
What does it do?
JUVÉDERM® Ultra injectable gel temporarily adds volume to facial tissue and restores a smoother appearance to the face.
How is it used?
JUVÉDERM® Ultra injectable gel is injected into areas of facial tissue where moderate to severe facial wrinkles and folds occur. JUVÉDERM® Ultra injectable gel temporarily adds volume to the skin and may give the appearance of a smoother surface.
What will it accomplish?
JUVÉDERM® Ultra injectable gel will help to smooth moderate to severe facial wrinkles and folds. Most patients need one treatment to achieve optimal wrinkle smoothing, and the results last about 9 months to 1 year.
What are possible side effects?
Most side effects are mild or moderate in nature, and their duration is short lasting (7 days or less). The most common side effects include, but are not limited to, temporary injection-site responses such as: redness, pain/tenderness, firmness, swelling, lumps/ bumps, bruising, itching, and discoloration. As with all skin injection procedures, there is a risk of infection. One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
Are there any reasons why I should not receive JUVÉDERM® Ultra injectable gel?
Your physician will ask about your medical history to determine if you are an appropriate candidate for treatment. JUVÉDERM® Ultra injectable gel should not be used in patients who have:
• Severe allergies marked by a history of anaphylaxis or history or presence of multiple severe allergies
• Patients with a history of allergies to Gram-positive bacterial proteins
What should my physician advise me about?
The following are important treatment considerations for you to discuss with your physician and understand in order to help avoid unsatisfactory results and complications.
• Patients who are using substances that can prolong bleeding, such as aspirin or ibuprofen, as with any injection, may experience increased bruising or bleeding at the injection site. You should inform your physician before treatment if you are using these types of substances.
• If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® Ultra injectable gel, there is a possible risk of an inflammatory reaction at the treatment site
• JUVÉDERM® Ultra injectable gel should be used with caution in patients on immunosuppressive therapy, or therapy used to decrease the body’s immune response, as there may be an increased risk of infection
• The safety of JUVÉDERM® Ultra injectable gel for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been established
• The safety of JUVÉDERM® Ultra injectable gel in patients with a history of excessive scarring (eg, hypertrophic scarring and keloid formations) and pigmentation disorders has not been studied
What should my physician warn me about?
The safety and effectiveness of JUVÉDERM® Ultra injectable gel for the treatment of areas other than facial wrinkles and folds (such as lips) have not been established in controlled clinical studies.
Safety
-
Troubleshooting
Call your doctor immediately if you have:
1) Changes in your vision,
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headaches, dizziness, or confusion),
3) White appearance of the skin, or
4) Unusual pain during or shortly after treatment Be sure to also call your doctor if you have:
1) Any significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment
4) Any other symptoms that cause you concern.
Administration
-
Post Marketing Surveillance
The following adverse events were received from postmarket surveillance for JUVÉDERM Ultra and Ultra Plus, with and without lidocaine, with a frequency of 5 events or more and were not observed in the clinical study; this includes reports received globally from all sources including scienti c journals and voluntary reports. All adverse events obtained through postmarket surveillance are listed in order of number of reports received: edema, hematoma, non-in ammatory nodule, lack or loss of correction, in ammatory reaction, unsatisfactory result, skin discoloration, pain, allergic reaction, device migration, vascular occlusion, overcorrection, neurological symptoms such as increase or decrease in sensation, blister, infection, dry skin, dermatitis, in ammatory nodule/granuloma, bleeding, anxiety, abscess, headache, varied injuries, herpes, malaise, vision abnormalities, extrusion, u-like symptoms, acne, angioedema, necrosis, scarring, telangiectasia, dyspnea, nausea, dizziness, anaphylactic reaction, drainage, beading, syncope, deeper wrinkle, traumatic injury, depression, cyst, cardiac complications, autoimmune disorder exacerbation, calci cation, and vision loss. In many cases, the symptoms resolved without any treatment. Reported treatments have included: antibiotics, steroids, steroidal creams, hyaluronidase, anti-in ammatories, antihistamines, needle aspiration and drainage, ultrasound therapy, analgesics, anti-viral, excision, eye drops, hyperbaric oxygen, laser resurfacing, tissue debridement, surgical scar revision, ice, massage, warm compress, anticholinergics, vasodilators, arnica, petroleum jelly, anxiolytics, antifungals, anticoagulants, and epinephrine.
Vascular occlusion of vessels resulting in necrosis and vision abnormalities have been reported following injection of JUVÉDERM® products, with and without lidocaine, with a time to onset ranging from immediate to within one week following injection. These reported events likely resulted from inadvertent arterial injection. In many of these cases, the product was injected into the highly vascularized areas of the glabella, nose, and periorbital area, which are outside the device indications for use (see WARNINGS section). Reported treatments include: anticoagulants, epinephrine, aspirin, hyaluronidase, steroid treatment, eye drops, hyperbaric oxygen, surgery, vasodilators, and warm compress. Outcomes have ranged from completely resolved to ongoing at the time of last contact. Delayed-onset in ammation near the site of dermal ller injections is one of the known adverse events associated with dermal llers. Cases of delayed-onset in ammation have been reported to occur at the dermal ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in ammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Allergan® Product Surveillance Department at 1-877-345-5372.
Post-treatment Checklist
-
User Assistance Information
You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
For further questions and information, please call 1-800-766-017
Irvine, CA 92612 USA
1-800-624-4261
Made in France
Juvederm Ultra XC
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® Ultra XC is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of cross-linked hyaluronic acid (HA) produced by Streptococcus species of bacteria, formulated to a concentration of 24 mg/mL and 0.3% w/w lidocaine in a physiologic buffer.
Indication
- JUVÉDERM® Ultra XC injectable gel is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
- JUVÉDERM® Ultra XC is indicated for injection into the lips and perioral area for lip augmentation in adults over the age of 21.
How Supplied
JUVÉDERM® Ultra XC injectable gel is supplied in individual treatment syringes with 30-G needles for single-patient use and ready for injection (implantation). The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged.
Self Life and Storage
JUVÉDERM® Ultra XC injectable gel must be used prior to the expiration date printed on the label. Store at room temperature (up to 25°C/77°F). DO NOT FREEZE. JUVÉDERM® Ultra XC injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan® Product Support immediately at 1-877-345-5372.
To place an order, contact Allergan® at 1-800-377-7790.
Contraindications
- JUVÉDERM® Ultra XC is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® Ultra XC contains trace amounts of Gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® Ultra XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- The product must not be injected into blood vessels. Introduction of JUVÉDERM® Ultra XC into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft-tissue fillers; for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see Health Care Professional Instructions #13).
- Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection site reactions consist mainly of short-term inflammatory symptoms starting early after treatment and lasting ≤ 7 days in facial wrinkles and folds, and typically last ≤ 14 days in the lips. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® Ultra XC is packaged for single-patient use. Do not resterilize. Do not use if package is opened or damaged.
- In order to minimize the risks of potential complications, this product should only be used by health care professionals who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft-tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness for the treatment of anatomic regions other than facial wrinkles and folds, lips, and perioral area have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® Ultra XC is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product and it can therefore no longer be assured.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- JUVÉDERM® Ultra XC should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® Ultra XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan® Product Support at 1-877-345-5372.
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® Ultra XC, there is a possible risk of eliciting an inflammatory reaction at the implant site. An inflammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A 2-week, randomized, controlled U.S. clinical study for JUVÉDERM® Ultra XC compared with JUVÉDERM® Ultra without lidocaine showed a similar safety profile in all subjects (N = 36), with the exception of fewer reports of pain/tenderness with the product containing lidocaine. Common treatment site responses by severity and duration, are resented in Tables 1 and 2. Aside from injection site responses, there were no adverse events related to the device, procedure, or anesthesia.
• The most common injection site responses for JUVÉDERM®
Ultra XC were redness, swelling, tenderness, firmness, lumps/
bumps, discoloration, and bruising.
Table 1. Injection Site Responses by Maximum Severity
(Number/% of Subject NLFs)
Injection Site
Responses
TOTALS JUVÉDERM® Ultra XC
(Na = 36 NLFs)
JUVÉDERM® Ultra
(Na = 36 NLFs)
JUVÉDERM®
Ultra XC
nc
%
JUVÉDERM®
Ultra
nc
%
Mild
nc
%
Modb
nc
%
Severe
nc
%
Mild
nc
%
Modb
nc
%
Severe
nc
%
Redness 29
81%
30
83%
22
61%
7
19%
0
0%
21
58%
9
25%
0
0%
Pain 17
47%
22
61%
12
33%
5
14%
0
0%
16
44%
5
14%
1
3%
Tenderness 22
61%
29
81%
18
50%
3
8%
1
3%
22
61%
6
17%
1
3%
Firmness 32
89%
33
92%
22
61%
8
22%
2
6%
24
67%
9
25%
0
0%
Swelling 30
83%
29
81%
23
64%
6
17%
1
3%
17
47%
12
33%
0
0%
Lumps/Bumps 20
56%
22
61%
13
36%
6
17%
1
3%
17
47%
4
11%
1
3%
Bruising 27
75%
24
67%
16
44%
8
22%
3
8%
15
42%
6
17%
3
8%
Itching 12
33%
11
31%
12
33%
0
0%
0
0%
10
28%
1
3%
0
0%
Discoloration 22
61%
21
58%
17
47%
2
6%
3
8%
16
44%
3
8%
2
6%
a
Number of subject NLFs treated with the respective device
b
Mod = Moderate
c
Number of NLFs with any occurrence of a particular ISR (or severity for the overall percentages)
Table 2. Duration of Injection Site Responses
(Number/% of Subject NLFs)
Injection Site Responses JUVÉDERM® Ultra XC
(Na
= 36 NLFs)
nb
%
JUVÉDERM® Ultra
(Na
= 36 NLFs)
nb
%
Durationc 1-3
Days
4-7
Days
8-14
Days
> 14
Days
1-3
Days
4-7
Days
8-14
Days
> 14
Days
Redness 22
61%
4
11%
1
3%
2
6%
22
61%
4
11%
2
6%
2
6%
Pain 15
42%
0
0%
1
3%
1
3%
18
50%
3
8%
0
0%
1
3%
Tenderness 14
39%
3
8%
3
8%
2
6%
23
64%
5
14%
0
0%
1
3%
Firmness 15
42%
7
19%
5
14%
5
14%
15
42%
7
19%
8
22%
3
8%
Swelling 19
53%
7
19%
2
6%
2
6%
17
47%
7
19%
3
8%
2
6%
Lumps/Bumps 10
28%
4
11%
2
6%
4
11%
11
31%
5
14%
3
8%
3
8%
Bruising 12
33%
8
22%
4
11%
3
8%
7
19%
8
22%
6
17%
3
8%
Itching 8
22%
3
8%
0
0%
1
3%
9
25%
1
3%
0
0%
1
3%
Discoloration 13
36%
2
6%
4
11%
3
8%
10
28%
5
14%
4
11%
2
6%
a
Number of subject NLFs treated with the respective device
b
Number of subject NLFs with each specific ISR by maximum duration
c Duration refers to number of days from symptom onset until resolution, irrespective of date of implantation
B. Clinical Evaluation of JUVÉDERM® Ultra (Without Lidocaine) in the NLFs In the initial randomized, controlled clinical trial to evaluate safety and effectiveness, 146 subjects were injected with JUVÉDERM® Ultra in one NLF and ZYPLAST® dermal filler in the contralateral NLF. Preprinted diary forms were used by subjects to record specific signs and symptoms experienced during each of the first 14 days (day 0 through day 13) after initial and touch-up treatments. Subjects were instructed to rate each common treatment response listed on the diary as “Mild,” “Moderate,”
“Severe,” or “None.” Injection site responses reported by >5%
of subjects in either treatment group are summarized in Tables 3 and 4.
Table 3. Injection Site Responses by Maximum Severity
Occurring in > 5% of Treated Subjects
(Number/% of Subject NLFs)
Injection Site
Responses
TOTALS JUVÉDERM® Ultra
(Na = 146 NLFs)
ZYPLAST®
(Na = 146 NLFs)
JUVÉDERM®
Ultra
nc
%
ZYPLAST®
nc
%
Mild
nc
%
Modb
nc
%
Severe
nc
%
Mild
nc
%
Modb
nc
%
Severe
nc
%
Redness 136
93%
130
89%
72
49%
48
33%
16
11%
69
47%
45
31%
16
11%
Pain/
Tenderness
131
90%
128
88%
74
51%
45
31%
12
8%
87
60%
34
23%
7
5%
Firmness 129
88%
127
87%
66
45%
53
36%
10
7%
60
41%
56
38%
11
8%
Swelling 125
86%
122
84%
60
41%
54
37%
11
8%
77
53%
37
25%
8
5%
Lumps/Bumps 115
79%
122
84%
61
42%
45
31%
9
6%
66
45%
42
29%
14
10%
Bruising 86
59%
80
55%
43
29%
29
20%
14
10%
47
32%
27
18%
6
4%
Itching 52
36%
53
36%
42
29%
5
3%
5
3%
43
29%
7
5%
3
2%
Discoloration 48
33%
49
34%
31
21%
11
8%
6
4%
31
21%
15
10%
3
2%
a
Number of subject NLFs treated with the respective device
b
Mod = Moderate
c
Number of subject NLFs with each specific ISR
Table 4. Duration of Injection Site Responses
Occurring in > 5% of Treated Subjects
(Number/% of Subject NLFs)
Injection Site
Responses
JUVÉDERM® Ultra
(Na
= 146 NLFs)
nb
%
ZYPLAST®
(Na
= 146 NLFs)
nb
%
Durationc ≤ 3
Days
4-7
Days
8-14
Days
> 14
Days
≤ 3
Days
4-7
Days
8-14
Days
> 14
Days
Redness 60
41%
50
34%
8
5%
18
12%
46
32%
46
32%
10
7%
28
19%
Pain/
Tenderness
61
42%
46
32%
18
12%
6
4%
49
34%
53
36%
14
10%
12
8%
Firmness 29
20%
34
23%
20
14%
46
32%
25
17%
28
19%
20
14%
54
37%
Swelling 38
26%
48
33%
22
15%
17
12%
54
37%
38
26%
20
14%
10
7%
Lumps/Bumps 26
18%
32
22%
18
12%
39
27%
16
11%
18
12%
19
13%
69
47%
Bruising 29
20%
28
19%
24
16%
5
3%
35
24%
27
18%
10
7%
8
5%
Itching 25
17%
15
10%
7
5%
5
3%
21
14%
17
12%
4
3%
11
8%
Discoloration 22
15%
12
8%
4
3%
10
7%
26
18%
9
6%
3
2%
11
8%
a
Number of subject NLFs treated with the respective device
b
Number of subject NLFs with each specific ISR by maximum duration
c Duration refers to number of days from symptom onset until resolution, irrespective of date of implantation
Local injection site responses were recorded in subjects’ diaries one or more times for 99% of JUVÉDERM® Ultra treated NLFs and 98% of ZYPLAST® treated NLFs. Subjects’ scores for both products were predominantly Mild or Moderate in intensity, and their duration was short lasting (7 days or less). JUVÉDERM® Ultra injection site responses reported by greater than 1% of subjects and not noted in the above tables were skin dryness and peeling.
No clinically meaningful differences in the safety profiles of JUVÉDERM® Ultra and ZYPLAST® were found during the study.
Clinical Trials
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Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe as shown in Figure A.
STEP 2: Insert needle Hold the syringe body and firmly insert the hub of the needle (provided in the JUVÉDERM® package) into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle by turning it firmly in a clockwise direction (see Figure B) until it is seated in the proper position as shown in Figure C.
NOTE: If the position of the needle cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle cap in the other. Without twisting, pull in opposite directions to remove the needle cap as shown in Figure E.
Pre-Treatment Guidlines
What happens in the office before the injection?
Note that each doctor may have a unique process for assessing and treating patients. The following is an example of what you would likely experience with a typical procedure. Before the injection procedure your doctor will ask you questions about your medical history, as well as your treatment goals. Your doctor will discuss whether JUVÉDERM® Ultra XC is right for you and review what to expect during and after treatment, including possible side effects.
Your doctor will also examine your skin and/or lips in and around the treatment area, and may take photos. Different options for pain management will be discussed, and, if pretreatment numbing is desired, a topical such as lidocaine cream or other anesthetic agent may be used. The treatment area will be cleaned and then prepared with alcohol or other antiseptic. Your doctor may use a pen to mark your face, identifying the planned areas of injection.
Treatment Procedures
What happens during the procedure?
After the first injection, your doctor will wait a few seconds to allow the lidocaine to take effect before moving forward with the rest of the treatment. JUVÉDERM® Ultra XC will be injected in small amounts into the treatment area until the desired aesthetic outcome is achieved. Your doctor may massage the treatment area gently to assure that the product is evenly distributed. Ice may be applied for a brief period following treatment to minimize swelling and reduce pain.
Do the injections hurt?
Injections may cause some discomfort during and after the procedure. JUVÉDERM® Ultra XC contains lidocaine to reduce injection-site pain. Your doctor may also choose to numb (anesthetize) the treatment area with a topical or injected numbing agent to further minimize discomfort.
10. AFTER PROCEDURE INFORMATION
What should I expect following the procedure?
In the JUVÉDERM® Ultra XC clinical trial, the most common side effects were temporary reactions at the treatment site such as tenderness, swelling, firmness, lumps/bumps, and bruising. These side effects usually lasted 14 days or less. See Section 7 for additional information on side effects seen in the clinical study. Your doctor will also tell you what to expect following treatment with JUVÉDERM® Ultra XC. Within the first 24 hours, you should minimize strenuous exercise and exposure to extensive sun or heat. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
Injection Technique
1. JUVÉDERM® Ultra XC injectable gel is a highly cross-linked smooth gel formulation that can be injected using a fine gauge (e.g., 30-G) needle for more versatility in contouring and volumizing of facial wrinkles and folds and lips.
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touchup” implantations may be required to achieve and maintain maximum correction.
3. The patient’s soft-tissue deficiencies should be characterized with regard to etiology, distensibility, stress at the site, and depth of lesion. Depending on the type of skin, best results are obtained when the defect is readily distensible and correction can be visualized by manual manipulation (stretching) of the skin. Pretreatment photographs are recommended.
4. Although study results showed JUVÉDERM® Ultra XC to be less painful than JUVÉDERM® Ultra, supplementary anesthesia may be used for additional pain management during and after injection.
5. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be swabbed with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product flows out of the needle.
6. After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
7. The injection technique for wrinkles, folds, and lips may vary with regard to the angle and orientation of the bevel, the depth of injection, and the quantity administered. A linear threading technique, serial puncture injections, fanning technique, cross-hatching technique, or a combination have been used to achieve optimal results. Injecting the product too superficially may result in visible lumps and/or discoloration.
8. Inject JUVÉDERM® Ultra XC by applying even pressure on the plunger rod while slowly pulling the needle backwards. It is important that the injection be stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too superficially in the skin.
9. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle.
10. The typical total volume to achieve optimal correction of moderate to severe nasolabial folds is 1.6 mL per treatment site. The typical volume to achieve optimal correction for repeat treatment is 0.7 mL per treatment site.
11. The typical volume injected into the lips and perioral area to achieve optimal correction for lip augmentation is approximately 2.2 mL, which may vary depending on the goals the patient wishes to achieve. Injection volumes into the lips and perioral area after repeat treatment tended to be lower, with the typical total injection volume to achieve optimal correction being approximately 1.5 mL.
12. Correct to 100% of the desired volume effect. Do not overcorrect. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection technique. Markedly indurated defects may be difficult to correct.
13. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
14. When injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If overcorrection occurs, massage the area between your fingers or against an underlying superficial bone to obtain optimal results.
15. With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of
treatment. In these cases, it is better to invite the patient to a touch-up session after 1-2 weeks.
16. Patients may have mild to moderate injection site responses, which typically resolve in a few days in the NLFs, and within 2 weeks in the lips and perioral area. If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period.
17. After the initial treatment, an additional treatment (from 1 to 4 weeks later) may be necessary to achieve the desired level of correction. If further treatment is needed, the same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as treatment goals, wrinkle severity, lip fullness, skin elasticity, and dermal thickness at the treatment site.
18. The health care professional should instruct the patient to promptly report to her/him any evidence of problems possibly associated with the use of JUVÉDERM® Ultra XC.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® Ultra XC injectable gel is a colorless hyaluronic acid gel that contains a small quantity of local anesthetic (lidocaine) and is injected into facial tissue to smooth wrinkles and folds, especially around the nose and mouth. Hyaluronic acid is a naturally occurring sugar found in the human body. The role of hyaluronic acid in the skin is to deliver nutrients, hydrate the skin by holding in water, and to act as a cushioning agent. The role of lidocaine is to reduce the pain associated with injections into the skin.
What does it do?
JUVÉDERM® Ultra XC temporarily adds volume to facial tissue and restores a smoother appearance to the face. The lidocaine in the gel improves the comfort of the injection.
How is it used?
JUVÉDERM® Ultra XC is injected into areas of facial tissue where moderate to severe facial wrinkles and folds occur. It temporarily adds volume to the skin and may give the appearance of a smoother surface.
What will it accomplish?
JUVÉDERM® Ultra XC injectable gel will help to smooth moderate to severe facial wrinkles and folds. Most patients need 1 treatment to achieve optimal wrinkle smoothing, and the results last about 9 months to 1 year.
What are possible side effects?
Most side effects are mild or moderate in nature, and their duration is short lasting (7 days or less). The most common side effects include, but are not limited to, temporary injection-site responses such as: redness, pain/tenderness, firmness, swelling, lumps/bumps, bruising, itching, and discoloration.
As with all skin injection procedures, there is a risk of infection. One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
Are there any reasons why I should not receive JUVÉDERM® Ultra XC?
Your physician will ask about your medical history to determine if you are an appropriate candidate for treatment. The product should not be used in patients who have:
• Severe allergies marked by a history of anaphylaxis or history or presence of multiple
severe allergies
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
• Minimize strenuous exercise and exposure to extensive sun or heat within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
• Tell your doctor if you are using any medication that can prolong bleeding, such as aspirin, ibuprofen or other blood thinners. As with any injection, this may increase bruising or bleeding at the injection site.
• Tell your doctor if you are planning laser treatment, chemical peeling or any other procedure after treatment with JUVÉDERM® Ultra XC. There is a possible risk of an inflammatory reaction at the treatment site.
• Tell your doctor if you are on therapy used to decrease the body’s immune response. Use may result in an increased risk of infection.
• Tell your doctor if you are pregnant or breastfeeding. The safety for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been studied.
• Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® Ultra XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
• Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® Ultra XC in patients with a history pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
Troubleshooting
When should I notify my physician?
Call your doctor immediately if you have:
1) Changes in your vision,
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion),
3) White appearance of the skin, or
4) Unusual pain during or shortly after treatment. Be sure to also call your doctor if you have:
1) Any significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment
4) Any other symptoms that cause you concern
You may also contact the Allergan Product Support line at 1-877-345 5372.
For further questions and information, please call Allergan at 1-800 766-0171.
Administration
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Post Marketing Surveillance
The following adverse events were received from postmarket surveillance for JUVÉDERM® Ultra and Ultra Plus, with and without lidocaine, with a frequency of 5 events or more and were not observed in the clinical study; this includes reports received globally from all sources including scientific journals and voluntary reports.
All adverse events obtained through postmarket surveillance are listed in order of number of reports received: edema, lack or loss of correction, inflammatory reaction, non-inflammatory nodule, hematoma, pain, unsatisfactory result, allergic reaction, vascular occlusion, skin discoloration, device migration, neurological symptoms such as increase or decrease in sensation, infection, blister, inflammatory nodule/granuloma, dermatitis, anxiety, dry skin, overcorrection, necrosis, bleeding, herpes, headache, flu-like symptoms, varied injuries, angioedema, scarring, abscess, vision abnormalities, acne, drainage, malaise, dizziness, dyspnea, cyst, extrusion, nausea, cardiac complications, syncope, depression, telangiectasia, traumatic injury, calcification, autoimmune disorder exacerbation, beading, deeper wrinkle, and vision loss.
In many cases, the symptoms resolved without any treatment. Reported treatments have included: antibiotics, steroids, steroidal creams, hyaluronidase, anti-inflammatories, anti-histamines, needle aspiration and drainage, ultrasound therapy, analgesics, anti-viral, excision, eye drops, hyperbaric oxygen, laser resurfacing, tissue debridement, surgical scar revision, ice, massage, warm compress, anticholinergics, vasodilators, arnica, petroleum jelly, anxiolytics, antifungals, anticoagulants, and epinephrine. Vascular occlusion of vessels resulting in necrosis and vision abnormalities have been reported following injection of JUVÉDERM® products, with and without lidocaine, with a time to onset ranging from immediate to within one week following injection. These reported events likely resulted from inadvertent arterial injection. In many of these cases, the product was injected into the highly vascularized areas of the glabella, nose, and periorbital area, which are outside the device indications for use (see WARNINGS section).
Reported treatments include: anticoagulants, epinephrine, aspirin, hyaluronidase, steroid treatment, eye drops, hyperbaric oxygen, surgery, vasodilators, and warm compress. Outcomes have ranged from completely resolved to ongoing at the time of last contact. Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Adverse reactions should be reported to Allergan® Product Surveillance Department at 1-877-345-5372.
Post-treatment Checklist
What should I expect following the procedure?
In the JUVÉDERM® Ultra XC clinical trial, the most common side effects were temporary reactions at the treatment site such as tenderness, swelling, firmness, lumps/bumps, and bruising. These side effects usually lasted 14 days or less. See Section 7 for additional information on side effects seen in the clinical study. Your doctor will also tell you what to expect following treatment with JUVÉDERM® Ultra XC. Within the first 24 hours, you should minimize strenuous exercise and exposure to extensive sun or heat. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
Will I need more than one treatment to achieve my desired result?
You should discuss your treatment goals and plan with your doctor. In the JUVÉDERM® Ultra XC clinical study, 44% of subjects received a touch-up treatment 2 weeks to 1 month after initial treatment in order to achieve the desired result.
Do the results last forever?
No. While individual results may vary, in the clinical study, the results lasted for 1 year in a majority of subjects treated with JUVÉDERM® Ul
User Assistance Information
If you believe that you have experienced a serious problem related to JUVÉDERM® Ultra XC injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
What should I do if I have additional questions? For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Ultra Plus XC
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® Ultra Plus XC is a sterile, biodegradable, nonpyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of cross-linked hyaluronic acid (HA) produced by Streptococcus species of bacteria, formulated to a concentration of 24 mg/mL and 0.3% w/w lidocaine in a physiologic buffer.
Indication
JUVÉDERM® Ultra Plus XC injectable gel is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
How Supplied
JUVÉDERM® Ultra Plus XC injectable gel is supplied in individual treatment syringes with 27-G needles for single-patient use and ready for injection (implantation). The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged.
Contraindications
- JUVÉDERM® Ultra Plus XC is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® Ultra Plus XC contains trace amounts of Gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® Ultra Plus XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
The product must not be injected into blood vessels. Introduction of JUVÉDERM® Ultra Plus XC into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue llers; for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue llers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur (see Health Care Professional Instructions #11).
- Product use at specific sites in which an active in ammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection procedure reactions consist mainly of short-term in ammatory symptoms starting early after treatment and lasting ≤ 7 days’ duration. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® Ultra Plus XC is packaged for single-patient use.Do not resterilize. Do not use if package is opened or damaged.
- In order to minimize the risks of potential complications, thisproduct should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection
- Health care professionals are encouraged to discuss all potential risks of soft-tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness for the treatment of anatomic regions other than facial wrinkles and folds (eg, lips) have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® Ultra Plus XC is to be used as supplied. Modi cation or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity and performance of the product and it can therefore no longer be assured.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 18 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring and pigmentation disorders has not been studied.
- JUVÉDERM® Ultra Plus XC should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-in ammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® Ultra Plus XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan® Product Support at 1-877-345-5372.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® Ultra Plus XC, there is a possible risk of eliciting an in ammatory reaction at the implant site. An in ammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection
Adverse Experiences
A 2-week, randomized, controlled US clinical study for JUVÉDERM® Ultra XC and Ultra Plus XC compared with JUVÉDERM® Ultra and Ultra Plus without lidocaine showed a similar safety pro le in all subjects (N = 72), with the exception of fewer reports of pain/ tenderness with the product containing lidocaine. Common treatment site responses (CTR) by severity and duration, are presented in Tables 1 and 2. Aside from injection site responses, there were no adverse events related to the device, procedure, or anesthesia.
• The most common injection site responses for JUVÉDERM® Ultra Plus XC were redness, swelling, tenderness, rmness, lumps/bumps, discoloration, and bruising.
Table 1. Injection Site Responses by Maximum Severity (Number/% of Subject Nasolabial Folds [NLFs]) Injection Site Responses TOTALS JUVÉDERM® Ultra Plus XC (Na = 36 NLFs) JUVÉDERM® Ultra Plus (Na = 36 NLFs) JUVÉDERM® Ultra Plus XC nc % JUVÉDERM® Ultra Plus nc % Mild nc % Modb nc % Severe nc % Mild nc % Modb nc % Severe nc % Redness 27 75% 26 72% 19 53% 7 19% 1 3% 18 50% 8 22% 0 0% Pain 17 47% 24 67% 11 31% 6 17% 0 0% 15 42% 5 14% 4 11% Tenderness 29 81% 31 86% 24 67% 4 11% 1 3% 21 58% 7 19% 3 8% Firmness 31 86% 34 94% 21 58% 7 19% 3 8% 21 58% 10 28% 3 8% Swelling 29 81% 31 86% 19 53% 10 28% 0 0% 21 58% 9 25% 1 3% Lumps/Bumps 27 75% 27 75% 17 47% 9 25% 1 3% 15 42% 11 31% 1 3% Bruising 28 78% 28 78% 18 50% 6 17% 4 11% 16 44% 11 31% 1 3% Itching 9 25% 11 31% 9 25% 0 0% 0 0% 11 31% 0 0% 0 0% Discoloration 28 78% 23 64% 20 56% 5 14% 3 8% 12 33% 11 31% 0 0% a Number of subject NLFs treated with the respective device b Mod = Moderate c Number of NLFs with any occurrence of a particular CTR (or severity for the overall percentages) Table 2. Duration of Injection Site Responses (Number/% of Subject NLFs) Injection Site Responses JUVÉDERM® Ultra Plus XC (Na = 36 NLFs) nb % JUVÉDERM® Ultra Plus (Na = 36 NLFs) nb % Durationc 1-3 Days 4-7 Days 8-14 Days > 14 Days 1-3 Days 4-7 Days 8-14 Days > 14 Days Redness 17 47% 5 14% 3 8% 2 6% 17 47% 5 14% 2 6% 2 6% Pain 16 44% 1 3% 0 0% 0 0% 24 67% 0 0% 0 0% 0 0% Tenderness 18 50% 8 22% 3 8% 0 0% 19 53% 8 22% 3 8% 1 3% Firmness 9 25% 12 33% 6 17% 4 11% 15 42% 11 31% 3 8% 5 14% Swelling 17 47% 7 19% 4 11% 1 3% 21 58% 7 19% 1 3% 2 6% Lumps/Bumps 10 28% 8 22% 2 6% 7 19% 12 33% 6 17% 1 3% 8 22% Bruising 9 25% 7 19% 9 25% 3 8% 12 33% 11 31% 3 8% 2 6% Itching 8 22% 1 3% 0 0% 0 0% 11 31% 0 0% 0 0% 0 0% Discoloration 16 44% 5 14% 2 6% 5 14% 12 33% 5 14% 2 6% 4 11% a
Number of subject NLFs treated with the respective device b Number of subject NLFs with each specifi c injection site response by maximum duration c Duration refers to number of days from symptom onset until resolution, irrespective of date of implantation
B. Clinical Evaluation of JUVÉDERM® Ultra Plus (Without Lidocaine) In the initial randomized, controlled clinical trial to evaluate safety and effectiveness, 144 subjects were injected with JUVÉDERM® Ultra Plus in one NLF and ZYPLAST® dermal ller in the contralateral NLF. Preprinted diary forms were used by subjects to record speci c signs and symptoms experienced during each of the rst 14 days (day 0 through day 13) after initial and touchup treatments. Subjects were instructed to rate each common treatment response listed on the diary as “Mild,” “Moderate,” “Severe,” or “None.” Injection site responses reported by > 5% of subjects in either treatment group are summarized in Tables 3 and 4.
Clinical Trials
https://pubmed.ncbi.nlm.nih.gov/?term=juvederm+ultra+plus+xc&filter=pubt.clinicaltrial
Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe as shown in Figure A. Figure A
STEP 2: Insert needle Hold the syringe body and rmly insert the hub of the needle (provided in the JUVÉDERM® package) into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle by turning it rmly in a clockwise direction (see Figure B) until it is seated in the proper position as shown in Figure C.
NOTE: If the position of the needle cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position. Figure C Figure D
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle cap in the other. Without twisting, pull in opposite directions to remove the needle cap as shown in Figure E.
Pre-Treatment Guidlines
-
Treatment Procedures
It is recommended that the following information be shared with patients:
- Within the rst 24 hours, patients should avoid strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites.
- To report an adverse reaction, phone the Allergan® Product Support Department, 1-877-345-5372.
Injection Technique
1. JUVÉDERM® Ultra Plus XC injectable gel is a more highly cross-linked robust formulation, injected using a 27-G needle for volumizing and correction of deeper folds and wrinkles. Prior to treatment, the patient’s medical history should be obtained and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touchup” implantations may be required to achieve and maintain maximum correction.
2. The patient’s soft-tissue de ciencies should be characterized with regard to etiology, distensibility, stress at the site, and depth of lesion. Depending on the type of skin, best results are obtained when the defect is readily distensible and correction can be visualized by manual manipulation (stretching) of the skin. Pretreatment photographs are recommended.
3. Although the study showed JUVÉDERM® Ultra Plus XC to be less painful than JUVÉDERM® Ultra Plus, supplementary anesthesia may be used for additional pain management during and after injection.
4. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be swabbed with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product ows out of the needle.
5. After the rst small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
6. The injection technique may vary with regard to the angle and orientation of the bevel, the depth of injection, and the quantity administered. A linear threading technique, serial puncture injections, or a combination of the 2 have been used to achieve optimal results. Injecting the product too super cially may result in visible lumps and/or discoloration.
7. Inject JUVÉDERM® Ultra Plus XC applying even pressure on the plunger rod while slowly pulling the needle backward.
The wrinkle should be lifted and eliminated by the end of the injection. It is important that the injection be stopped just before the needle is pulled out of the skin to prevent material from leaking out or ending up too super cially in the skin.
8. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle.
9. The typical total volume to achieve optimal correction of moderate to severe facial wrinkles and nasolabial folds is 1.6 mL per treatment site. The typical volume to achieve optimal correction for repeat treatment is 0.7 mL per treatment site.
10. Correct to 100% of the desired volume effect. Do not overcorrect. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue and the injection technique. Markedly indurated defects may be dif cult to correct.
11. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
12. When injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If overcorrection occurs, massage the area between your ngers or against an underlying super scial bone to obtain optimal results.
13. With patients who have localized swelling, the degree of correction is sometimes difiicult to judge at the time of treatment. In these cases, it is better to invite the patient to a touch-up session after 1-2 weeks.
14. Patients may have mild to moderate injection site responses, which typically resolve in a few days. If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period.
15. After the initial treatment, an additional treatment (from 1 to 2 weeks later) may be necessary to achieve the desired level of correction. If the wrinkle needs further treatment, the same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as wrinkle severity, skin elasticity, and dermal thickness at the treatment site.
16. The health care professional should instruct the patient to promptly report to her/him any evidence of problems possibly associated with the use of JUVÉDERM® Ultra Plus XC.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® Ultra Plus XC injectable gel is a colorless hyaluronic acid gel that contains a small quantity of local anesthetic (lidocaine) and is injected into facial tissue to smooth wrinkles and folds, especially around the nose and mouth. Hyaluronic acid is a naturally occurring sugar found in the human body. The role of hyaluronic acid in the skin is to deliver nutrients, hydrate the skin by holding in water, and to act as a cushioning agent. The role of lidocaine is to reduce the pain associated with injections into the skin.
What does it do?
JUVÉDERM® Ultra Plus XC temporarily adds volume to facial tissue and restores a smoother appearance to the face. The lidocaine in the gel improves the comfort of the injection. How is it used? JUVÉDERM® Ultra Plus XC is injected into areas of facial tissue where moderate to severe facial wrinkles and folds occur. It temporarily adds volume to the skin and may give the appearance of a smoother surface.
What will it accomplish?
JUVÉDERM® Ultra Plus XC injectable gel will help to smooth moderate to severe facial wrinkles and folds. Most patients need 1 treatment to achieve optimal wrinkle smoothing, and the results last about 1 year. What are possible side effects? Most side effects are mild or moderate in nature, and their duration is short lasting (7 days or less). The most common side effects include, but are not limited to, temporary injection-site responses such as: redness, pain/tenderness, firmness, swelling, lumps/bumps, bruising, itching, and discoloration. As with all skin injection procedures, there is a risk of infection. One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
Are there any reasons why I should not receive JUVÉDERM® Ultra Plus XC (contraindications)? Your physician will ask about your medical history to determine if you are an appropriate candidate for treatment. The product should not be used in patients who have:
- Severe allergies marked by a history of anaphylaxis or history or presence of multiple severe allergies
- A history of allergies to lidocaine or Gram-positive bacterial proteins
Safety
The following are important treatment considerations for you to discuss with your physician and understand in order to help avoid unsatisfactory results and complications.
- Patients who are using substances that can prolong bleeding, such as aspirin or ibuprofen, as with any injection, may experience increased bruising or bleeding at injection site. You should inform your physician before treatment if you are using these types of substances
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® Ultra Plus XC, there is a possible risk of an inflammatory reaction at the treatment site
- JUVÉDERM® Ultra Plus XC injectable gel should be used with caution in patients on immunosuppressive therapy, or therapy used to decrease the body’s immune response, as there may be an increased risk of infection
- The safety for use during pregnancy, in breast-feeding females, or in patients under 18 years has not been established
- The safety in patients with a history of excessive scarring (eg, hypertrophic scarring and keloid formations) and pigmentation disorders has not been studied
Troubleshooting
Call your doctor immediately if you have:
1) Changes in your vision,
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion),
3) White appearance of the skin, or 4) Unusual pain during or shortly after treatment Be sure to also call your doctor if you have:
1) Any significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment
4) Any other symptoms that cause you concern.
You may also contact the Allergan Product Support line at 1-877-345-5372. For further questions and information, please call Allergan at 1-800-766-0171.
Administration
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Post Marketing Surveillance
The following adverse events were received from postmarket surveillance for JUVÉDERM Ultra and Ultra Plus, with and without lidocaine, which were not observed in the clinical trials; this includes reports received globally from all sources including scientific journals and voluntary reports. All adverse events obtained through postmarket surveillance with a frequency of 5 or more events are listed in order of prevalence: edema, inflammatory reaction, noninflammatory nodule, lack or loss of correction, pain, hematoma, unsatisfactory result, allergic reaction, skin discoloration, vascular occlusion, device migration, infection, neurological symptoms such as increase or decrease in sensation, inflammatory nodule/ granuloma, dermatitis, blister, dry skin, anxiety, overcorrection, necrosis, bleeding, abscess, herpes, u-like symptoms, scarring, varied injuries, angioedema, vision abnormalities, acne, headache, malaise, drainage, dyspnea, extrusion, cyst, dizziness, syncope, telangiectasia, anaphylactic reaction, calcification, depression, nausea, autoimmune disorder exacerbation, beading, deeper wrinkle, cardiac complications, vision loss, and traumatic injury.
In many cases, the symptoms resolved without any treatment.
Reported treatments have included: antibiotics, steroids, steroidal creams, hyaluronidase, anti-inflammatories, anti-histamines, needle aspiration and drainage, ultrasound therapy, analgesics,
anti-viral, excision, eye drops, hyperbaric oxygen, laser resurfacing,
tissue debridement, surgical scar revision, ice, massage, warm compress, anticholinergics, vasodilators, arnica, petroleum jelly, anxiolytics, antifungals, anticoagulants, and epinephrine. In ammatory reaction at the injection site, mostly a nonserious event, has been reported in association with edema, erythema, ecchymosis, pruritus, induration, pain, nodule, blister, abscess, and infection. Time to onset ranged from 1 day to 4 months post JUVÉDERM® Ultra Plus injection, and outcome ranged from resolved to ongoing at last contact. Interventions prescribed by the health care professionals included topical steroidal cream, oral steroids, and antibiotics. Additional treatment noted was a needle aspiration for drainage of an abscess.
Vascular occlusion of vessels resulting in necrosis and vision abnormalities have been reported following injection of JUVÉDERM® products, with and without lidocaine, with a time to onset ranging from immediate to within 1 week following injection. These reported events likely resulted from inadvertent arterial injection. In many of these cases, the product was injected into the highly vascularized areas of the glabella, nose, and periorbital area, which are outside the device indications for use (see WARNINGS section). Reported treatments include: anticoagulants, epinephrine, aspirin, hyaluronidase, steroid treatment, eye drops, hyperbaric oxygen, surgery, vasodilators, and warm compress. Outcomes have ranged from completely resolved to ongoing at the time of last contact.
Serious adverse events have infrequently been reported for
JUVÉDERM® Ultra Plus (reported with a frequency of 5 or more).
The most commonly reported serious adverse events were edema,
erythema, ecchymosis, and pain.
• The onset of edema, erythema, and pain generally varied from immediate to 2 months post injection. The treatment prescribed included NSAIDs, anti-histamines, antibiotics, steroids, and hyaluronidase. In most cases, the reported events resolved within a few days to 5 weeks.
• The onset of ecchymosis generally varied from immediate to 1 day post injection. The treatment prescribed included NSAIDs, anti-histamines, antibiotics, steroids, and hyaluronidase. In most cases ecchymosis resolved within a few days to 6 weeks. Additionally there have been reports of nodules, infection, and inflammation.
• The onset of nodules generally varied from immediate to 2 months post injection. The treatment prescribed included NSAIDs, antibiotics, steroids, and hyaluronidase. In most cases nodules resolved within 1 month.
• The onset of infection generally varied from immediate to 1 month post injection. The treatment prescribed included antibiotics, pain killers, and antibacterial drugs.
• The onset of inflammation generally varied from the day of treatment to 1 day post injection. The treatment prescribed included antibiotics, steroids, and needle aspiration. Resolution of symptoms has been reported within 4 days. Delayed-onset inflammation near the site of dermal filller injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to the Alle
Post-treatment Checklist
A subset of subjects enrolled in a prospective, multicenter study for follow-up after repeat treatment. Subjects were eligible for the follow-up study if they completed the pivotal study, indicated that they preferred JUVÉDERM® Ultra Plus over the control device, and received repeat treatment between 24 and 36 weeks after their last treatment in the pivotal study.
Subjects underwent repeat treatment with JUVÉDERM® Ultra Plus in both NLFs. Demographics for subjects enrolled in the repeat treatment extended follow-up study were similar to those in the pivotal study. Routine follow-up visits for safety and effectiveness occurred at 4, 12, 24, 36, and 48 weeks after the repeat treatment. The Investigator evaluated each subject for signs and symptoms of serious or unanticipated adverse events. The Investigator also evaluated the severity of the subject’s NLFs using the validated 5-point (range 0 to 4) photographic NLF severity scale. The subject made independent self-assessments of NLF severity using the nonphotographic 5-point grading scale.
No serious or unanticipated adverse events were reported. The effectiveness results for repeat treatment with JUVÉDERM® Ultra Plus based on the Investigator’s assessment of NLF severity after repeat treatment are presented in Table 8.
User Assistance Information
What if I experience a problem?
If you believe that you have experienced a serious problem related to JUVÉDERM® Ultra Plus injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
What should I do if I have additional questions?
For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Voluma
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® VOLUMA™ XC is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of hyaluronic acid (HA) produced by Streptococcus species of bacteria, which is crosslinked with BDDE. It is formulated to a concentration of 20 mg/mL and 0.3% w/w lidocaine in a physiologic buffer.
Indication
JUVÉDERM® VOLUMA™ XC is indicated for deep (subcutaneous and/ or supraperiosteal) injection for cheek augmentation to correct agerelated volume deficit in the mid-face and for augmentation of the chin region to improve the chin profile in adults over the age of 21.
How Supplied
JUVÉDERM® VOLUMA™ XC injectable gel is supplied in individual treatment syringes with needles as indicated on the carton. JUVÉDERM® VOLUMA™ XC can be injected with either a 27-G, ½" needle; a 25-G, 1" needle; or a 25-G, 1½" cannula. The TSK STERiGLIDE ™ 25-G, 1½" cannula is not supplied with JUVÉDERM® VOLUMA™ XC, but is available for purchase through Allergan. The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is open or damaged.
Self Life and Storage
JUVÉDERM® VOLUMA™ XC injectable gel must be used prior to the expiration date printed on the label.
Store at room temperature (up to 25°C/77°F). DO NOT FREEZE.
JUVÉDERM® VOLUMA™ XC injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan Product Surveillance immediately at (877) 345-5372.
To place an order, contact Allergan at (800) 377-7790. 1 Alam M, Gladstone H, Kramer EM, et al. ASDS guidelines of care: injectable fillers. Dermatol Surg. 2008;34(suppl 1):S115-S148.
Contraindications
- JUVÉDERM® VOLUMA™ XC is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® VOLUMA™ XC contains trace amounts of Grampositive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® VOLUMA™ XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- The product must not be injected into blood vessels. Introduction of JUVÉDERM® VOLUMA™ XC into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers; for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur (see Health Care Professional Instructions #17).
- Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Treatment site reactions consist mainly of short-term inflammatory symptoms and generally resolve within 2 to 4 weeks. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® VOLUMA™ XC is packaged for single-patient use. Do not resterilize. Do not use if package is open or damaged.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies and a toxicological risk assessment, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness for the treatment of anatomic regions other than the mid-face, chin, and pre-jowl sulcus regions have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® VOLUMA™ XC is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, and in patients with very thin skin in the mid-face region has not been established.
- The safety has been established for use in patients between 35 and 65 years of age for cheek augmentation and patients between 22 and 80 years of age for chin augmentation.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- JUVÉDERM® VOLUMA™ XC should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at treatment sites.
- Patients who experience skin injury near the site of JUVÉDERM® VOLUMA™ XC implantation may be at a higher risk for adverse events.
- Patients may experience late onset nodules with use of dermal fillers, including JUVÉDERM® VOLUMA™ XC. Refer to ADVERSE EVENTS section for details.
- The safety and effectiveness of cannula injection of JUVÉDERM® VOLUMA™ XC has only been clinically evaluated with the TSK STERiGLIDE ™ 25-G, 1½" cannula.
- The safety of JUVÉDERM® VOLUMA™ XC with cannula for cheek augmentation has not been established in patients with Fitzpatrick Skin Types V and VI.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® VOLUMA™ XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan Product Surveillance at (877) 345-5372.
- JUVÉDERM® VOLUMA™ XC should only be used by health care professionals who have appropriate experience and who are knowledgeable about the anatomy and the product for use in deep (subcutaneous and/or supraperiosteal) injection for cheek and chin augmentation.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
- Skin laxity of the chin, neck, or jaw could obscure the effects of JUVÉDERM® VOLUMA™ XC treatment in the chin region. Therefore, in the chin study, the device was not evaluated in subjects with significant skin laxity of the chin, neck, or jaw.
- The effect of JUVÉDERM® VOLUMA™ XC injection into the chinon facial hair growth has not been studied.
Adverse Experiences
A. Clinical Evaluation of JUVÉDERM® VOLUMA™ XC for Cheek Augmentation In the randomized, controlled clinical trial to evaluate the safety and effectiveness of JUVÉDERM® VOLUMA™ XC, there were 238 subjects treated with JUVÉDERM® VOLUMA™ XC in the mid-face (zygomaticomalar region, anteromedial cheek, and/or submalar region, see Figure 1) during the primary phase of the study. Touchup treatments occurred approximately 30 days after initial injection. After the 6-month blinded “no treatment” control period, control subjects were allowed to receive treatment; 32 control subjects were treated in the study. Preprinted diary forms were used by subjects after treatment to record specific signs and symptoms experienced during each of the first 30 days after initial, touch-up, and repeat treatments in each region of the mid-face. Of the 270 subjects who underwent treatment (from both the treatment and control groups), 265 completed the diary forms. A subset of subjects also underwent repeat treatment following completion of the extended follow-up phase of the study, with 162 subjects completing diary forms after repeat treatment. Subjects were instructed to rate each treatment site response listed on the diary as “Mild (barely noticeable),” “Moderate (uncomfortable),” “Severe (severe discomfort),” or “None.”
After initial treatment with JUVÉDERM® VOLUMA™ XC, 98% of subjects reported experiencing a local treatment site response. Subjects rated treatment site responses as predominantly mild (21.5%) or moderate (59.2%) in severity with a duration of 2 to 4 weeks. For those treatment site responses evaluated as moderate or severe, the median duration as moderate or severe was 2 days, and the median time to complete resolution was 6 days. Based on data from 167 subjects who received repeat treatment, treatment site responses following repeat treatment were less severe, with reduced incidence and duration compared to initial treatment. Treatment site responses reported by > 5% of subjects after initial treatments are summarized by severity in Table 1 and by duration in Table 2.
a Maximum severity reported in the diary. The denominator for percentages by severity is the number of subjects with the corresponding treatment site response.
b N denotes number of subjects who recorded responses in the diaries after the initial treatment.
Treatment site responses reported by ≤ 5% of subjects included ache, acne, bulge, bumps, cheek larger upon waking up, dry patch, fine wrinkles, injection/needle marks, numbness, pigmentation from treatment, puffiness, rash, scratch near injection point, soreness, tightness, and yellowness.
Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe, as shown in.
STEP 2: Insert needle Hold the syringe body and firmly insert the hub of the needle (provided in the JUVÉDERM® VOLUMA™ XC package) into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle by turning it firmly in a clockwise direction (see Figure B) until it is seated in the proper position, as shown in
NOTE: If the position of the needle cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle cap in the other. Without twisting, pull in opposite directions to remove the needle cap, as shown in Figure E
Pre-Treatment Guidlines
4. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
Treatment Procedures
It is recommended that the following information be shared with patients:
- Within the first 24 hours, patients should avoid strenuous exercise and extensive sun or heat exposure. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the treatment sites
- If the treated area is swollen, an ice pack may be applied to the site for a short period
- To report an adverse reaction, phone the Allergan Product Surveillance Department at (877) 345-5372
Injection Technique
1. JUVÉDERM® VOLUMA™ XC injectable gel is a crosslinked, robust, injectable gel formulation, injected using a 27-G, ½" or 25-G, 1" needle; or a 25-G, 1½" cannula to volumize and contour the cheek for correction of mid-face volume deficit and to augment the chin region to improve the chin profile.
2. The TSK STERiGLIDE ™ 25-G, 1½" cannula was used in the clinical trials (cannula study for cheek and chin study) and is recommended for use with JUVÉDERM® VOLUMA™ XC. An entry point was made in the skin with the TSK 23-G introducer needle. In the chin clinical study, JUVÉDERM® VOLUMA™ XC was injected into the pogonion (needle), menton (needle or cannula), and left and right pre-jowl sulci (needle or cannula).
3. JUVÉDERM® VOLUMA™ XC with needle was studied in all Fitzpatrick Skin Types for deep (subcutaneous and/or supraperiosteal) injection for cheek augmentation to correct age-related volume deficit in the mid-face in adults over the age of 21. However, the safety of JUVÉDERM® VOLUMA™ XC with cannula for cheek augmentation has not been established in Fitzpatrick Skin Types V and VI.
4. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
5. The patient’s soft-tissue deficiencies should be characterized with regard to etiology, distensibility, stress at the site, and depth of lesion. Pre-treatment photographs are recommended.
6. Topical or injectable anesthesia may be used to manage pain during and after injection.
7. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product flows out of the needle/cannula.
8. If the needle/cannula is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle/cannula.
9. When using a cannula, an entry point is made in the skin; eg, with a sharp needle of appropriate size.
10. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not intravascular.
11. After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
12. The injection technique for JUVÉDERM® VOLUMA™ XC with regard to the angle and orientation of the bevel, the depth (subcutaneous and/or submuscular/supraperiosteal) of injection, and the quantity administered may vary depending on the area being treated. Injection of JUVÉDERM® VOLUMA™ XC too superficially (intradermally), or in large volumes over a small area, may result in visible and persistent lumps and/or discoloration.
13. Tunneling, fanning, crosshatching, and ferning techniques may be used with a needle or cannula to deliver JUVÉDERM® VOLUMA™ XC to achieve optimal results. Serial puncture may be used with a needle to deliver JUVÉDERM® VOLUMA™ XC to achieve optimal results. Bolus and serial puncture techniques may be used to achieve optimal results in the chin area. Injection may be administered in an antegrade or retrograde fashion. Inject JUVÉDERM® VOLUMA™ XC while applying even pressure on the plunger rod and slowly moving the needle/cannula in the subcutaneous or submuscular/supraperiosteal plane.
14. JUVÉDERM® VOLUMA™ XC should be distributed in small aliquots (small boluses of 0.1 mL to 0.2 mL) over a large area to reduce the risk of persistent lumpiness.
15. With submuscular/supraperiosteal injection, the number of times the needle passes through the muscle should be minimized to reduce the risk of bruising. It is important to stop injecting before the needle tip reaches the level of the deep dermis to prevent material from being placed too superficially in the skin.
16. Correct to 100% of the desired volume effect. Do not overcorrect. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection technique. Markedly indurated defects may be difficult to correct.
17. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
18. The area of lost facial volume should be lifted by the end of the injection. When injection is completed, the treated site may be gently massaged to mold the product to the contour of the surrounding tissue and assure that it is evenly distributed and conforms to the contour of the surrounding tissues. If overcorrection occurs, massage the area between your fingers or against an underlying superficial bone to obtain optimal results.
19. With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of treatment. In these cases, it is better to invite the patient back to the office for a touch-up treatment.
20. After the initial treatment, an additional treatment may be necessary to achieve the desired level of correction. The same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as mid-face volume deficit or chin retrusion severity, skin elasticity, and dermal thickness at the treatment site.
21. Patients may experience treatment site responses, which typically resolve within 2 to 4 weeks for treatment in the cheek and the chin. Ice may be applied for a brief period following treatment to minimize swelling and reduce pain.
22. The health care professional should instruct the patient to promptly report any evidence of problems possibly associated with the use of JUVÉDERM® VOLUMA™ XC
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® VOLUMA™ XC injectable gel is a smooth, colorless hyaluronic acid (HA) gel that contains a small quantity of local anesthetic (lidocaine). HA is a naturally occurring sugar found in the human body. The role of HA in the skin is to deliver nutrients and help the skin retain its natural moisture and softness. The addition of lidocaine helps to improve the comfort of the injection. JUVÉDERM® VOLUMA™ XC injectable gel is manufactured using VYCROSS® technology; during which, a small amount of the biodegradable compound BDDE is added to crosslink the HA in the gel. VYCROSS® technology results in a specialized smooth-gel filler that produces long-lasting results at the treatment site. JUVÉDERM® VOLUMA™ XC is delivered by an injection into the chin and surrounding area of the face for shaping of the chin. 3. INDICATION/INTENDED USE
What is it for?
JUVÉDERM® VOLUMA™ XC is indicated for deep (subcutaneous and/or supraperiosteal) injection for augmentation of the chin region to improve the chin profile in adults over the age of 21.
What does it do?
JUVÉDERM® VOLUMA™ XC injectable gel is injected into the chin area to increase the chin projection. It temporarily adds volume to the chin area and results in an improved chin shape. Figure 1 shows the treatment areas for JUVÉDERM® VOLUMA™ XC for chin augmentation. Figure 1. Treatment Area for JUVÉDERM® VOLUMA™ XC for Chin Augmentation
How is it used?
It is injected under the skin, just above the bone, into the chin area using a small needle or cannula (blunt tip needle).
Are there any reasons why I should not receive JUVÉDERM® VOLUMA™ XC injectable gel?
Your doctor will ask about your medical history to determine if you are an appropriate candidate for treatment.
• You should not use the product if you have severe allergies with a history of severe reactions (anaphylaxis) or history or presence of multiple severe allergies. Use may result in an allergic reaction.
• You should not use the product if you are allergic to lidocaine or to the proteins used to make the HA in JUVÉDERM® VOLUMA™ XC (Gram-positive bacterial proteins). Use may result in an allergic reaction.
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
• Minimize strenuous exercise and exposure to extensive sun or heat within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
• Tell your doctor if you are pregnant or breastfeeding. The safety of JUVÉDERM® VOLUMA™ XC injectable gel for use during pregnancy, or in women who are breastfeeding, has not been studied.
• Tell your doctor your age and discuss how your age may influence your decision to use this product. The safety of JUVÉDERM® VOLUMA™ XC has not been studied in patients under 22 years or over 80 years.
• Tell your doctor which areas of your face you would like to have treated. This product is intended for use in the chin and cheek (refer to the JUVÉDERM® VOLUMA™ XC Patient Label for Cheek Augmentation) areas. The safety and effectiveness for treatment in other areas have not been established in controlled clinical studies.
• Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® VOLUMA™ XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
• Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® VOLUMA™ XC in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
• Tell your doctor if you are on therapy used to decrease the body’s immune response (immunosuppressive therapy). Use may result in an increased risk of infection.
• Tell your doctor before treatment if you are using substances that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may result in increased bruising or bleeding at the injection site.
• Patients who experience skin injury near the site of JUVÉDERM® VOLUMA™ XC implantation may be at a higher risk for adverse events.
• Loose skin of the chin, neck, or jaw could obscure the effects of JUVÉDERM® VOLUMA™ XC treatment in the chin region. Therefore, in the chin study, the device was not evaluated in subjects with significant loose skin of the chin, neck, or jaw.
• The effect of JUVÉDERM® VOLUMA™ XC injection into the chin on facial hair growth has not been studied. 6. RISKS What are possible side effects? In the clinical study, most side effects were mild (easily tolerated) in nature, and generally resolved in 2 to 4 weeks. The most common side effects include temporary reactions at the treatment site such as tenderness, firmness, swelling, pain, lumps/ bumps, bruising, redness, itching, and discoloration. These side effects are consistent with other facial-injection procedures. See Section 14 for additional information on side effects seen in the clinical study. Although most side effects will resolve with time, some side effects may persist longer than 30 days. Your doctor may choose to treat them with medications, such as antibiotics, steroids, or hyaluronidase (an enzyme that breaks down HA). As with all skin-injection procedures, there is a risk of infection. One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications.
- Minimize strenuous exercise and exposure to extensive sun or heat within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are pregnant or breastfeeding. The safety of JUVÉDERM® VOLUMA™ XC injectable gel for use during pregnancy, or in women who are breastfeeding, has not been studied.
- Tell your doctor your age and discuss how your age may influence your decision to use this product. The safety of JUVÉDERM® VOLUMA™ XC has not been studied in patients under 35 years or over 65 years.
- Tell your doctor which areas of your face you would like to have treated. This product is intended for use in the cheek and chin (refer to the JUVÉDERM® VOLUMA™ XC Patient Label for Chin Augmentation) areas. The safety and effectiveness for treatment in other areas have not been established in controlled, clinical studies.
- Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® VOLUMA™ XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
- Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® VOLUMA™ XC in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
- Tell your doctor if you are on therapy used to decrease the body’s immune response (immunosuppressive therapy). Use may result in an increased risk of infection.
- Tell your doctor before treatment if you are using substances that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may result in increased bruising or bleeding at the injection site.
- Patients who experience skin injury near the site of JUVÉDERM® VOLUMA™ XC implantation may be at a higher risk for adverse events.
- The safety of JUVÉDERM® VOLUMA™ XC with cannula has not been established in patients with darker skin types (Fitzpatrick Skin Types V and VI).
Troubleshooting
When should I call my doctor?
Call your doctor immediately if you have:
1) Changes in your vision,
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion),
3) White appearance of skin, or
4) Unusual pain during or shortly after treatment Be sure to also call your doctor if you have:
1) Significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment
4) Any other symptoms that cause you concern
You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
Administration
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Post Marketing Surveillance
JUVÉDERM® VOLUMA™ without lidocaine has been marketed outside the US since 2005, and JUVÉDERM® VOLUMA™ XC (also known as JUVÉDERM® VOLUMA™ with lidocaine) has been marketed outside the US since 2009 and in the US since 2013.
The following AEs were received from postmarket surveillance for JUVÉDERM® VOLUMA™ XC with and without lidocaine with a frequency of 5 events or more and were not observed during the follow-up in the chin (12 months) or cheek (24 months) US pivotal clinical studies; this includes reports received globally from all sources including scientific journals and voluntary reports. All AEs obtained through postmarket surveillance are listed in order of number of reports received: edema, inflammatory reaction, noninflammatory nodule, pain, loss/lack of correction, inflammatory nodule/granuloma, unsatisfactory result, hematoma, allergic reaction, bruising, infection, skin discoloration, device migration, neurological symptoms such as increase or decrease in sensation, vascular occlusion, abscess, anxiety, dermatitis, varied injuries, headache, vision abnormalities, drainage, flu-like symptoms, blister, overcorrection, scarring, necrosis, bleeding, malaise, cyst, dry skin, acne, dizziness, herpes, autoimmune disorder exacerbation, angioedema, lymphadenopathy, syncope, nausea, dyspnea, extrusion, telangiectasia, depression, vision loss, calcification, anaphylactic reaction, cardiac complications, biofilm, and deeper wrinkle. Reported treatments include: antibiotics, steroids, antiseptic creams, hyaluronidase, anti-inflammatories, antihistamines, needle aspiration, eye drops, hyperbaric oxygen treatment, laser treatment, ice, massage, warm compress, analgesics, anti-virals, ultrasound therapy, excision, drainage, surgery, immunosuppressants, petroleum jelly, arnica, anticoagulants, anxiolytics, ACE inhibitors, and vasodilators.
Vision abnormalities have been reported following injection of JUVÉDERM® VOLUMA™, with and without lidocaine, into the nose, glabella, periorbital area, and/or cheek, with a time to onset ranging from immediate to 1 week following injection. Reported treatments include anticoagulants, sympathomimetics, steroids, and surgery. Outcomes ranged from resolved to ongoing at the time of last contact. Events requiring medical intervention, and events where resolution information is not available, were reported after injection of JUVÉDERM® VOLUMA™ with and without lidocaine in the highly vascularized areas of the glabella, nose, and periorbital area, which are outside the device indications for use (see Warnings section). Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Allergan Product Surveillance Department at (877) 345-5372.
Post-treatment Checklist
What should I expect following the procedure? In the clinical trial the most common side effects were temporary reactions at the treatment site such as tenderness, swelling, firmness, and lumps/bumps. These side effects generally lasted 2 to 4 weeks. See Section 14 for additional information on side effects seen in the clinical study. Your doctor will also tell you what to expect following treatment with JUVÉDERM® VOLUMA™ XC injectable gel. Within the first 24 hours, you should minimize strenuous exercise and exposure to extensive sun or heat. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
User Assistance Information
What if I experience a problem?
If you believe that you have experienced a serious problem related to JUVÉDERM® VOLUMA™ XC injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
What should I do if I have additional questions?
For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Volbella
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® VOLBELLA® XC injectable gel is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of cross-linked hyaluronic acid (HA) produced by Streptococcus species of bacteria, formulated to a concentration of 15 mg/mL with 0.3% w/w lidocaine in a physiologic buffer
Indication
JUVÉDERM® VOLBELLA® XC injectable gel is indicated for injection into the lips for lip augmentation and for correction of perioral rhytids in adults over the age of 21. JUVÉDERM® VOLBELLA® XC is indicated for the improvement of infraorbital hollowing in adults over the age of 21.
How Supplied
JUVÉDERM® VOLBELLA® XC injectable gel is supplied in individual treatment syringes with 30-G or 32 G needles for single-patient use and ready for injection (implantation). The TSK STERiGLIDE® 27-G 1½" cannula is not supplied with JUVÉDERM® VOLBELLA® XC but is available for purchase through Allergan. The volume in each syringe is as stated on the syringe label and the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged
Self Life and Storage
JUVÉDERM® VOLBELLA® XC injectable gel must be used prior to the expiration date printed on the label.
Store at room temperature (up to 25°C/77°F). DO NOT FREEZE.
JUVÉDERM® VOLBELLA® XC injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan Product Support immediately at 1-877-345-5372.
To place an order, contact Allergan at 1-800-377-7790.
Contraindications
- JUVÉDERM® VOLBELLA® XC is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® VOLBELLA® XC contains trace amounts of Gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® VOLBELLA® XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- The product must not be injected into blood vessels. Introduction of JUVÉDERM® VOLBELLA® XC injectable gel into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft-tissue fillers, for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly, and apply the least amount of pressure necessary. Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see Health Care Professional Instructions #19).
- Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection site responses consist mainly of short-term inflammatory symptoms starting early after treatment and lasting ≤ 30 days. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® VOLBELLA® XC injectable gel is packaged for single-patient use. Do not resterilize. Do not use if package is opened or damaged.
- In order to minimize the risks of potential complications, this product should only be used by health care professionals who have been trained in facial anatomy and vasculature, safe injection techniques, and identification and management of potential adverse events, including intravascular complications.
- Health care professionals are encouraged to discuss all potential risks of soft-tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness for the treatment of anatomic regions other than the lips, perioral area, and infraorbital hollows have not been established in controlled clinical studies. • Injection of more than 6.0 mL of JUVÉDERM® VOLBELLA® XC injectable gel for lip augmentation and correction of perioral rhytids, and more than 2.2 mL per infraorbital hollow, has not been studied.
- As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® VOLBELLA® XC injectable gel is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 22 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- JUVÉDERM® VOLBELLA® XC injectable gel should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- Patients may experience late onset adverse events with use of dermal fillers, including JUVÉDERM® VOLBELLA® XC. Refer to ADVERSE EVENTS section for details.
- After use, treatment syringes and needles are biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® VOLBELLA® XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan Product Support at 1-877-345-5372.
- JUVÉDERM® VOLBELLA® XC should only be used by health care professionals who have appropriate experience and who are knowledgeable about the anatomy and the product for use in the lips, perioral area, and infraorbital hollows.
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® VOLBELLA® XC, there is a possible risk of eliciting an inflammatory reaction at the implant site. An inflammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A. US Pivotal Study of JUVÉDERM® VOLBELLA® XC for Lip Augmentation and Perioral Rhytids In the multicenter, double-blind, randomized, controlled clinical trial to evaluate the safety and effectiveness of JUVÉDERM® VOLBELLA® XC versus Restylane-L® (control) for lip augmentation and correction of perioral rhytids, subjects were randomized and treated in a 3:1 ratio with either JUVÉDERM® VOLBELLA® XC (N = 168) or control (N = 56).
Subjects used preprinted diary forms to record specific signs and symptoms of injection site responses (ISRs) experienced during the 30 days after initial treatment, touch-up treatment (if performed), and repeat treatment. Subjects were instructed to rate each ISR listed on the diary as Mild, Moderate, Severe, or None.
• Mild ISRs were defined as awareness of sign or symptom but easily tolerated.
• Moderate ISRs were defined as discomfort enough to cause interference with usual activity.
• Severe ISRs were defined as incapacitating with inability to work or do usual activity.
The severity and duration of all ISRs reported by > 5% of subjects who completed post-treatment diary forms after initial treatment are summarized in Table 1 and Table 2, respectively. Table 3 shows the severity and duration of all ISRs after repeat treatment reported by > 5% of subjects. The majority of ISRs were mild or moderate in intensity, and their duration was short lasting (30 days or less). There were no significant differences in ISRs reported between JUVÉDERM® VOLBELLA® XC and control. The incidence, severity, and duration of ISRs reported after the touch-up and repeat treatments were generally lower than those reported after initial treatment.
Directions For Assembly
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Assembly Of Needle To Syringe
To ensure proper attachment to the syringe, use the 30-G or 32-G needle provided or the TSK STERiGLIDE® 27-G, 1½" cannula.
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe, as shown in Figure A.
STEP 2: Insert needle or cannula Hold the syringe body and firmly insert the hub of the needle (provided in the JUVÉDERM® package) or cannula (provided separately) into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle or cannula Tighten the needle or cannula by turning it firmly in a clockwise direction (see Figure B) until it is seated in the proper position, as shown in Figure C.
NOTE: If the position of the needle or cannula cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle or cannula is seated in the proper position.
STEP 4: Remove the needle or cannula cap Hold the syringe body in one hand and the needle or cannula cap in the other. Without twisting, pull in opposite directions to remove the cap, as shown in Figure E.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients should also be advised that supplemental touch-up treatments may be required to achieve and maintain maximum correction
Treatment Procedures
It is recommended that the following information be shared with patients:
- Within the first 24 hours, patients should avoid strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites.
- To report an adverse reaction, phone the Allergan Product Support Department at 1 877 345 5372.
Injection Technique
- JUVÉDERM® VOLBELLA® XC injectable gel is a highly crosslinked, soft, smooth gel formulation that can be injected using a fine-gauge needle (eg, 30-G or 32-G) into the lips and perioral area to add fullness and improve the shape of the lips, and to smooth perioral rhytids. JUVÉDERM® VOLBELLA® XC can also be injected using a fine-gauge needle (eg, 32-G) or cannula (eg, 27-G) to add volume from the lower eyelid to the anteromedial cheek for a smooth transition.
- The TSK STERiGLIDE® 27-G, 1½" cannula was used in the clinical trial and is the only cannula recommended for use with JUVÉDERM® VOLBELLA® XC.
- Educational resources are available through the Allergan Medical Institute, which provides training in facial anatomy and vasculature, effective patient assessment, safe injection techniques, and identification and management of potential adverse events, including vascular complications. Health care practitioners may contact Allergan for educational and training resources.
- Completion of device-specific use training is required and will be verified prior to purchase of JUVÉDERM® VOLBELLA® XC for the improvement of infraorbital hollows.
- Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients should also be advised that supplemental touch-up treatments may be required to achieve and maintain maximum correction.
- Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual field testing.
- Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
- Ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines1
- Identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal filler injection
- Conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system deficits
- For lip augmentation and treatment of perioral lines, the patient’s treatment goals should be characterized with regard to proper proportion of upper and lower lip, vertical height, horizontal length, vermilion fullness, contouring of the vermilion border, Cupid’s bow, and philtral columns, as well as perioral lip rhytids and oral commissures. Pretreatment photographs are recommended. For treatment of infraorbital hollowing, the patient’s treatment goals should be characterized by improving the infraorbital hollows for a natural-looking contour.
- Supplementary anesthesia may be used for additional pain management during and after injection.
- After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be swabbed with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product flows out of the needle.
- After insertion of the needle, and just before injection, retract the plunger rod to slightly aspirate and verify the needle is not intravascular. If blood is withdrawn, this could indicate intravascular placement, therefore stop immediately, reposition the needle/cannula and repeat the retraction step again. The absence of blood does not necessarily exclude intravascular placement. Therefore, it is important to inject the product slowly and apply the least amount of pressure necessary.
- After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
- The injection technique may vary with regard to angle and orientation of the needle bevel, injection depth, and the quantity administered. Tunneling, serial puncture, fanning, or a combination of these techniques may be used for lip augmentation or treatment of infraorbital hollowing to achieve optimal results. Crosshatching and bolus injection techniques have also been used to achieve optimal results for the treatment of infraorbital hollows. Injecting the product too superficially may result in visible lumps and/or discoloration.
- Inject JUVÉDERM® VOLBELLA® XC by applying slow and even pressure on the plunger rod. It is important that the injection be stopped before the needle is pulled out of the skin to prevent material from leaking out or being placed too superficially in the skin.
- If the needle or cannula is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle or cannula.
- The typical volume injected into the lips and perioral area to achieve optimal correction was approximately 2.6 mL, which may vary depending on the goals the patient wishes to achieve. Injection volumes into the lips and perioral area after repeat treatment tended to be lower, with the typical total injection volume to achieve optimal correction being approximately 1.6 mL.
- The typical volume injected in the infraorbital hollows to achieve optimal improvement was approximately 1.0 mL in each infraorbital area, which may vary depending on the goal the patient wishes to achieve. Injection volumes into the infraorbital hollows after repeat treatment tended to be lower, with the typical total injection volume to achieve optimal improvement being approximately 0.4 mL in each infraorbital area.
- Correct to 100% of the desired volume effect. Do not overcorrect. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection technique. Markedly indurated defects may be difficult to correct.
- If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
- When injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If overcorrection occurs, massage the area with your fingers or against an underlying superficial bone and/or teeth to obtain optimal results.
- With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of treatment. In these cases, it is better to invite the patient back to the office for a touch-up treatment.
- After the initial treatment, an additional touch-up treatment may be necessary to achieve the desired level of correction. If further treatment is needed, the same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as treatment goals, skin elasticity, and dermal thickness at the treatment site.
- Patients may have mild to moderate injection-site responses after treatment in the lips, perioral area, and infraorbital hollows, which typically resolve within 14 days. Ice may be applied, using gentle pressure, for a brief period following treatment to minimize swelling and reduce pain.
- The health care professional should instruct the patient to promptly report to her/him any evidence of problems possibly associated with the use of JUVÉDERM® VOLBELLA® XC.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® VOLBELLA® XC injectable gel is a smooth, clear, colorless, hyaluronic acid (HA) gel that contains a small quantity of local anesthetic (lidocaine). HA is a naturally occurring sugar found in the human body. The role of HA in the skin is to deliver nutrients and help the skin retain its natural moisture and softness. JUVÉDERM® VOLBELLA® XC injectable gel is manufactured using VYCROSS® technology during which, a small amount of the biodegradable compound BDDE is added to crosslink the HA in the gel. This results
in a specialized smooth-gel filler. Results at the treatment site are long lasting for up to 1 year with optimal improvement (over half of the subjects in the clinical study received a touch-up treatment).
How does it work?
JUVÉDERM® VOLBELLA® XC is a crystal-clear gel that is injected directly into the under-eye hollows (see Figure 1) using an ultrafine needle or cannula to improve the appearance of under-eye hollows in adults over the age of 21. The lidocaine in the gel reduces discomfort from the injection.
Are there any reasons why I should not receive JUVÉDERM® VOLBELLA® XC injectable gel?
Your doctor will ask about your medical history to determine if JUVÉDERM® VOLBELLA® XC is right for you. You should not use JUVÉDERM® VOLBELLA® XC if:
- You have severe allergies, marked by a history of severe reactions (anaphylaxis) or history or presence of multiple severe allergies. Use may result in an allergic reaction.
- You are allergic to lidocaine, use may result in an allergic reaction.
- If you have previous experience with allergic reactions to HA fillers. Use may result in an allergic reaction.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand to help avoid unsatisfactory results and complications:
- Juvéderm® Volbella® XC should only be injected into under-eye hollows by doctors who have completed the necessary training for this treatment area. To find a doctor, visit https://www.juvederm.com/find-a-specialist. Doctors who complete the training will be listed with a symbol.
- Minimize strenuous exercise and exposure to extensive sun or heat within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are using any medication that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning laser treatment, chemical peeling, or any other procedure after treatment with JUVÉDERM® VOLBELLA® XC. There is a possible risk of an inflammatory reaction at the treatment site.
- Tell your doctor which areas of your face you would like to have treated. This product is intended for use in the under-eye hollows area. The safety and effectiveness for treatment in areas other than the lips, perioral area, and under-eye hollows have not been established in controlled clinical studies.
- Tell your doctor about any medicines you are taking. You may have a greater risk of developing an infection if you use JUVÉDERM® VOLBELLA® XC while taking any medication that reduces your body’s natural defense system. This includes medicines to treat HIV and AIDs, autoimmune diseases such as rheumatoid arthritis and Crohn’s disease, chemotherapy for cancer, and steroids like prednisone. Use may result in an increased risk of infection.
- Tell your doctor if you are pregnant or breastfeeding. The safety for use during pregnancy, or in women who are breastfeeding, has not been studied.
- Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® VOLBELLA® XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars
- Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® VOLBELLA® XC in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
Troubleshooting
When should I call my doctor?
Call your doctor immediately if you have:
1) Changes in your vision
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
3) White appearance of the skin
4) Unusual pain during or shortly after treatment Be sure to call your doctor if you have:
1) Significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment 4) Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
JUVÉDERM® VOLBELLA® XC (also known as JUVÉDERM®
VOLBELLA® with Lidocaine) has been marketed outside the United
States since 2012 and in the United States since 2016.
The following AEs were received from post market surveillance for JUVÉDERM® VOLBELLA® with lidocaine with a frequency of 5 events or more and were not observed in the clinical studies; this includes reports received globally from all sources including scientific journals and voluntary reports. All AEs obtained through post market surveillance are listed in order of number of reports received: edema, non-inflammatory nodule, inflammatory reaction, pain, inflammatory nodule/granuloma, allergic reaction, loss/lack of correction, hematoma, unsatisfactory result, skin discoloration, infection, neurological symptoms such as increase or decrease in sensation, device migration, vascular occlusion, dermatitis, anxiety, blister, dry skin, varied injuries, abscess, overcorrection, herpes, flu-like symptoms, headache, drainage, scarring, angioedema, vision abnormalities, bleeding, malaise, necrosis, cyst, acne, dizziness, dyspnea, lymphadenopathy, autoimmune disorder exacerbation, calcification, vision loss, anaphylactic reaction, depression, telangiectasia, extrusion, and syncope.
In many cases the symptoms resolved without any treatment. Reported treatments included the use of (in alphabetical order): analgesics, antibiotics, antifungals, antihistamines, antiviral, arnica, ACE inhibitors, drainage, eye drops, hyaluronidase, ice, laser treatment, massage, NSAIDs, petroleum jelly, steroids, ultrasound therapy, vasodilators, and warm compress. Outcomes for these reported events ranged from resolved to ongoing at the time of last contact.
Vision abnormalities have been reported following injection of JUVÉDERM® VOLBELLA® XC into the glabella, lip, cheek and/or periorbital area, with a time to onset ranging from immediate to 2 months following injection. Reported treatments include antibiotics, anti-inflammatories, hyaluronidase, NSAIDs, and steroids. Outcomes ranged from resolved to ongoing at the time of last contact. (see WARNINGS section). Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Allergan Product Surveillance Department at 1-877 345 5372.
Post-treatment Checklist
What should I expect following the procedure?
In the JUVÉDERM® VOLBELLA® XC clinical trial, the most common side effects were temporary responses at the treatment site such as tenderness, bruising, swelling, lumps/bumps, redness, and pain. These side effects usually lasted 1 week or less. See Section 7 for additional information on side effects seen in the clinical study.
Your doctor will also tell you what to expect following treatment with JUVÉDERM® VOLBELLA® XC. Within the first 24 hours, you should minimize strenuous exercise and exposure to extensive sun, heat, and alcoholic beverages. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
Will I need more than one treatment to achieve my desired results? You should discuss your treatment goals and plan with your doctor. In the clinical study, 61% of subjects treated with JUVÉDERM® VOLBELLA® XC received a touch-up treatment 1 month after initial treatment in order to achieve the desired results.
Do the results last forever?
No. While individual results may vary, in the clinical study, the resultslasted for 1 year in the majority of subjects. Repeat injections are usually needed to maintain your desired result.
User Assistance Information
If you believe that you have experienced a serious problem related to JUVÉDERM® VOLBELLA® XC injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects. You may also report the occurrence of any adverse events to the Food and Drug Administration through the MedWatch Program: https://www.accessdata.fda.gov /scripts/medwatch/index.cfm
What should I do if I have additional questions? For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Vollure
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
JUVÉDERM® VOLLURE™ XC injectable gel is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of cross-linked hyaluronic acid (HA) produced by Streptococcus species of bacteria, formulated to a concentration of 17.5 mg/mL and 0.3% w/w lidocaine in a physiologic buffer.
Indication
JUVÉDERM® VOLLURE™ XC injectable gel is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds) in adults over the age of 21.
How Supplied
JUVÉDERM® VOLLURE™ XC injectable gel is supplied in individual treatment syringes with 30-G needles for single-patient use and ready for injection (implantation). The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is open or damaged.
Self Life and Storage
JUVÉDERM® VOLLURE™ XC injectable gel must be used prior to the expiration date printed on the label. Store at room temperature (up to 25ºC/77ºF). DO NOT FREEZE.
JUVÉDERM® VOLLURE™ XC injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan Product Support immediately at 1-877-345-5372.
To place an order, contact Allergan at 1-800-377-7790.
Contraindications
- JUVÉDERM® VOLLURE™ XC injectable gel is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® VOLLURE™ XC contains trace amounts of Gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® VOLLURE™ XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- JUVÉDERM® VOLLURE™ XC injectable gel must not be injected into blood vessels. Introduction of the product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft-tissue fillers; for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly, and apply the least amount of pressure necessary. Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and, possibly, evaluation by an appropriate health care professional specialist, should an intravascular injection occur (see Health Care Professional Instructions #13).
- Product use at specific sites in which an active infiammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection site responses consist mainly of short-term infiammatory symptoms starting early after treatment and lasting ≤ 30 days. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® VOLLURE™ XC injectable gel is packaged for single-patient use. Do not resterilize. Do not use if package is open or damaged.
- In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft-tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- The safety and effectiveness for the treatment of anatomic regions other than facial wrinkles and folds have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® VOLLURE™ XC is to be used as supplied. Modi cation or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, or in patients under 22 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- JUVÉDERM® VOLLURE™ XC injectable gel should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-in ammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- Patients may experience late-onset adverse events with use of dermal llers, including JUVÉDERM® VOLLURE™ XC. Refer to ADVERSE EVENTS section for details.
- After use, treatment syringes and needles are biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® VOLLURE™ XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan Product Support at 1-877-345-5372.
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® VOLLURE™ XC, there is a possible risk of eliciting an in ammatory reaction at the implant site. An in ammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A. US Pivotal Study of JUVÉDERM® VOLLURE™ XC In a multicenter, randomized, double-blind, within-subject controlled clinical trial to evaluate the safety and effectiveness of JUVÉDERM® VOLLURE™ XC versus the control (an FDA-approved cross-linked hyaluronic acid dermal ller which is legally marketed with similar indications) for the correction of moderate to severe nasolabial folds (NLFs), 123 subjects received treatment with JUVÉDERM® VOLLURE™ XC in 1 NLF and control in the other NLF. Touch-up treatment, if needed to achieve optimal correction, occurred approximately 30 days after the initial injection. Subjects were allowed an asymmetry correction treatment between 9 and 15 months after the initial treatment and a repeat treatment 12 to 18 months after initial treatment.
Subjects used preprinted diary forms to record specific signs and symptoms of injection site responses (ISRs) experienced during the 30 days following the initial treatment, touch-up treatment (if performed), asymmetry correction (if performed), and repeat treatment. Subjects were instructed to rate each ISR listed on the diary as Mild, Moderate, Severe, or None.
• Mild ISRs were defined as symptoms causing little, if any, discomfort leading to little, if any, effect on daily activities.
• Moderate ISRs were defined as symptoms causing some discomfort leading to some effect on daily activities.
• Severe ISRs were defined as symptoms causing great discomfort leading to compromised performance of daily activities.
The severity and duration of all ISRs reported by > 5% of subjects who completed post-treatment diary forms after initial treatment are summarized in Table 1 and Table 2, respectively. Subjects reported the severity of their ISRs as mild, moderate, or severe. Most of the individual ISRs were mild to moderate in severity and lasted less than 1 week after initial treatment, asymmetry correction, and repeat treatment with JUVÉDERM® VOLLURE™ XC; some of the ISRs lasted 8-30 days. The most common ISRs that lasted for 8-30 days after initial treatment were: rmness (42.6%, 46/108), lumps/ bumps (36.0%, 36/100), and discoloration (24.2%, 8/33). For most of the individual ISR types, subjects reported signi cantly fewer severe ISRs for JUVÉDERM® VOLLURE™ XC than for the control product. The incidence of ISRs reported after the asymmetry correction/repeat treatment was generally lower than that reported after initial treatment (Table 3).
Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe, as shown in Figure A.
STEP 2: Insert needle Hold the syringe body and firmly insert the hub of the needle (provided in the JUVÉDERM® VOLLURE™ XC package) into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle by turning it firmly in a clockwise direction (see Figure B) until it is seated in the proper position, as shown in Figure C.
NOTE: If the position of the needle cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle cap in the other. Without twisting, pull in opposite directions to remove the needle cap, as shown in Figure E.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
Treatment Procedures
It is recommended that the following information be shared with patients:
- Within the first 24 hours, patients should avoid strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites.
- To report an adverse reaction, phone the Allergan Product Support Department at 1-877-345-5372.
Injection Technique
1. JUVÉDERM® VOLLURE™ XC injectable gel is a smooth, crosslinked, cohesive, injectable gel formulation, injected using a 30-G ½" needle into the mid to deep dermis for versatility in the correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental “touch-up” implantations may be required to achieve and maintain maximum correction.
3. The patient’s soft-tissue deficiencies should be characterized with regard to etiology, distensibility, stress at the site, and depth of lesion. Pretreatment photographs are recommended.
4. Supplementary anesthesia may be used for additional pain management during and after injection.
5. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product fiows out of the needle.
6. After insertion of the needle, and just before injection, the plunger rod should be withdrawn slightly to aspirate and verify the needle is not intravascular.
7. After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
8. The injection technique may vary with regard to the angle and orientation of the bevel, the depth of injection, and the quantity administered. Different techniques such as serial puncture, tunneling, fanning, cross-hatching or a combination has been used to achieve optimal results. Injecting the product too superficially may result in visible lumps and/or discoloration.
9. Inject JUVÉDERM® VOLLURE™ XC by applying even pressure on the plunger rod while slowly moving the needle. It is important that the injection be stopped before the needle is pulled out of the skin to prevent material from leaking out or being placed too superficially in the skin. The wrinkle should be lifted and reduced by the end of the injection.
10. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle.
11. The typical total volume to achieve optimal correction of moderate to severe nasolabial folds is 1.7 mL per treatment site. To maintain optimal correction, approximately one-third of the volume per treatment site is needed at repeat treatment.
12. Correct to 100% of the desired volume effect. Do not overcorrect. The degree and duration of the correction depend on the character of the defect treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection volume and technique. Markedly indurated defects may be dif cult to correct.
13. If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1 (See WARNINGS section.)
14. When the injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If overcorrection occurs, massage the treated area against the underlying superficial bone or between your fingers to obtain optimal results.
15. With patients who have localized swelling, the degree of correction is sometimes difficult to judge at the time of treatment. In these cases, it is better to invite the patient back to the offie for a touch-up treatment.
16. After the initial treatment, an additional treatment may be necessary to achieve the desired level of correction. The same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as wrinkle severity, skin elasticity, and dermal thickness at the treatment site.
17. Patients may experience mild to moderate injection site responses, which typically resolve within 1 week. If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a brief period.
18. The health care professional should instruct the patient to promptly report any evidence of problems possibly associated with the use of JUVÉDERM® VOLLURE™ XC
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® VOLLURE™ XC injectable gel is a smooth, clear, colorless hyaluronic acid (HA) gel that contains a small quantity of local anesthetic (lidocaine). HA is a naturally occurring sugar found in the human body. The role of HA in the skin is to help retain natural moisture and softness. The lidocaine helps to improve the comfort of the injection. JUVÉDERM® VOLLURE™ XC injectable gel is manufactured using VYCROSS® technology to give a specialized smooth-gel filler that produces long-lasting results for up to 18 months at the treatment site.
What is it for?
JUVÉDERM® VOLLURE™ XC is injected with an ultrafine needle into areas of facial tissue where moderate to severe facial wrinkles and folds (such as nasolabial folds) occur.
How does it work?
As you age, wrinkles develop on your face, and nasolabial folds may become more visible. JUVÉDERM® VOLLURE™ XC is designed to temporarily reverse signs of aging by adding subtle volume to facial wrinkles and folds (such as nasolabial folds) and restoring a smoother appearance to the face in patients over the age of 21. The lidocaine in the gel improves the comfort of the injection by reducing sensitivity to pain.
Are there any reasons why I should not receive JUVÉDERM® VOLLURE™ XC injectable gel?
Your doctor will ask about your medical history to determine if JUVÉDERM® VOLLURE™ XC is right for you. You should not use JUVÉDERM® VOLLURE™ XC if:
• You have severe allergies with a history of severe reactions (anaphylaxis) or history or presence of multiple severe allergies. Use may result in an allergic reaction.
• You are allergic to lidocaine or to the proteins used to make the HA in JUVÉDERM® VOLLURE™ XC (Gram-positive bacterial proteins). Use may result in an allergic reaction. If you are not sure about your medical history concerning these allergies, please discuss further with your doctor.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand in order to help avoid unsatisfactory results and complications:
- Avoid strenuous exercise, exposure to extensive sun or heat, and consumption of alcoholic beverages within the first 24 hours following treatment. These may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are using any medication that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning laser treatment, chemical peeling, or any other procedure after treatment with JUVÉDERM® VOLLURE™ XC. There is a possible risk of an inflammatory reaction at the treatment site.
- Tell your doctor which areas of your face you would like to have treated. This product is intended for use in moderate to severe facial wrinkles and folds such as nasolabial folds. The safety and effectiveness for treatment in other areas have not been established in controlled, clinical studies.
- Tell your doctor if you are on therapy used to decrease the body’s immune response. Use may result in an increased risk of infection.
- Tell your doctor if you are pregnant or breastfeeding. The safety for use during pregnancy, or in women who are breastfeeding, has not been studied.
- Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® VOLLURE™ XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
- Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® VOLLURE™ XC in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
Troubleshooting
When should I call my doctor?
Call your doctor immediately if you have:
1) Changes in your vision
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
3) White appearance of the skin
4) Unusual pain during or shortly after treatment Be sure to call your doctor if you have:
1) Significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment 4) Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
JUVÉDERM® VOLLURE™ XC has been marketed in the United States since 2017. Outside the United States, JUVÉDERM® VOLLURE™ XC is known as JUVÉDERM® VOLIFT® with Lidocaine and has been marketed since 2011.
The following AEs were received from postmarket surveillance on the use of JUVÉDERM® VOLLURE™ XC with a frequency of 5 events or more and were not observed in the clinical study; this includes reports received globally from all sources including scienti c journals and voluntary reports. All AEs obtained through postmarket surveillance are listed in order of number of reports received: edema, non-in ammatory nodule, in ammatory reaction, pain, in ammatory nodule/granuloma, lack/loss of correction, allergic reaction, hematoma, unsatisfactory result, vascular occlusion, skin discoloration, infection, anxiety, device migration, neurological symptoms such as increase or decrease in sensation, dermatitis, varied injuries, blister, abscess, u-like symptoms, angioedema, headache, drainage, necrosis, herpes, dry skin, overcorrection, scarring, vision abnormalities, bleeding, acne, cysts, malaise, lymphadenopathy, autoimmune disorder exacerbation, dizziness, telangiectasia, extrusion, calci cation, depression, syncope, and anaphylactic reaction. In addition, 1 report of stroke after injections in an unspeci ed area with multiple dermal llers were reported.
In many cases the symptoms resolved without any treatment. Reported treatments for these events included the use of (in alphabetical order): analgesics, anesthetics, anti-allergy medications, antibiotics, antifungal, antihistamines, antiin ammatory medications, antiviral, arnica, aspiration, ACE inhibitors, drainage, hyaluronidase, hyperbaric oxygen treatment, ice, laser treatment, massage, nitrates, oral and topical corticosteroids, petroleum jelly, ultrasound therapy, vasodilators, and warm compress. Outcomes for these reported adverse events ranged from resolved to ongoing at the time of last contact.
Vision abnormalities have been reported following injection of JUVÉDERM® VOLLURE™ XC into the cheek, chin, nasolabial folds, oral commissures, pre-jowl area, lips, mouth, and/or periorbital area, with a time to onset ranging from immediate to 2 months following injection. Reported treatments include antibiotics, anti-in ammatories, hyaluronidase, massage, steroids, warm compress, and vasodilators. Outcomes ranged from resolved to ongoing at the time of last contact (see WARNINGS section).
Delayed-onset in ammation near the site of dermal ller injections is one of the known adverse events associated with dermal llers. Cases of delayed-onset in ammation have been reported to occur at the dermal ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in ammation was responsive to treatment or resolved on its own. Adverse reactions should be reported to Allergan Product Surveillance Department at 1-877-345-5372.
Post-treatment Checklist
What should I expect following the procedure?
In the JUVÉDERM® VOLLURE™ XC clinical trial, the most common side effects were temporary reactions at the injection site such as firmness, swelling, tenderness to touch, lumps/bumps, redness, pain, bruising, itching, and discoloration. These side effects usually lasted 1 week or less. See Section 7 for additional information on side effects seen in the clinical study. Your doctor will tell you what to expect following treatment with JUVÉDERM® VOLLURE™ XC. Within the first 24 hours, you should avoid strenuous exercise, exposure to extensive sun or heat, and consumption of alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
Will I need more than one treatment to achieve my desired results?
You should discuss your treatment goals and plan with your doctor. In the JUVÉDERM® VOLLURE™ XC clinical study, 51% of subjects received a touch-up treatment 1 month after initial treatment in order to achieve the desired result.
Do the results last forever?
No. While individual results may vary, in the clinical study, the results lasted for 18 months in a majority (59%) of subjects treated with JUVÉDERM® VOLLU
User Assistance Information
If you believe that you have experienced a serious problem related to JUVÉDERM® VOLLURE™ XC injectable gel, you should call your doctor.
You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
What should I do if I have additional questions?
For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Volux
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
1. DEVICE DESCRIPTION JUVÉDERM® VOLUX™ XC injectable gel is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of hyaluronic acid (HA) produced by Streptococcus species of bacteria crosslinked with BDDE, formulated to a concentration of 25 mg/mL with 0.3% w/w lidocaine in a physiologic buffer.
Indication
JUVÉDERM® VOLUX™ XC injectable gel is indicated for subcutaneous and/or supraperiosteal injection for improvement of jawline definition in adults over the age of 21 with moderate to severe loss of jawline definition.
How Supplied
JUVÉDERM® VOLUX™ XC injectable gel is supplied in individual treatment syringes with 27-G needles for single-patient use and ready for injection (implantation). The TSK STERiGLIDE™ 25-G 1½" cannula is not supplied with JUVÉDERM® VOLUX™ XC but is available for purchase through Allergan. The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and nonpyrogenic. Do not resterilize. Do not use if package is open or damaged.
Self Life and Storage
JUVÉDERM® VOLUX™ XC injectable gel should not be used after the expiration date printed on the label.
Store at room temperature (up to 25°C/77°F). DO NOT FREEZE.
JUVÉDERM® VOLUX™ XC injectable gel has a clear appearance. In the event that a syringe contains material that is not a clear, colorless gel without visible particulates, do not use the syringe; notify Allergan Product Surveillance immediately at 1-877-345-5372.
To place an order, contact Allergan at 1-800-377-7790.
Contraindications
- JUVÉDERM® VOLUX™ XC is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- JUVÉDERM® VOLUX™ XC contains trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- JUVÉDERM® VOLUX™ XC contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- The product must not be injected into blood vessels. Introduction of JUVÉDERM® VOLUX™ XC injectable gel into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting the product, for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events (AEs) associated with the intravascular injection of injectable gels in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see HEALTH CARE PROFESSIONAL INSTRUCTIONS #17).
- Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection site responses (ISRs) consist mainly of short-term inflammatory symptoms and generally resolve within 2 weeks. Refer to the ADVERSE EVENTS section for details.
Precautions
- JUVÉDERM® VOLUX™ XC injectable gel is packaged for singlepatient use. Do not resterilize. Do not use if package is open or damaged.
- In order to minimize the risk of potential complications, this product should only be used by health care professionals who have been trained in facial anatomy and vasculature, safe injection techniques, and identification and management of potential AEs, including intravascular complications.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injections with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies and a toxicological risk assessment, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (132 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- This product is intended for improving jawline definition. The safety and effectiveness for the treatment of anatomic regions in other areas of the body have not been established in controlled clinical studies.
- Injection of more than 9 mL of JUVÉDERM® VOLUX™ XC for improvement of jawline definition has not been studied.
- As with all transcutaneous procedures, injections of this product carry a risk of infection. Standard precautions associated with injectable materials should be followed.
- JUVÉDERM® VOLUX™ XC is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, or pigmentation disorders has not been studied.
- JUVÉDERM® VOLUX™ XC should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- Patients may experience late onset AEs with use of injectable gel implants, including JUVÉDERM® VOLUX™ XC. Refer to ADVERSE EVENTS section for details.
- After use, treatment syringes and needles are biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- JUVÉDERM® VOLUX™ XC injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan Product Surveillance at 1-877-345-5372.
- JUVÉDERM® VOLUX™ XC should only be used by health care professionals who have appropriate experience and who are knowledgeable about the anatomy and the product for use in the jawline.
- If laser treatment, chemical peel, or any other procedure based on active dermal response is considered after treatment with JUVÉDERM® VOLUX™ XC, there is a possible risk of eliciting an inflammatory reaction at the implant site. An inflammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A. US Pivotal Study of JUVÉDERM® VOLUX™ XC In the randomized, controlled, multicenter clinical study to evaluate the safety and effectiveness of JUVÉDERM® VOLUX™ XC for improving jawline definition, 156 participants were randomized to treatment and received injections in the jaw area (pre- and post-jowl sulci, chin, marionette lines, and mandible) during the primary phase of the study. Touch-up treatments occurred approximately 30 days after initial injection, if needed. After the 6-month blinded “no-treatment” control period, control participants were offered treatment; 42 control participants elected to receive treatment. Treatment group participants were offered a maintenance treatment 12 months after the last treatment. A total of 87 treatment group participants opted for the maintenance treatment.
Participants used electronic diaries to record specific signs and symptoms of ISRs experienced during the 30 days after the initial, touch-up, and maintenance treatments. Participants were instructed to rate each ISR listed on the diary as Mild, Moderate, Severe, or None.
• Mild ISRs were defined as symptoms causing little, if any, discomfort leading to little, if any, effect on daily activities.
• Moderate ISRs were defined as symptoms causing some discomfort leading to some effect on daily activities.
• Severe ISRs were defined as symptoms causing great discomfort leading to compromised performance of daily activities. The severity and duration of all ISRs reported by > 5% of participants after initial treatment (from both the treatment and control groups) are summarized in Table 1.
Most ISRs were mild or moderate (75%, 147/196 for any ISRs after initial treatment), and their duration was short lasting (14 days or less). A total of 35% (69/196) of ISRs lasted between 15 to 30 days. The incidence, severity, and duration of ISRs reported after the touch-up and maintenance treatments were similar to those reported after initial treatment.
Clinical Trials
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Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe, as shown in Figure A.
STEP 2: Insert needle Hold the syringe body and firmly insert the hub of the needle (provided in the JUVÉDERM® VOLUX™ XC package) or cannula into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle or cannula by turning it firmly in a clockwise direction until it is seated in the proper position, as shown in Figure C.
NOTE: If the position of the needle or cannula cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle or cannula cap in the other. Without twisting, pull in opposite directions to remove the needle or cannula cap, as shown in Figure E.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental touch-up injections may be required to achieve and maintain optimal effect.
Treatment Procedures
It is recommended that the following information be shared with patients:
- Avoid applying makeup for 12 hours after treatment. Within the first 24 hours, patients should avoid strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites.
- To report an adverse reaction, notify Allergan Product Surveillance at 1-877-345-5372.
Injection Technique
1. JUVÉDERM® VOLUX™ XC injectable gel is a highly crosslinked, smooth gel formulation that can be injected using a fine gauge needle (e.g., 27-G) or cannula (e.g., 25-G) to improve jawline definition.
2. The TSK STERiGLIDE™ 25-G 1½" cannula was used in the clinical trial and is the only cannula recommended for use with JUVÉDERM® VOLUX™ XC.
3. Educational resources are available through the Allergan Medical Institute, which provides training in facial anatomy and vasculature, effective patient assessment, safe injection techniques, and identification and management of potential AEs, including vascular complications. Health care practitioners may contact Allergan for educational and training resources.
4. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental touch-up injections may be required to achieve and maintain optimal effect.
5. Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual field testing.
6. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
• Ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines1
• Identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic AE related to soft tissue filler injection
• Conducting a basic neurologic examination in the event of an ophthalmic AE due to the association of such events with central nervous system deficits
7. The patient’s treatment goals should be characterized by improvement of jawline definition. Pretreatment photographs are recommended.
8. Supplementary anesthesia may be used for additional pain management during and after injection.
9. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product flows out of the needle.
10. After insertion of the needle/cannula, and just before injection, retract the plunger rod to slightly aspirate and verify the needle/ cannula is not intravascular. If blood is withdrawn, this could indicate intravascular placement, therefore stop immediately, reposition the needle/cannula and repeat the retraction step again. The absence of blood does not necessarily exclude intravascular placement. Therefore, it is important to inject the product slowly and apply the least amount of pressure necessary.
11. After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
12. The injection technique may vary with regard to the angle and orientation of the bevel, injection depth, and the quantity administered. Tunneling, serial puncture, and bolus injections are the most common technique used to achieve optimal results. Injecting the product too superficially may result in visible lumps and/ or discoloration
13. Inject JUVÉDERM® VOLUX™ XC by applying even pressure on the plunger rod. It is important that the injection be stopped before the needle/cannula is pulled out of the skin to prevent material from leaking out or being placed too superficially in the skin.
14. If the needle/cannula is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle/cannula.
15. The typical volume to achieve optimal improvement in jawline definition is 6.8 mL, which was the median total volume injected for initial and touch-up treatments combined and may vary depending on the goals the patient wishes to achieve. Injection volumes after maintenance treatment tended to be lower, with the typical injection volume to maintain optimal effect being 3.0 mL.
16. Inject to 100% of the desired correction. Do not over-inject. The degree and duration of the effect depend on the character of the area being treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection technique. Markedly indurated defects may be difficult to treat.
17. If immediate blanching occurs, the injection should be stopped, and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
18. When injection is completed, the treated site should be gently massaged so that it conforms to the contour ofthe surrounding tissues. If over-injection occurs, massage the area with your fingers or against the underlying superficial bone to obtain optimal results.
19. With patients who have localized swelling, the degree of effect is sometimes difficult to judge at the time of treatment. In this case, it is better to invite the patient back to the office for a touch-up treatment.
20. After the initial treatment, an additional treatment may be necessary to achieve the desired level of effect. If further treatment is needed, the same procedure should be repeated until a satisfactory result is
obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors, such as treatment goals, skin elasticity, and dermal thickness at the treatment site.
21. Patients may experience mild to moderate ISRs after treatment, which typically resolve within 2 weeks. Ice using gentle pressure for a brief period following treatment to minimize swelling and reduce pain.
22. The health care professional should instruct the patient to promptly report to her/him regarding any evidence of problems possibly associated with the use of JUVÉDERM® VOLUX™ XC.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
JUVÉDERM® VOLUX™ XC injectable gel is a smooth, clear, colorless hyaluronic acid (HA) gel that contains a small quantity of local anesthetic (lidocaine). HA is a naturally occurring sugar found in the human skin that retains moisture. JUVÉDERM® VOLUX™ XC injectable gel is manufactured using VYCROSS® technology, during which, a small amount of the compound BDDE is added to crosslink the HA in the gel. This results in a specialized and smooth injectable gel that produces jawline definition in the treated area.
How does it work?
JUVÉDERM® VOLUX™ XC is a clear gel that is injected directly in the jaw area using an ultrafine needle or cannula to improve jawline definition in adults over the age of 21 with moderate to severe loss of jawline definition (treatment area is depicted in Figure 1). The product provides volume to augment the shape and structure of the lower face, creating a smooth contour along the jawline and/or helping to reduce the appearance of jowls. The lidocaine in the gel improves the comfort of the injection by reducing sensitivity to pain.
Are there any reasons why I should not receive JUVÉDERM® VOLUX™ XC injectable gel?
Your doctor will ask about your medical history to determine if JUVÉDERM® VOLUX™ XC is right for you. You should not use JUVÉDERM® VOLUX™ XC if:
- You have severe allergies, marked by a history of severe reactions (anaphylaxis), or a history or presence of multiple severe allergies. Use may result in an allergic reaction.
- You are allergic to lidocaine. Use may result in an allergic reaction.
- You have previous experience with allergic reactions to HA fillers. Use may result in an allergic reaction.
Safety
What precautions should my doctor advise me about?
The following are important treatment considerations for you to discuss with your doctor and understand to help avoid unsatisfactory results and complications:
- Avoid applying makeup for 12 hours after treatment.
- Minimize strenuous exercise, exposure to extensive sun or heat, and alcoholic beverages within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are using any medication that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning to have laser treatment, chemical peel, or any other procedure after treatment with JUVÉDERM® VOLUX™ XC. There is a possible risk for an inflammatory reaction at the treatment site.
- Tell your doctor which areas of your face you would like to have treated. This product is intended for use in the jaw area (treatment area is depicted in Figure 1). The safety and effectiveness for treatment in other areas of the body have not been established in controlled, clinical studies.
- Tell your doctor about any medications you are taking. You may have a greater risk of developing an infection if you use JUVÉDERM® VOLUX™ XC while taking any medication that reduces your body’s natural defense system. This includes medicines to treat HIV and AIDS, autoimmune diseases such as rheumatoid arthritis and Crohn’s disease, chemotherapy for cancer, and steroids like prednisone. Use may result in an increased risk for infection.
- Tell your doctor if you are pregnant or breastfeeding. The safety for use during pregnancy or in women who are breastfeeding has not been studied.
- Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of JUVÉDERM® VOLUX™ XC injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
- Tell your doctor if you have a history of pigmentation disorders. The safety of JUVÉDERM® VOLUX™ XC in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
- Tell your doctor if you have already been injected with dermal fillers in the same area as the one(s) you are about to be treated for. This information helps your doctor decide when and whether you should get treatment with JUVÉDERM® VOLUX™ XC.
Troubleshooting
Call your doctor immediately if you have:
1) Changes in your vision
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
3) White appearance of the skin
4) Unusual pain during or shortly after treatment.
Be sure to call your doctor if you have:
1) Significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment 4) Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
The following AEs were received from postmarket surveillance on the use of JUVÉDERM® VOLUX™ XC outside the United States and were not observed in the clinical study; this includes reports received globally from all sources, including scientific journals and voluntary reports. These AEs, with a frequency of 5 events or more, are listed in order of prevalence: inflammatory reaction, edema, non-inflammatory nodule, pain, inflammatory nodule/granuloma, abscess, infection, hematoma, allergic reaction, device migration, neurological symptoms such as increase or decrease in sensation, loss/lack of correction, anxiety, vascular occlusion, skin discoloration, telangiectasia, drainage, dermatitis, lymphadenopathy, overcorrection, varied injuries, blister, scarring, nausea, unsatisfactory result, necrosis, headache, cyst, flu-like symptoms, bleeding, itching, redness, and autoimmune disorder exacerbation.
In many cases, AEs resolved without any treatment. Reported treatments for these events included (in alphabetical order): ACE inhibitors, antibiotics, anti-inflammatory drugs, analgesics, antiseptics, antihistamines, anti-bacterial drugs, anti-stress and sleeplessness drugs, anti-edema drugs, antithrombotics, anticoagulants, anxiolytics, calcium supplements, cold compress, drainage, hyaluronidase, hair growth stimulators, immunosuppressive drugs, immunotherapy, massage, muscle relaxants, NSAIDs (non-steroidal anti-inflammatory drugs), opioids, proton-pump inhibitors, rectal ointment, steroids, surgery, sedatives, ultrasound, and Vitamin B.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Adverse reactions should be reported to Allergan Product Surveillance at 1-877-345-5372.
Post-treatment Checklist
What should I expect following the procedure?
In the JUVÉDERM® VOLUX™ XC clinical study, the most common side effects were temporary responses at the treatment site, such as tenderness, lumps/bumps, pain, swelling, firmness, bruising, redness, itching, and discoloration. These side effects usually lasted 2 weeks or less. A total of 35% of the side effects lasted up to 30 days. See Section 8 for additional information on side effects seen in the clinical study. Your doctor will also tell you what to expect following JUVÉDERM® VOLUX™ XC injectable gel. Within the first 24 hours, you should minimize strenuous exercise, exposure to extensive sun or heat, and alcoholic beverages. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
Will I need more than one treatment to achieve my desired results?
You should discuss your treatment goals and plan with your doctor. In the clinical study, 83% of participants treated with JUVÉDERM® VOLUX™ XC received a touch-up treatment 1 month after initial treatment in order to achieve the desired aesthetic outcome. Among the 141 participants who completed the follow-up period, 87 participants (62%, 87/141) received maintenance treatment at 1 year.
Do the results last forever?
No. Hyaluronic acid fillers like JUVÉDERM® VOLUX™ XC are not permanent. The clinical study followed patients for one year and showed that the majority of patients (61%, 84/137) maintained their results for that one-year timeframe.
User Assistance Information
If you believe that you have experienced a serious problem related to JUVÉDERM® VOLUX™ XC injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
You may also report the occurrence of any adverse events to the Food and Drug Administration through the MedWatch Program: https://www.accessdata.fda. gov/scripts/medwatch/index.cfm
What should I do if I have additional questions? For further questions and information, please call Allergan at 1-800-766-0171.
Juvederm Skinvive
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
SKINVIVE™ by JUVÉDERM® injectable gel is a sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel implant. It consists of hyaluronic acid (HA) produced by Streptococcus species of bacteria crosslinked with 1,4-butanediol diglycidyl (BDDE) formulated to a concentration of 12 mg/mL with 0.3% w/w lidocaine in a physiologic buffer.
Indication
SKINVIVE™ by JUVÉDERM® injectable gel is indicated for intradermal injection to improve skin smoothness of the cheeks in adults over the age of 21.
How Supplied
SKINVIVE™ by JUVÉDERM® injectable gel is supplied in individual treatment syringes with 32 G needles for single-patient use and ready for injection (implantation). The volume in each syringe is as stated on the syringe label and on the carton. The contents of the syringe are sterile and non-pyrogenic. Do not resterilize. Do not use if package is open or damaged.
Self Life and Storage
SKINVIVE™ by JUVÉDERM® injectable gel should not be used after the expiration date printed on the label.
Store at room temperature (up to 25°C/77°F). DO NOT FREEZE.
SKINVIVE™ by JUVÉDERM® injectable gel has a clear appearance. In the event that a syringe contains material that is not clear, do not use the syringe; notify Allergan Product Support immediately at 1-877-345-5372.
To place an order, contact Allergan at 1-800-377-7790.
Contraindications
- SKINVIVE™ by JUVÉDERM® is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- SKINVIVE™ by JUVÉDERM® contains trace amounts of gram-positive bacterial proteins and is contraindicated for patients with a history of allergies to such material.
- SKINVIVE™ by JUVÉDERM® contains lidocaine and is contraindicated for patients with a history of allergies to such material.
Warnings
- The product must not be injected into blood vessels. Introduction of SKINVIVE™ by JUVÉDERM® injectable gel into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting the product, for example, after insertion of the needle, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events (AEs) associated with the intravascular injection of injectable gels in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care professional specialist should an intravascular injection occur (see HEALTH CARE PROFESSIONAL INSTRUCTIONS #12).
- Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.
- Injection site responses consist mainly of short-term inflammatory symptoms and generally resolve within 1 week. Refer to the ADVERSE EVENTS section for details.
Precautions
- SKINVIVE™ by JUVÉDERM® injectable gel is packaged for single-patient use. Do not resterilize. Do not use if package is open or damaged.
- In order to minimize the risk of potential complications, this product should only be used by health care professionals who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care professionals are encouraged to discuss all potential risks of soft tissue injections with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- Based on preclinical studies and a toxicological risk assessment, patients should be limited to 20 mL of any JUVÉDERM® injectable gel per 60 kg (130 lbs) body mass per year. The safety of injecting greater amounts has not been established.
- This product is intended for improving skin smoothness of the cheeks. The safety and effectiveness for the treatment of anatomic regions in other areas of the body have not been established in controlled clinical studies. • Injections of more than 6.0 mL of SKINVIVE™ by JUVÉDERM® (initial and touch-up treatment combined) for improvement of skin smoothness of the cheeks has not been studied.
- As with all transcutaneous procedures, injections of the product carry a risk of infection. Standard precautions associated with injectable materials should be followed.
- SKINVIVE™ by JUVÉDERM® is to be used as supplied. Modification or use of the product outside the Directions for Use may adversely impact the sterility, homogeneity, and performance of the product.
- The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years has not been established.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, or pigmentation disorders has not been studied.
- SKINVIVE™ by JUVÉDERM® should be used with caution in patients on immunosuppressive therapy.
- Patients who are using substances that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may, as with any injection, experience increased bruising or bleeding at injection sites.
- Patients may experience late onset AEs with use of injectable gel implants, including SKINVIVE™ by JUVÉDERM®. Refer to ADVERSE EVENTS section for details.
- After use, treatment syringes and needles are biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- SKINVIVE™ by JUVÉDERM® injectable gel is a clear, colorless gel without visible particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe; notify Allergan Product Surveillance at 1-877-345-5372.
- SKINVIVE™ by JUVÉDERM® should only be used by health care professionals who have appropriate experience and who are knowledgeable about the anatomy and the product for use in the face.
- If laser treatment, chemical peeling, or any other procedure based on active dermal response is considered after treatment with SKINVIVE™ by JUVÉDERM®, there is a possible risk of eliciting an inflammatory reaction at the implant site. An inflammatory reaction is also possible if the product is administered before the skin has healed completely after such a procedure.
- Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the LUER-LOK® and needle hub connection.
Adverse Experiences
A. US Pivotal Study of SKINVIVE™ by JUVÉDERM® In the randomized, controlled, multicenter clinical study to evaluate the safety and effectiveness of SKINVIVE™ by JUVÉDERM® for improving skin smoothness of the cheeks, 135 participants were randomized to treatment and received injections during the primary phase of the study. Touch-up treatments occurred approximately 30 days after initial injection, if needed. After the 1 month blinded “no-treatment” control period, control participants were offered treatment; 64 control participants elected to receive treatment. Treatment group participants were offered repeat treatment 6 months after the last treatment. A total of 79 treatment group participants opted for the repeat treatment.
Participants used electronic diaries to record specific injection site responses (ISRs) experienced during the 30 days after the initial, touch-up, and repeat treatments. ISRs are reactions associated with the injection procedure. Examples of ISRs are redness, pain after injection, tenderness to touch, firmness, swelling, lumps/bumps, bruising, itching and discoloration. Participants were instructed to rate each ISR listed on the diary as None, Mild, Moderate, or Severe.
- None or not applicable.
- Mild ISRs were defined as symptoms causing little, if any, discomfort leading to little, if any, effect on daily activities.
- Moderate ISRs were defined as symptoms causing some discomfort leading to some effect on daily activities.
- Severe ISRs were defined as symptoms causing great discomfort leading to compromised performance of daily activities. The severity and duration of all ISRs reported by > 5% of participants after initial treatment (from both the treatment and control groups) are summarized in Table 1. Most ISRs were mild, and their duration was short lasting (7 days or less). The incidence, severity, and duration of ISRs reported after the touch-up and repeat treatments were lower than those reported after initial treatment. Three participants (1.5%, 3/199) had mild (2/3) and moderate (1/3) lumps/bumps that resolved 12 to 15 months after treatment. Notreatment-related AEs were reported after repeat treatment.
Clinical Trials
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Directions For Assembly
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Assembly Of Needle To Syringe
STEP 1: Remove tip cap Hold syringe and pull tip cap off the syringe, as shown in Figure A.
STEP 2: Insert needle Hold the syringe body and firmly insert the hub of the needle (provided in the JSKINVIVE™ by JUVÉDERM®) or cannula into the LUER-LOK® end of the syringe.
STEP 3: Tighten the needle Tighten the needle or cannula by turning it firmly in a clockwise direction until it is seated in the proper position, as shown in Figure C.
NOTE: If the position of the needle or cannula cap is as shown in Figure D, it is not attached correctly. Continue to tighten until the needle is seated in the proper position.
STEP 4: Remove the needle cap Hold the syringe body in one hand and the needle or cannula cap in the other. Without twisting, pull in opposite directions to remove the needle or cannula cap, as shown in Figure E.
Pre-Treatment Guidlines
Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental touch-up injections may be required to achieve and maintain optimal effect.
Treatment Procedures
It is recommended that the following information be shared with patients:
- Avoid applying makeup for 12 hours after treatment. Within the first 24 hours, patients should avoid strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of the above may cause temporary redness, swelling, and/or itching at the injection sites.
- To report an adverse reaction, phone the Allergan Product Surveillance Department at 1-877-345-5372.
Injection Technique
1. SKINVIVE™ by JUVÉDERM® injectable gel is a crosslinked, soft, smooth gel formulation that can be injected using a fine gauge (e.g., 32 G) needle to improve skin smoothness of the cheeks.
2. Prior to treatment, the patient’s medical history should be obtained, and the patient should be fully apprised of the indications, contraindications, warnings, precautions, treatment responses, adverse reactions, and method of administration. Patients also should be advised that supplemental touch-up injections may be required to achieve and maintain optimal effect.
3. The patient’s treatment goals should be characterized by improvement of skin smoothness of the cheeks.
4. Supplementary anesthesia may be used for additional pain management during and after injection.
5. After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be prepped with alcohol or other antiseptic. Prior to injecting, depress the plunger rod until the product flows out of the needle.
6. After insertion of the needle into the skin, and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular.
7. After the first small amount of material has been injected into the patient, wait a full 3 seconds to allow the lidocaine to take effect before proceeding with the rest of the injection.
8. The injection technique may vary with regard to the angle and orientation of the bevel, the depth and spacing of injections, and the quantity administered. Microdroplet injections is the most common technique used to achieve optimal results. Injecting the product too superficially may result in visible lumps and/or discoloration.
9. Inject SKINVIVE™ by JUVÉDERM® by applying even pressure on the plunger rod. It is important that the injection be stopped before the needle is pulled out of the skin to prevent material from leaking out or being placed too superficially in the skin.
10. If the needle is blocked, do not increase the pressure on the plunger rod. Instead, stop the injection and replace the needle.
11. The typical volume to achieve optimal improvement in skin smoothness of the cheeks is 4.0 mL. Injection volumes after repeat treatment tended to be lower, with the typical injection volume to maintain optimal effect being 2.7 mL.
12. Microdroplet injections of 0.01 mL to 0.05 mL, spaced approximately 0.5 cm to 1 cm apart are recommended. However, this will vary based on the patient’s treatment goals.
3. Inject to 100% of the desired correction. Do not over-inject. The degree and duration of the effect depend on the character of the area being treated, the tissue stress at the implant site, the depth of the implant in the tissue, and the injection technique. Markedly indurated defects may be difficult to treat.
14. If immediate blanching occurs, the injection should be stopped, and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.1
15. When injection is completed, the treated site should be gently massaged so that it conforms to the contour of the surrounding tissues. If over-injection, visible lumps, or discoloration occurs, massage the area with your fingers or against the underlying superficial bone to obtain optimal results.
16. With patients who have localized swelling, the degree of effect is sometimes difficult to judge at the time of treatment. In this case, it is better to invite the patient back to the office for a touch-up treatment.
17. After the initial treatment, an additional treatment may be necessary to achieve the desired level of effect. If further treatment is needed, the same procedure should be repeated until a satisfactory result is obtained. The need for an additional treatment may vary from patient to patient and is dependent upon a variety of factors such as skin texture, skin elasticity, and dermal thickness at the treatment site.
18. Patients may experience mild to moderate injection site responses after treatment, which typically resolve within 7 days. Ice using gentle pressure for a brief period following treatment to minimize swelling and reduce pain.
19. The health care professional should instruct the patient to promptly report to her/him any evidence of problems possibly associated with the use of SKINVIVE™ by JUVÉDERM®.
Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is it?
SKINVIVE™ by JUVÉDERM® injectable gel is a smooth, clear, colorless hyaluronic acid (HA) gel that contains a small quantity of local anesthetic (lidocaine). HA is a naturally occurring sugar found in the human body that retains moisture in the skin. BDDE (1,4-butanediol diglycidyl ether) is used as a crosslinking agent. SKINVIVE™ by JUVÉDERM® injectable gel is manufactured by crosslinking the HA gel using a small amount of BDDE, an organic substance the body will naturally break down.
How does it work? SKINVIVE™ by JUVÉDERM® is injected into the cheeks using an ultrafine needle to restore skin smoothness (see Figure 1) for adults over the age of 21. The product injects HA to the cheeks which helps the skin retain its natural moisture and softness leading to an improvement in the skin smoothness of the cheeks. The lidocaine in the gel improves the comfort of the injection by reducing sensitivity to pain.
Are there any reasons why I should not receive SKINVIVE™ by JUVÉDERM® injectable gel treatment
Your doctor will ask about your medical history to determine if a treatment regimen with SKINVIVE™ by JUVÉDERM® gel is right for you. You should not use SKINVIVE™ by JUVEDERM® if:
- You have severe allergies, marked by a history of severe reactions (anaphylaxis) or history or presence of multiple severe allergies. Use may result in an allergic reaction.
- You are allergic to lidocaine or to the proteins used to make the HA in SKINVIVE™ by JUVÉDERM® (Gram-positive bacterial proteins). Use may result in an allergic reaction.
- If you have previous experience with allergic reactions to HA fillers. Use may result in an allergic reaction.
Safety
What precautions should my doctor advise me about? The following are important treatment considerations for you to discuss with your doctor and understand to help avoid unsatisfactory results and complications:
- Minimize strenuous exercise, exposure to extensive sun or heat, and alcoholic beverages within the first 24 hours following treatment. Exposure to any of these may cause temporary redness, swelling, and/or itching at the injection site.
- Tell your doctor if you are using any medication that can prolong bleeding, such as aspirin, ibuprofen, or other blood thinners. As with any injection, this may increase bruising or bleeding at the injection site.
- Tell your doctor if you are planning laser treatment, chemical peeling, or any other procedure after SKINVIVE™ by JUVÉDERM® injectable gel treatment. There is a possible risk of an inflammatory reaction at the treatment site.
- Tell your doctor which areas of your face you would like to have treated. This product is intended for improving skin smoothness of the cheeks. The safety and effectiveness for treatment in other areas of the body have not been established in controlled, clinical studies.
- Tell your doctor if you are on therapy used to decrease the body’s immune response. Use may result in an increased risk of infection.
- Tell your doctor if you are pregnant or breastfeeding. The safety for use during pregnancy, or in women who are breastfeeding, has not been studied.
- Tell your doctor if you have a history of excessive scarring (thick, hard scars). The safety of SKINVIVE™ by JUVÉDERM® injectable gel in patients with a history of excessive scarring has not been studied and may result in additional scars.
- Tell your doctor if you have a history of pigmentation disorders. The safety of SKINVIVE™ by JUVÉDERM® in patients with a history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
Troubleshooting
When should I call my doctor? Call your doctor immediately if you have:
1) Changes in your vision
2) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
3) White appearance of the skin
4) Unusual pain during or shortly after treatment
Be sure to call your doctor if you have:
1) Significant pain away from the injection site
2) Any redness and/or visible swelling that lasts for more than a few days
3) Any side effect that occurs weeks or months after treatment 4) Any other symptoms that cause you concern
Administration
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Post Marketing Surveillance
The following AEs were received from postmarket surveillance on the use of SKINVIVE™ by JUVÉDERM® outside the United States; this includes reports received globally from all sources including scientific journals and voluntary reports. These AEs, with a frequency of 5 events or more, are listed in order of prevalence: inflammatory reaction, inflammatory nodule, unsatisfactory result, loss/lack of correction, allergic reaction, anxiety, varied injuries, vascular occlusion, infection, dry skin, neurological symptoms such as increase/decrease in sensation, and abscess.
In many cases, AEs resolved without any treatment. Reported treatments for these events included (in alphabetical order): antibiotics, anticholinergics, anticoagulants, antihistamines, anti-inflammatories, antimetabolites, antivirals, arnica, blood thinners, hyaluronidase, ice, laser therapy, massage, radiofrequency therapy, steroids, ultrasound therapy, and warm compress.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Adverse reactions should be reported to Allergan Product Surveillance Department at (877) 345-5372.
Post-treatment Checklist
What should I expect following the procedure?
In the SKINVIVE™ by JUVÉDERM® clinical study, the most common side effects were temporary responses at the treatment site such as redness, lumps/bumps, swelling, bruising, tenderness, and pain. These side effects usually lasted 7 days or less, but 1.5% of the side effects lasted more than 30 days or longer. See Section 7 for additional information on side effects seen in the clinical study.
Your doctor will also tell you what to expect following SKINVIVE™ by JUVÉDERM® injectable gel treatment. Within the first 24 hours, you should minimize strenuous exercise, exposure to extensive sun or heat, and alcoholic beverages. Exposure to any of the above may increase temporary redness, swelling, and/or itching at the injection site. If there is swelling, you may need to place an ice pack over the swollen area. You should ask your doctor when makeup may be applied after your treatment.
13. Will I need more than one treatment to achieve my desired results?
You should discuss your treatment goals and plan with your doctor. The regimen with SKINVIVE™ by JUVÉDERM® may require multiple treatments to achieve the desired results. In the clinical study, 73% of participants treated with SKINVIVE™ by JUVÉDERM® received a touch-up treatment 1 month after initial treatment in order to achieve the desired aesthetic outcome.
14. Do the results last forever?
No. While individual results may vary, in the clinical study, the results lasted for 6 months in most participants. Repeat injections are usually needed to maintain your desired result.
User Assistance Information
If you believe that you have experienced a serious problem related to SKINVIVE™ by JUVÉDERM® injectable gel, you should call your doctor. You may also contact the Allergan Product Surveillance line during normal business hours at 1-877-345-5372 to report any side effects.
What should I do if I have additional questions?
For further questions and information, please call Allergan at 1-800-766-0171
RHA Redensity
PATIENT INSTRUCTION
PACKAGE INSERT
Description
RHA® Redensity is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogeneous and biodegradable gel implant of both crosslinked and non-crosslinked hyaluronic acid. It is produced with sodium Hyaluronic Acid (NaHA) with a concentration of 15 mg/g obtained from bacterial fermentation using the streptococcus equi bacterial strain, crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® Redensity also contains 0.3% lidocaine hydrochloride to reduce pain on injection
Indication
RHA® Redensity is indicated for injection into the dermis and super!cial dermis of the face, for the correction of moderate to severe dynamic perioral rhytids, in adults aged 22 years or older.
How Supplied
RHA® Redensity is supplied in individual blisters containing a 1 mL treatment syringe with two 30 G x ½” needles as indicated on the carton. The content of the syringe is sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged. Each syringe is packaged into a blister with two unique device identi!er traceability labels.
Self Life and Storage
RHA® Redensity must be used prior to the expiration date printed on the package.
Store at room temperature (up to 25°C/77°F). Do not expose to direct sunlight. DO NOT FREEZE.
Do not store partially used syringes.
Contraindications
- RHA® Redensity is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- RHA® Redensity contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- RHA® Redensity should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
- RHA® Redensity should not be used in patients with bleeding disorders.
Warnings
- RHA® Redensity must not be injected into blood vessels. Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue !llers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue !llers in the face have been reported and include temporary or permanent vision impairment or blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Product use at speci!c sites in which an active in"ammatory process (skin eruptions such as cysts, pimples, rashes, or hives), infection or skin injury is present should be deferred until the underlying process has been controlled.
- Treatment site reactions consist mainly of short-term in"ammatory symptoms (e.g., swelling, redness, tenderness, or pain) and generally resolve within 14 days. Refer to the ADVERSE EXPERIENCES section for details.
- In"ammatory reaction, anaphylactic reaction, edema, implant migration, acne, blisters, scarring, papules and delayed onset of granulomas have been reported following the use of dermal !llers.
Precautions
- In order to minimize the risks of potential complications, this product should only be used by experienced health care practitioners who have appropriate training in !ller injection techniques, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- The safety and effectiveness for the treatment of anatomic regions other than those described in the INTENDED USE / INDICATIONS section have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal !ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- The safety for use in sites in the presence of other implants (including permanent implants) has not been studied. • The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years of age has not been established.
- RHA® Redensity should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at RHA® Redensity injection sites. RHA® Redensity should be used with caution in patients who are using substances that can prolong bleeding (such as thrombolytics, anticoagulants, or inhibitors of platelet aggregation).
- Injection of RHA® Redensity into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with RHA® Redensity, there is a possible risk of eliciting an in"ammatory reaction at the implant site. This also applies if RHA® Redensity is administered before the skin has healed completely after such a procedure.
- RHA® Redensity is to be used as supplied. Modi!cation or use of the product outside the Instructions for Use may adversely impact the sterility, safety, homogeneity, or performance of the product.
- RHA® Redensity is packaged for single-use. Do not reuse a syringe after treatment. Do not re-sterilize.
- Do not use if package is opened or damaged. The sterility of the product is not guaranteed in the case of failure to comply with this precaution. Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer-lock and needle hub connection.
- RHA® Redensity is a clear, colorless gel without particulates. In the event the contents of a syringe show signs of separation and/or appears cloudy, do not use the syringe; contact Revance Therapeutics, Inc. 877-3REVNOW (877-373-8669)
Adverse Experiences
1. Clinical Evaluation of RHA® Redensity A multicenter, controlled, randomized, blinded, No-Treatment control, prospective clinical study compared the safety and effectiveness of RHA® Redensity versus a No-Treatment control for the treatment of moderate to severe dynamic perioral rhytids. The expected signs and symptoms that occur following the injection of a hyaluronic acid-based dermal !ller (i.e., Common Treatment Responses; CTR) were individually assessed by subjects in a preprinted 14-day diary after each injection. CTRs are commonly expected injection site responses which are temporally associated with injection of a dermal !ller. Events like redness, swelling, pain, bruising, tenderness, and lumps and bumps are examples of expected CTRs. Severe CTRs, or those lasting longer than 14 days or present on the last day of the subject diary, were evaluated for conversion to an adverse event. Subjects were asked to rate each CTR as None, Mild, Moderate or Severe:
- Mild: Little discomfort, no effect on daily activities, no medication or make-up required
- Moderate: some discomfort, some effect on daily activities, possibly medication or make-up required
- Severe: Great discomfort, daily activities compromised, very likely medication or make-up required CTRs by severity and duration are presented respectively, in Table 1 and Table 2.
- The most frequent CTRs were bruising, swelling, redness, !rmness, lumps/bumps and tenderness.
- More than 76% of the CTRs had resolved by Day 7.
- Nearly 90% of CTRs had resolved by Day 14 without treatment.
- Other than lumps/bumps, each type of CTR that was present on the last day of the 14-Day diary was present in less than 10% of subjects.
- For nearly all CTRs (more than 92%), the maximal severity reported was “Mild” or “Moderate”.
- Less than 6% of each CTR was reported as “Severe” by the subjects except for bruising (12%).
- When bruising persisted to the last day of the diary, all were deemed “Mild” by the treating investigator except 3 that were rated at “Moderate”.
None were “Severe”. More than 90% of Bruises had resolved by end of 14-day diary
Clinical Trials
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Directions For Assembly
Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual !eld testing. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
- ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines
- identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal !ller injection
- conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system de!cits.
Assembly Of Needle To Syringe
1. Remove the stopper from the syringe by pulling it off.
2. Insert the screw thread of the needle !rmly into the syringe end-piece.
3. Screw the needle clockwise, while maintaining slight pressure between the needle and the syringe. Continue screwing until the edge of the cap of the needle contacts the body of the syringe. There must be no space between these two parts. Failure to follow this instruction means that the needle could be ejected and/or leak at the Luer-lock.
5. Remove the needle’s protective cap by pulling it !rmly with one hand while holding the body of the syringe with the other.
Pre-Treatment Guidlines
- Prior to treatment, the patient should avoid taking medications or supplements which thin the blood (e.g., aspirin, nonsteroidal antiin"ammatory medications, St. John’s Wort, high doses of Vitamin E supplements, anti-coagulants) as these agents may increase bruising and bleeding at the injection site.
- Before starting treatment, a complete medical history should be taken from the patient and the patient should be counseled on appropriate indications, risks, and should be informed about the expected treatment results, and expected responses. The patient should be advised of the necessary precautions before commencing the procedure.
- Prior to treatment with RHA® Redensity the patient should be assessed for appropriate anesthetic treatment for managing comfort (e.g., topical anesthetic, local or nerve block). The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
- Sterile gloves are recommended while injecting RHA® Redensity.
- Before injecting, prime the needle by carefully pressing the syringe plunger until a small droplet of the gel is visible at the tip of the needle
Treatment Procedures
A patient information brochure is available on request, or via the website www.revance.com. It is recommended that the following information be shared with patients:
- Patients should be advised not to wear make-up during 12 hours following injection.
- Patient should be advised not to take high-dose Vitamin E, aspirin, anti-in"ammatories or anti-coagulants during the week prior to the injection. Patients must not discontinue such treatment without talking with their prescribing physician.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures (e.g. cold weather, sauna) at least within the 24 hours, or until initial swelling and redness has resolved. Exposure to any of the above may cause/ exacerbate and/or extend the duration of temporary redness, swelling, and/or itching at the treatment sites.
- Patients should notify the injector if any of the following occurs: - Changes in vision - Unusual pain during or shortly after treatment - Signi!cant pain away from the injection site - Signs of a stroke - Any redness and/or visible swelling that lasts for more than a week - Any side effect other than those described above or that occur weeks or months after injection
- Adverse reactions should be reported to Revance Therapeutics, Inc at 877-3REV-NOW (877-373-8669) and to [email protected].
Injection Technique
• RHA® Redensity can be administered by using a thin gauge needle (30 G x ½”) and with a number of different techniques that depend on the injector’s experience and preference, and patient characteristics.
A. Preclinical testing between the following needles brands (TSK HPC, TSK PRC, Terumo TW, Terumo ETW) and the syringe has con!rmed that the interoperability and compatibility is reliable and safe. Serial puncture: consists of multiple injections, evenly and closely spaced perpendicular to the lines. This technique is considered to be more precise, but may result in more discomfort for the patient due to the number of punctures.
B. Linear threading: the needle is fully introduced in the wrinkle or the fold, and the product is injected along the line, as a “thread”, while withdrawing (retrograde) or pushing (antegrade) the needle.
C. Fanning technique: the needle is introduced as for the Linear threading technique, and the product is injected along several closely spaced lines, by changing the direction of the needle, all using the same puncture site (the needle is not withdrawn).
• RHA® Redensity is injected slowly into the dermis. If the injection is made too deeply, i.e. into subcutaneous tissue, the correction may not be as expected. It is possible to tell when an injection is being made too deeply because subcutaneous tissue, unlike the dermis, does not offer any resistance to product injection, the injected product may not be visible as a raised elevation on the skin and correction of the lines may not be achieved.
• The injection should be stopped before withdrawing the needle from the skin, to prevent product from leaking out, or product misplacement (too super!cially in the skin).
• The volume to be injected depends on the correction to be performed, but it is important to not overcorrect. Based on the US clinical study, patients should be limited to 6.0 mL per patient per treatment session in perioral rhytids. The safety of injecting greater amounts has not been established.
• Any blanching appearing through the vascular "ow may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
• If the perioral lines need further treatment with RHA® Redensity, the same procedure should be repeated until a satisfactory result is obtained.
Sterile Needles
- After use, needles are potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical sharp devices (e.g. discard uncapped needles in approved sharps containers).
- Obtain prompt medical attention if injury with used needle occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not recap needles. Recapping by hand is a hazardous practice and should be avoided.
- RHA® Redensity is provided with 2 needles that do not contain engineered injury protection. Administration of RHA® Redensity requires direct visualization and complete and gradual insertion of the needle making engineered protection devices not feasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is RHA® Redensity™?
RHA® Redensity™ is an injectable gel (also called a dermal filler) used to treat moderate and severe lines and wrinkles around the mouth. It is injected in the moving (dynamic) area around the mouth (see Figure 1). It is approved for use in adults over 22 years of age.
RHA® Redensity™ is produced with hyaluronic acid (HA), using an advanced technology to obtain a soft and long-lasting injectable gel to smooth facial wrinkles and folds. Chains of HA are linked together through a chemical reaction triggered by a small quantity of BDDE to create the gel texture of RHA® Redensity™. The HA of the gel is made from a non-animal source.
RHA® Redensity™ contains a small amount of an anesthetic medicine (lidocaine), to help reduce discomfort during injection. 3 Hyaluronic acid (HA) is a naturally occurring substance found in the human body. Your body’s own HA helps maintain the skin’s structure and its natural feel.
How does it work?
RHA® Redensity™ is injected into the skin with an ultrafine needle to plump the skin to fill in and smooth away lines and wrinkles around the mouth (perioral rhytids). This smoothing effect has been shown to last 24 weeks (6 months) in 73% of the patients (137 out of 188 patients), and 52 weeks (12 months) in 67% of the patients (125 out of 188 patients). RHA® Redensity™ is not a permanent gel. It slowly goes away as the body absorbs the gel. The smoothing and plumping effect will gradually disappear.
Safety
Are there precautions that I should discuss with my doctor?
4 The following are important treatment considerations that you should discuss with your doctor. These hazards, if not avoided, could result in unsatisfactory results or complications.
- Tell your doctor if you are under 22 years of age. RHA® Redensity™ has not been studied in people younger than 22 and the effects are not known.
- Tell your doctor if you are pregnant (or plan to be) or breastfeeding. RHA® Redensity™ has not been studied in women who were pregnant or breastfeeding and the effects are not known.
- Tell your doctor if you are taking medicine that reduces your body’s ability to fight infection (immunosuppressive therapy). Taking this type of medicine may increase the risk of infection following the injection of RHA® Redensity™ or other dermal fillers.
- Be sure to tell your injecting doctor if you are using “blood thinners” (anticoagulants) or any other medications that affect bleeding. Do not stop taking them until you speak with the doctor who prescribed them for you. Tell your prescribing doctor that you are considering having your wrinkles treated with RHA® Redensity™. These blood thinning medications may cause increased bleeding and/or bruising in the treated area.
- Tell your doctor if you have a history of cold sores (herpes). Any injection, including RHA® Redensity™, in the general area may trigger a recurrence of your cold sores (herpes).
- Tell your doctor if you have an injury, or other skin condition near the injection site(s). Injection of a dermal filler in this situation may lead to a worsening of your condition or infection. You may have to wait until you are completely healed before using RHA® Redensity™.
- Tell your doctor if you have ever developed a thick tough scar (keloid) or had problems with skin discoloration. It is possible that injection of any dermal filler, including RHA® Redensity™, may make the skin thicker and change color. However, when RHA® Redensity™ was studied in patients with different skin tones (pale to dark), there were no reports of this happening.
- Tell your doctor if you have a history of pigmentation disorders. The safety of RHA® Redensity™ in patients with history of pigmentation disorders has not been studied. Use in these patients may result in changes in pigmentation.
- Tell your doctor if you have already been injected with dermal fillers in the same area as the one(s) you are about to be treated for. This information helps your doctor decide when and whether you should get treatment with RHA® Redensity™.
- Tell your doctor if you have recently had (within 6 months), or are considering, laser treatment, chemical peeling or any other facial procedure. Use of RHA® Redensity™ with these skin treatments may lead to an increased severity of the common treatment reactions such as redness, swelling, heat or pain in the area.
- You should not take Vitamin E, aspirin, or anti-inflammatories during the week prior to the injection. Taking these medications can thin your blood and may result in increased bleeding and/or more bruising in the treated area. If you have any additional questions about any topic in this section, please discuss further with your 5 doctor.
Troubleshooting
Call your doctor if you have any questions or concerns after your procedure. Call your doctor immediately if you have:
1) Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
2) Changes in your vision x Pain which increases after your treatment
3) Significant pain away from the injection site x Significant whitening or darkening of the skin
4) Any treatment reaction other than bruising, firmness, swelling, pain, tenderness, redness, lumps/bumps, itching, which occurs in the first two weeks
5) Any treatment reaction in the injected area, including lump or hardening under the skin, that appears weeks or months after your injection. The following are common reactions often seen after treatment with dermal fillers. They usually go away within 2 weeks. If you are concerned, or if they last more than 2 weeks, call your doctor:
• Bruising
• Swelling
• Redness
• Firmness
• Lumps/bumps
• Tenderness 11
• Change in skin color
• Pain
• Itching
Administration
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Post Marketing Surveillance
The following adverse events were reported as part of post-marketing surveillance on the use of RHA® Redensity outside the United States with a prevalence equal or superior to 1 occurrence for 100,000 syringes: edema, injection site masses (lumps and bumps), in"ammatory nodules (papules), skin swelling, skin induration, vascular skin disorder (such as vessel compression/occlusion), pain, ecchymosis, and in"ammatory reaction. Additionally, other less frequent adverse reactions have also been reported, and include dermal !ller overcorrection, allergic reaction, product misplacement, skin discoloration, skin necrosis, erythema, granuloma, injection site movement impairment/paraesthesia, skin atrophy and tenderness. Delayed-onset in"ammation near the site of dermal !ller injections is one of the known adverse events associated with dermal !llers. Cases of delayed-onset in"ammation have been reported to occur at the dermal !ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in"ammation was responsive to treatment or resolved on its own.
In many cases the symptoms resolved without any treatment. Reported treatments and procedures included the use of (in alphabetical order): analgesics, antibiotics, anti-histamines, anti-in"ammatories, anti-viral, implant dissolution (hyaluronidase), drainage, excision, incision, massage, and vasodilators.
Post-treatment Checklist
- When the injection is completed, the treated site may be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area !rmly between your !ngers or against an underlying area to obtain optimal results.
- If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period (e.g., 5-10 minutes). Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
- After use, syringes may be potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical biohazard devices. Obtain prompt medical attention if injury occurs.
User Assistance Information
In case you have any further questions, please contact Revance Therapeutics, Inc. at 877-3REVNOW (877-373-8669). www.revance.com RHA® Redensity™ is a registered trademark of TEOXANE S.A. TEOXANE S.A. - Rue de Lyon, 105 – CH 1203 Geneva (Switzerland)
RHA 2
PATIENT INSTRUCTION
PACKAGE INSERT
Description
RHA® Redensity 2 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogeneous and biodegradable gel implant of both crosslinked and non-crosslinked hyaluronic acid. It is produced with sodium Hyaluronic Acid (NaHA) with a concentration of 15 mg/g obtained from bacterial fermentation using the streptococcus equi bacterial strain, crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® Redensity also contains 0.3% lidocaine hydrochloride to reduce pain on injection.
Indication
RHA® Redensity is indicated for injection into the dermis and super!cial dermis of the face, for the correction of moderate to severe dynamic perioral rhytids, in adults aged 22 years or older.
How Supplied
RHA® Redensity 2 is supplied in individual blisters containing a 1 mL treatment syringe with two 30 G x ½” needles as indicated on the carton. The content of the syringe is sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged. Each syringe is packaged into a blister with two unique device identi!er traceability labels.
Self Life and Storage
RHA® Redensity 2 must be used prior to the expiration date printed on the package.
Store at room temperature (up to 25°C/77°F). Do not expose to direct sunlight. DO NOT FREEZE.
Do not store partially used syringes.
Contraindications
- RHA® Redensity 2 is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- RHA® Redensity 2 contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- RHA® Redensity 2 should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
- RHA® Redensity 2 should not be used in patients with bleeding disorders.
Warnings
- RHA® Redensity 2 must not be injected into blood vessels. Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue !llers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue !llers in the face have been reported and include temporary or permanent vision impairment or blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Product use at speci!c sites in which an active in"ammatory process (skin eruptions such as cysts, pimples, rashes, or hives), infection or skin injury is present should be deferred until the underlying process has been controlled.
- Treatment site reactions consist mainly of short-term in"ammatory symptoms (e.g., swelling, redness, tenderness, or pain) and generally resolve within 14 days. Refer to the ADVERSE EXPERIENCES section for details.
- In"ammatory reaction, anaphylactic reaction, edema, implant migration, acne, blisters, scarring, papules and delayed onset of granulomas have been reported following the use of dermal !llers.
Precautions
- In order to minimize the risks of potential complications, this product should only be used by experienced health care practitioners who have appropriate training in !ller injection techniques, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- The safety and effectiveness for the treatment of anatomic regions other than those described in the INTENDED USE / INDICATIONS section have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal !ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- The safety for use in sites in the presence of other implants (including permanent implants) has not been studied.
- The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years of age has not been established.
- RHA® Redensity 2 should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at RHA® Redensity 2 injection sites. RHA® Redensity 2 should be used with caution in patients who are using substances that can prolong bleeding (such as thrombolytics, anticoagulants, or inhibitors of platelet aggregation).
- Injection of RHA® Redensity 2 into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with RHA® Redensity 2, there is a possible risk of eliciting an in"ammatory reaction at the implant site. This also applies if RHA® Redensity is administered before the skin has healed completely after such a procedure.
- RHA® Redensity is to be used as supplied. Modi!cation or use of the product outside the Instructions for Use may adversely impact the sterility, safety, homogeneity, or performance of the product.
- RHA® Redensity 2 is packaged for single-use. Do not reuse a syringe after treatment. Do not re-sterilize.
- Do not use if package is opened or damaged. The sterility of the product is not guaranteed in the case of failure to comply with this precaution. Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer-lock and needle hub connection.
- RHA® Redensity 2 is a clear, colorless gel without particulates. In the event the contents of a syringe show signs of separation and/or appears cloudy, do not use the syringe; contact Revance Therapeutics, Inc. 877-3REVNOW (877-373-8669)
Adverse Experiences
1. Clinical Evaluation of RHA® Redensity 2
A multicenter, controlled, randomized, blinded, No-Treatment control, prospective clinical study compared the safety and effectiveness of RHA® Redensity versus a No-Treatment control for the treatment of moderate to severe dynamic perioral rhytids. The expected signs and symptoms that occur following the injection of a hyaluronic acid-based dermal !ller (i.e., Common Treatment Responses; CTR) were individually assessed by subjects in a preprinted 14-day diary after each injection. CTRs are commonly expected injection site responses which are temporally associated with injection of a dermal !ller. Events like redness, swelling, pain, bruising, tenderness, and lumps and bumps are examples of expected CTRs. Severe CTRs, or those lasting longer than 14 days or present on the last day of the subject diary, were evaluated for conversion to an adverse event. Subjects were asked to rate each CTR as None, Mild, Moderate or Severe:
- Mild: Little discomfort, no effect on daily activities, no medication or make-up required
- Moderate: some discomfort, some effect on daily activities, possibly medication or make-up required
- Severe: Great discomfort, daily activities compromised, very likely medication or make-up required CTRs by severity and duration are presented respectively, in Table 1 and Table 2.
- The most frequent CTRs were bruising, swelling, redness, !rmness, lumps/bumps and tenderness.
- More than 76% of the CTRs had resolved by Day 7.
- Nearly 90% of CTRs had resolved by Day 14 without treatment.
- Other than lumps/bumps, each type of CTR that was present on the last day of the 14-Day diary was present in less than 10% of subjects.
- For nearly all CTRs (more than 92%), the maximal severity reported was “Mild” or “Moderate”.
- Less than 6% of each CTR was reported as “Severe” by the subjects except for bruising (12%).
- When bruising persisted to the last day of the diary, all were deemed “Mild” by the treating investigator except 3 that were rated at “Moderate”.
None were “Severe”. More than 90% of Bruises had resolved by end of 14-day diary.
Directions For Assembly
Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual !eld testing. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
- ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines
- identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal !ller injection
- conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system de!cits.
Assembly Of Needle To Syringe
1. Remove the stopper from the syringe by pulling it off.
2. Insert the screw thread of the needle !rmly into the syringe end-piece.
3. Screw the needle clockwise, while maintaining slight pressure.
4. Continue screwing until the edge of the cap of the needle contacts the body of the syringe. There must be no space between these two parts. Failure to follow this instruction means that the needle could be ejected and/or leak at the Luer-lock.
5. Remove the needle’s protective cap by pulling it !rmly with one hand while holding the body of the syringe with the other.
Pre-Treatment Guidlines
- Prior to treatment, the patient should avoid taking medications or supplements which thin the blood (e.g., aspirin, nonsteroidal antiin"ammatory medications, St. John’s Wort, high doses of Vitamin E supplements, anti-coagulants) as these agents may increase bruising and bleeding at the injection site.
- Before starting treatment, a complete medical history should be taken from the patient and the patient should be counseled on appropriate indications, risks, and should be informed about the expected treatment results, and expected responses. The patient should be advised of the necessary precautions before commencing the procedure.
- Prior to treatment with RHA® Redensity 2 the patient should be assessed for appropriate anesthetic treatment for managing comfort (e.g., topical anesthetic, local or nerve block). The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
- Sterile gloves are recommended while injecting RHA® Redensity 2.
- Before injecting, prime the needle by carefully pressing the syringe plunger until a small droplet of the gel is visible at the tip of the needle.
Treatment Procedures
A patient information brochure is available on request, or via the website www.revance.com. It is recommended that the following information be shared with patients:
- Patients should be advised not to wear make-up during 12 hours following injection.
- Patient should be advised not to take high-dose Vitamin E, aspirin, anti-in"ammatories or anti-coagulants during the week prior to the injection. Patients must not discontinue such treatment without talking with their prescribing physician.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures (e.g. cold weather, sauna) at least within the !rst 24 hours, or until initial swelling and redness has resolved. Exposure to any of the above may cause/ exacerbate and/or extend the duration of temporary redness, swelling, and/or itching at the treatment sites.
- Patients should notify the injector if any of the following occurs: - Changes in vision - Unusual pain during or shortly after treatment
- Signi!cant pain away from the injection site
- Signs of a stroke - Any redness and/or visible swelling that lasts for more than a week
- Any side effect other than those described above or that occur weeks or months after injection - Adverse reactions should be reported to Revance Therapeutics, Inc at 877-3REV-NOW (877-373-8669) and to [email protected].
Injection Technique
• RHA® Redensity 2 can be administered by using a thin gauge needle (30 G x ½”) and with a number of different techniques that depend on the injector’s experience and preference, and patient characteristics.
A. Preclinical testing between the following needles brands (TSK HPC, TSK PRC, Terumo TW, Terumo ETW) and the syringe has con!rmed that the interoperability and compatibility is reliable and safe. Serial puncture: consists of multiple injections, evenly and closely spaced perpendicular to the lines. This technique is considered to be more precise, but may result in more discomfort for the patient due to the number of punctures.
B. Linear threading: the needle is fully introduced in the wrinkle or the fold, and the product is injected along the line, as a “thread”, while withdrawing (retrograde) or pushing (antegrade) the needle.
C. Fanning technique: the needle is introduced as for the Linear threading technique, and the product is injected along several closely spaced lines, by changing the direction of the needle, all using the same puncture site (the needle is not withdrawn)
• RHA® Redensity 2 is injected slowly into the dermis. If the injection is made too deeply, i.e. into subcutaneous tissue, the correction may not be as expected. It is possible to tell when an injection is being made too deeply because subcutaneous tissue, unlike the dermis, does not offer any resistance to product injection, the injected product may not be visible as a raised elevation on the skin and correction of the lines may not be achieved.
• The injection should be stopped before withdrawing the needle from the skin, to prevent product from leaking but, or product misplacement (too super!cially in the skin).
• The volume to be injected depends on the correction to be performed, but it is important to not overcorrect. Based on the US clinical study, patients should be limited to 6.0 mL per patient per treatment session in perioral rhytids. The safety of injecting greater amounts has not been established.
• Any blanching appearing through the vascular "ow may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
• If the perioral lines need further treatment with RHA® Redensity 2, the same procedure should be repeated until a satisfactory result is obtained.
Sterile Needles
- After use, needles are potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical sharp devices (e.g. discard uncapped needles in approved sharps containers).
- Obtain prompt medical attention if injury with used needle occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not recap needles. Recapping by hand is a hazardous practice and should be avoided.
- RHA® Redensity 2 is provided with 2 needles that do not contain engineered injury protection. Administration of RHA® Redensity 2 requires direct visualization and complete and gradual insertion of the needle making engineered protection devices not feasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is RHA® 2?
RHA® 2 is an injectable gel (also called a dermal filler) used to treat facial wrinkles and folds. It is injected in the moving (dynamic) area of the face especially between the nose and corners of the mouth (nasolabial folds) (see Figure 1). It is approved for use in adults over 22 years of age. RHA® 2 is produced with hyaluronic acid (HA), using an advanced technology to obtain a soft and long lasting injectable gel to smooth facial wrinkles and folds. The HA of the gel is made from a non-animal source. RHA® 2 contains a small amount of an anesthetic medicine (lidocaine), to help reduce discomfort during injection. Hyaluronic acid (HA) is a naturally occurring substance found in the human body. Your body’s own HA helps maintain the skin’s structure and its natural feel.
How does it work?
RHA® 2 is injected into the skin with an ultrafine needle to plump the skin to fill in and smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth. This smoothing effect has been shown to last 12 months in 85% of the patients (53 out of 62 patients) and lasted 15 months in 81% of the patients (38 out of 47 patients).
RHA® 2 is not a permanent gel. It slowly goes away as the body absorbs the gel. The smoothing and plumping effect will gradually disappear.
Safety
Are there precautions that I should discuss with my doctor?
The following are important treatment considerations that you should discuss with your doctor. These hazards, if not avoided, could result in unsatisfactory results or complications.
- Tell your doctor if you are under 22 years of age. RHA® 2 has not been studied in people younger than 22 and the effects are not known.
- Tell your doctor if you are pregnant (or plan to be) or breastfeeding. RHA® 2 has not been studied in women who were pregnant or breastfeeding and the effects are not known.
- Tell your doctor if you are taking medicine that reduces your body’s ability to fight infection (immunosuppressive therapy). Taking this type of medicine may increase the risk of infection following the injection of RHA® 2 or other dermal fillers.
- Be sure to tell your injecting doctor if you are using “blood thinners” (anticoagulants) or any other medications that affect bleeding. Do not stop taking them until you speak with the doctor who prescribed them for you. Tell your prescribing doctor that you are considering having your wrinkles treated with RHA® 2. These blood thinning medications may cause increased bleeding and/or bruising in the treated area.
- Tell your doctor if you have a history of cold sores (herpes). Any injection, including RHA® 2, in the general area may trigger a recurrence of your cold sores (herpes).
- Tell your doctor if you have an injury, or other skin condition near the injection site(s). Injection of a dermal filler in this situation may lead to a worsening of your condition or infection. You may have to wait until you are completely healed before using RHA® 2.
- Tell your doctor if you have ever developed a thick tough scar (keloid) or had problems with skin discoloration. It is possible that injection of any dermal filler, including RHA® 2, may make the skin thicker and change color. However, when RHA® 2 was studied in patients with different skin tones (pale to dark), there were no reports of this happening.
- Tell your doctor if you have already been injected with dermal fillers in the same area, as the one(s) you are about to be treated for. This
information helps your doctor decide when and whether you should get treatment with RHA® 2. - Tell your doctor if you have recently had (within 6 months), or are considering, laser treatment, chemical peeling or any other facial procedure. Use of RHA® 2 with these skin treatments may lead to an increased severity of the common treatment reactions such as redness, swelling, heat or pain in the area.
- You should not take Vitamin E, aspirin, or antiinflammatories during the week prior to the injection. Taking these medications can thin your blood and may result in increased bleeding and/or more bruising in the treated area.
If you have any additional questions about any topic in this section, please discuss further with your doctor.
Troubleshooting
Call your doctor if you have any questions or concerns after your procedure.
Call your doctor immediately if you have:
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
- Changes in your vision
- Pain which increases after your treatment
- Significant pain away from the injection site
- White appearance of the skin
- Any treatment reaction other than bruising, firmness, swelling, pain, tenderness, redness, lumps/bumps, change in skin color or itching, which occurs in the first two weeks
- Any treatment reaction in the treated area, including lump or hardening under the skin, that appears weeks or months after your injection The following are common reactions often seen after treatment with dermal fillers. They usually go away within 2 weeks. If you are concerned, or if they last more than 2 weeks, call your doctor:
• Bruising
• Firmness
• Swelling
• Pain
• Tenderness
• Redness
• Lumps/bumps
• Change in skin color
• Itching
Administration
-
Post Marketing Surveillance
The following adverse events were reported as part of post-marketing surveillance on the use of RHA® 2 Redensity outside the United States with a prevalence equal or superior to 1 occurrence for 100,000 syringes: edema, injection site masses (lumps and bumps), in"ammatory nodules (papules), skin swelling, skin induration, vascular skin disorder (such as vessel compression/occlusion), pain, ecchymosis, and in"ammatory reaction. Additionally, other less frequent adverse reactions have also been reported, and include dermal !ller overcorrection, allergic reaction, product misplacement, skin discoloration, skin necrosis, erythema, granuloma, injection site movement impairment/paraesthesia, skin atrophy and tenderness. Delayed-onset in"ammation near the site of dermal !ller injections is one of the known adverse events associated with dermal !llers. Cases of delayed-onset in"ammation have been reported to occur at the dermal !ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in"ammation was responsive to treatment or resolved on its own.
In many cases the symptoms resolved without any treatment. Reported treatments and procedures included the use of (in alphabetical order): analgesics, antibiotics, anti-histamines, anti-in"ammatories, anti-viral, implant dissolution (hyaluronidase), drainage, excision, incision, massage, and vasodilators
Post-treatment Checklist
- When the injection is completed, the treated site may be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area !rmly between your !ngers or against an underlying area to obtain optimal results.
- If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period (e.g., 5-10 minutes). Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
- After use, syringes may be potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical biohazard devices. Obtain prompt medical attention if injury occurs.
User Assistance Information
In case you have any further questions, please contact Revance Therapeutics, Inc. at 877-3REV-NOW (877-373-8669). www.revance.com RHA® is a registered trademark of TEOXANE S.A. TEOXANE S.A. Rue de Lyon 105 CH 1203 Geneva (Switzerland)
RHA 3
PATIENT INSTRUCTION
PACKAGE INSERT
Description
RHA® Redensity 3 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogeneous and biodegradable gel implant of both crosslinked and non-crosslinked hyaluronic acid. It is produced with sodium Hyaluronic Acid (NaHA) with a concentration of 15 mg/g obtained from bacterial fermentation using the streptococcus equi bacterial strain, crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® Redensity 3 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.
Indication
RHA® Redensity 3 is indicated for injection into the dermis and super!cial dermis of the face, for the correction of moderate to severe dynamic perioral rhytids, in adults aged 22 years or older.
How Supplied
RHA® Redensity 3 is supplied in individual blisters containing a 1 mL treatment syringe with two 30 G x ½” needles as indicated on the carton. The content of the syringe is sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged. Each syringe is packaged into a blister with two unique device identi!er traceability labels.
Self Life and Storage
RHA® Redensity 3 must be used prior to the expiration date printed on the package.
Store at room temperature (up to 25°C/77°F). Do not expose to direct sunlight. DO NOT FREEZE.
Do not store partially used syringes.
Contraindications
- RHA® Redensity 3 is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- RHA® Redensity 3 contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- RHA® Redensity 3 should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
- RHA® Redensity 3 should not be used in patients with bleeding disorders.
Warnings
- RHA® Redensity 3 must not be injected into blood vessels. Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue !llers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue !llers in the face have been reported and include temporary or permanent vision impairment or blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Product use at speci!c sites in which an active in"ammatory process (skin eruptions such as cysts, pimples, rashes, or hives), infection or skin injury is present should be deferred until the underlying process has been controlled.
- Treatment site reactions consist mainly of short-term in"ammatory symptoms (e.g., swelling, redness, tenderness, or pain) and generally resolve within 14 days. Refer to the ADVERSE EXPERIENCES section for details.
- In"ammatory reaction, anaphylactic reaction, edema, implant migration, acne, blisters, scarring, papules and delayed onset of granulomas have been reported following the use of dermal !llers.
Precautions
- In order to minimize the risks of potential complications, this product should only be used by experienced health care practitioners who have appropriate training in !ller injection techniques, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- The safety and effectiveness for the treatment of anatomic regions other than those described in the INTENDED USE / INDICATIONS section have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal !ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- The safety for use in sites in the presence of other implants (including permanent implants) has not been studied.
- The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years of age has not been established.
- RHA® Redensity 3 should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at RHA® Redensity 3 injection sites. RHA® Redensity 3 should be used with caution in patients who are using substances that can prolong bleeding (such as thrombolytics, anticoagulants, or inhibitors of platelet aggregation).
- Injection of RHA® Redensity 3 into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with RHA® Redensity 3, there is a possible risk of eliciting an in"ammatory reaction at the implant site. This also applies if RHA® Redensity 3 is administered before the skin has healed completely after such a procedure.
- RHA® Redensity 3 is to be used as supplied. Modi!cation or use of the product outside the Instructions for Use may adversely impact the sterility, safety, homogeneity, or performance of the product.
- RHA® Redensity 3 is packaged for single-use. Do not reuse a syringe after treatment. Do not re-sterilize.
- Do not use if package is opened or damaged. The sterility of the product is not guaranteed in the case of failure to comply with this precaution. Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer-lock and needle hub connection.
- RHA® Redensity 3 is a clear, colorless gel without particulates. In the event the contents of a syringe show signs of separation and/or appears cloudy, do not use the syringe; contact Revance Therapeutics, Inc. 877-3REVNOW (877-373-8669)
Adverse Experiences
1. Clinical Evaluation of RHA® Redensity 3
A multicenter, controlled, randomized, blinded, No-Treatment control, prospective clinical study compared the safety and effectiveness of RHA® Redensity 3 versus a No-Treatment control for the treatment of moderate to severe dynamic perioral rhytids. The expected signs and symptoms that occur following the injection of a hyaluronic acid-based dermal !ller (i.e., Common Treatment Responses; CTR) were individually assessed by subjects in a preprinted 14-day diary after each injection. CTRs are commonly expected injection site responses which are temporally associated with injection of a dermal !ller. Events like redness, swelling, pain, bruising, tenderness, and lumps and bumps are examples of expected CTRs. Severe CTRs, or those lasting longer than 14 days or present on the last day of the subject diary, were evaluated for conversion to an adverse event. Subjects were asked to rate each CTR as None, Mild, Moderate or Severe:
- Mild: Little discomfort, no effect on daily activities, no medication or make-up required
- Moderate: some discomfort, some effect on daily activities, possibly medication or make-up required
- Severe: Great discomfort, daily activities compromised, very likely medication or make-up required CTRs by severity and duration are presented respectively, in Table 1 and Table 2.
- The most frequent CTRs were bruising, swelling, redness, !rmness, lumps/bumps and tenderness.
- More than 76% of the CTRs had resolved by Day 7.
- Nearly 90% of CTRs had resolved by Day 14 without treatment.
- Other than lumps/bumps, each type of CTR that was present on the last day of the 14-Day diary was present in less than 10% of subjects.
- For nearly all CTRs (more than 92%), the maximal severity reported was “Mild” or “Moderate”.
- Less than 6% of each CTR was reported as “Severe” by the subjects except for bruising (12%).
- When bruising persisted to the last day of the diary, all were deemed “Mild” by the treating investigator except 3 that were rated at “Moderate”.
None were “Severe”. More than 90% of Bruises had resolved by end of 14-day diary.
Directions For Assembly
Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual !eld testing. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
- ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines
- identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal !ller injection
- conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system de!cits.
Assembly Of Needle To Syringe
1. Remove the stopper from the syringe by pulling it off.
2. Insert the screw thread of the needle !rmly into the syringe end-piece.
3. Screw the needle clockwise, while maintaining slight pressure.
4. Continue screwing until the edge of the cap of the needle contacts the body of the syringe. There must be no space between these two parts. Failure to follow this instruction means that the needle could be ejected and/or leak at the Luer-lock.
5. Remove the needle’s protective cap by pulling it !rmly with one hand while holding the body of the syringe with the other.
Pre-Treatment Guidlines
- Prior to treatment, the patient should avoid taking medications or supplements which thin the blood (e.g., aspirin, nonsteroidal antiin"ammatory medications, St. John’s Wort, high doses of Vitamin E supplements, anti-coagulants) as these agents may increase bruising and bleeding at the injection site.
- Before starting treatment, a complete medical history should be taken from the patient and the patient should be counseled on appropriate indications, risks, and should be informed about the expected treatment results, and expected responses. The patient should be advised of the necessary precautions before commencing the procedure.
- Prior to treatment with RHA® Redensity 3 the patient should be assessed for appropriate anesthetic treatment for managing comfort (e.g., topical anesthetic, local or nerve block). The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
- Sterile gloves are recommended while injecting RHA® Redensity.
- Before injecting, prime the needle by carefully pressing the syringe plunger until a small droplet of the gel is visible at the tip of the needle. INJECTION TECHNIQUES
Treatment Procedures
A patient information brochure is available on request, or via the website www.revance.com. It is recommended that the following information be shared with patients:
- Patients should be advised not to wear make-up during 12 hours following injection.
- Patient should be advised not to take high-dose Vitamin E, aspirin, anti-in"ammatories or anti-coagulants during the week prior to the injection. Patients must not discontinue such treatment without talking with their prescribing physician.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures (e.g. cold weather, sauna) at least within the !rst 24 hours, or until initial swelling and redness has resolved. Exposure to any of the above may cause/ exacerbate and/or extend the duration of temporary redness, swelling, and/or itching at the treatment sites.
- Patients should notify the injector if any of the following occurs: - Changes in vision - Unusual pain during or shortly after treatment
- Signi!cant pain away from the injection site
- Signs of a stroke - Any redness and/or visible swelling that lasts for more than a week
- Any side effect other than those described above or that occur weeks or months after injection - Adverse reactions should be reported to Revance Therapeutics, Inc at 877-3REV-NOW (877-373-8669) and to [email protected].
Injection Technique
• RHA® Redensity 3 can be administered by using a thin gauge needle (30 G x ½”) and with a number of different techniques that depend on the injector’s experience and preference, and patient characteristics.
A. Preclinical testing between the following needles brands (TSK HPC, TSK PRC, Terumo TW, Terumo ETW) and the syringe has con!rmed that the interoperability and compatibility is reliable and safe. Serial puncture: consists of multiple injections, evenly and closely spaced perpendicular to the lines. This technique is considered to be more precise, but may result in more discomfort for the patient due to the number of punctures.
B. Linear threading: the needle is fully introduced in the wrinkle or the fold, and the product is injected along the line, as a “thread”, while withdrawing (retrograde) or pushing (antegrade) the needle.
C. Fanning technique: the needle is introduced as for the Linear threading technique, and the product is injected along several closely spaced lines, by changing the direction of the needle, all using the same puncture site (the needle is not withdrawn)
• RHA® Redensity 3 is injected slowly into the dermis. If the injection is made too deeply, i.e. into subcutaneous tissue, the correction may not be as expected. It is possible to tell when an injection is being made too deeply because subcutaneous tissue, unlike the dermis, does not offer any resistance to product injection, the injected product may not be visible as a raised elevation on the skin and correction of the lines may not be achieved.
• The injection should be stopped before withdrawing the needle from the skin, to prevent product from leaking but, or product misplacement (too super!cially in the skin).
• The volume to be injected depends on the correction to be performed, but it is important to not overcorrect. Based on the US clinical study, patients should be limited to 6.0 mL per patient per treatment session in perioral rhytids. The safety of injecting greater amounts has not been established.
• Any blanching appearing through the vascular "ow may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
• If the perioral lines need further treatment with RHA® Redensity 3, the same procedure should be repeated until a satisfactory result is obtained.
Sterile Needles
- After use, needles are potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical sharp devices (e.g. discard uncapped needles in approved sharps containers).
- Obtain prompt medical attention if injury with used needle occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not recap needles. Recapping by hand is a hazardous practice and should be avoided.
- RHA® Redensity 3 is provided with 2 needles that do not contain engineered injury protection. Administration of RHA® Redensity 3 requires direct visualization and complete and gradual insertion of the needle making engineered protection devices not feasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is RHA® 3?
RHA® 3 is an injectable gel (also called a dermal filler) used to treat facial wrinkles and folds. It is injected in the moving (dynamic) area of the face especially between the nose and corners of the mouth (nasolabial folds) (see Figure 1). It is approved for use in adults over 22 years of age. RHA® 3 is produced with hyaluronic acid (HA), using an advanced technology to obtain a soft and long lasting injectable gel to smooth facial wrinkles and folds. The HA of the gel is made from a non-animal source. RHA® 3 contains a small amount of an anesthetic medicine (lidocaine), to help reduce discomfort during injection. Hyaluronic acid (HA) is a naturally occurring substance found in the human body. Your body’s own HA helps maintain the skin’s structure and its natural feel.
How does it work?
RHA® 3 is injected into the skin with an ultrafine needle to plump the skin to fill in and smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth. This smoothing effect has been shown to last 12 months in 85% of the patients (53 out of 62 patients) and lasted 15 months in 81% of the patients (38 out of 47 patients).
RHA® 3 is not a permanent gel. It slowly goes away as the body absorbs the gel. The smoothing and plumping effect will gradually disappear.
Safety
Are there precautions that I should discuss with my doctor?
The following are important treatment considerations that you should discuss with your doctor. These hazards, if not avoided, could result in unsatisfactory results or complications.
- Tell your doctor if you are under 22 years of age. RHA® 3 has not been studied in people younger than 22 and the effects are not known.
- Tell your doctor if you are pregnant (or plan to be) or breastfeeding. RHA® 3 has not been studied in women who were pregnant or breastfeeding and the effects are not known.
- Tell your doctor if you are taking medicine that reduces your body’s ability to fight infection (immunosuppressive therapy). Taking this type of medicine may increase the risk of infection following the injection of RHA® 3 or other dermal fillers.
- Be sure to tell your injecting doctor if you are using “blood thinners” (anticoagulants) or any other medications that affect bleeding. Do not stop taking them until you speak with the doctor who prescribed them for you. Tell your prescribing doctor that you are considering having your wrinkles treated with RHA® 3. These blood thinning medications may cause increased bleeding and/or bruising in the treated area.
- Tell your doctor if you have a history of cold sores (herpes). Any injection, including RHA® 3, in the general area may trigger a recurrence of your cold sores (herpes).
- Tell your doctor if you have an injury, or other skin condition near the injection site(s). Injection of a dermal filler in this situation may lead to a worsening of your condition or infection. You may have to wait until you are completely healed before using RHA® 3.
- Tell your doctor if you have ever developed a thick tough scar (keloid) or had problems with skin discoloration. It is possible that injection of any dermal filler, including RHA® 3, may make the skin thicker and change color. However, when RHA® 3 was studied in patients with different skin tones (pale to dark), there were no reports of this happening.
- Tell your doctor if you have already been injected with dermal fillers in the same area, as the one(s) you are about to be treated for. This
information helps your doctor decide when and whether you should get treatment with RHA® 3. - Tell your doctor if you have recently had (within 6 months), or are considering, laser treatment, chemical peeling or any other facial procedure. Use of RHA® 3 with these skin treatments may lead to an increased severity of the common treatment reactions such as redness, swelling, heat or pain in the area.
- You should not take Vitamin E, aspirin, or antiinflammatories during the week prior to the injection. Taking these medications can thin your blood and may result in increased bleeding and/or more bruising in the treated area.
If you have any additional questions about any topic in this section, please discuss further with your doctor.
Troubleshooting
Call your doctor if you have any questions or concerns after your procedure.
Call your doctor immediately if you have:
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
- Changes in your vision
- Pain which increases after your treatment
- Significant pain away from the injection site
- White appearance of the skin
- Any treatment reaction other than bruising, firmness, swelling, pain, tenderness, redness, lumps/bumps, change in skin color or itching, which occurs in the first two weeks
- Any treatment reaction in the treated area, including lump or hardening under the skin, that appears weeks or months after your injection The following are common reactions often seen after treatment with dermal fillers. They usually go away within 2 weeks. If you are concerned, or if they last more than 2 weeks, call your doctor:
• Bruising
• Firmness
• Swelling
• Pain
• Tenderness
• Redness
• Lumps/bumps
• Change in skin color
• Itching
Administration
-
Post Marketing Surveillance
The following adverse events were reported as part of post-marketing surveillance on the use of RHA® Redensity 3 outside the United States with a prevalence equal or superior to 1 occurrence for 100,000 syringes: edema, injection site masses (lumps and bumps), in"ammatory nodules (papules), skin swelling, skin induration, vascular skin disorder (such as vessel compression/occlusion), pain, ecchymosis, and in"ammatory reaction. Additionally, other less frequent adverse reactions have also been reported, and include dermal !ller overcorrection, allergic reaction, product misplacement, skin discoloration, skin necrosis, erythema, granuloma, injection site movement impairment/paraesthesia, skin atrophy and tenderness. Delayed-onset in"ammation near the site of dermal !ller injections is one of the known adverse events associated with dermal !llers. Cases of delayed-onset in"ammation have been reported to occur at the dermal !ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in"ammation was responsive to treatment or resolved on its own.
In many cases the symptoms resolved without any treatment. Reported treatments and procedures included the use of (in alphabetical order): analgesics, antibiotics, anti-histamines, anti-in"ammatories, anti-viral, implant dissolution (hyaluronidase), drainage, excision, incision, massage, and vasodilators
Post-treatment Checklist
- When the injection is completed, the treated site may be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area !rmly between your !ngers or against an underlying area to obtain optimal results.
- If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period (e.g., 5-10 minutes). Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
- After use, syringes may be potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical biohazard devices. Obtain prompt medical attention if injury occurs.
User Assistance Information
In case you have any further questions, please contact Revance Therapeutics, Inc. at 877-3REV-NOW (877-373-8669). www.revance.com RHA® is a registered trademark of TEOXANE S.A. TEOXANE S.A. Rue de Lyon 105 CH 1203 Geneva (Switzerland)
RHA 4
PATIENT INSTRUCTION
PACKAGE INSERT
Description
RHA® Redensity 4 is a viscoelastic, sterile, non-pyrogenic, clear, colorless, homogeneous and biodegradable gel implant of both crosslinked and non-crosslinked hyaluronic acid. It is produced with sodium Hyaluronic Acid (NaHA) with a concentration of 15 mg/g obtained from bacterial fermentation using the streptococcus equi bacterial strain, crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and reconstituted in a physiological buffer (pH 7.3). RHA® Redensity 4 also contains 0.3% lidocaine hydrochloride to reduce pain on injection.
Indication
RHA® Redensity 4 is indicated for injection into the dermis and super!cial dermis of the face, for the correction of moderate to severe dynamic perioral rhytids, in adults aged 22 years or older.
How Supplied
RHA® Redensity 4 is supplied in individual blisters containing a 1 mL treatment syringe with two 30 G x ½” needles as indicated on the carton. The content of the syringe is sterile and non-pyrogenic. Do not resterilize. Do not use if package is opened or damaged. Each syringe is packaged into a blister with two unique device identi!er traceability labels.
Self Life and Storage
RHA® Redensity 4 must be used prior to the expiration date printed on the package.
Store at room temperature (up to 25°C/77°F). Do not expose to direct sunlight. DO NOT FREEZE.
Do not store partially used syringes.
Contraindications
- RHA® Redensity 4 is contraindicated for patients with severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies.
- RHA® Redensity 4 contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- RHA® Redensity 4 should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
- RHA® Redensity 4 should not be used in patients with bleeding disorders.
Warnings
- RHA® Redensity 4 must not be injected into blood vessels. Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue !llers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue !llers in the face have been reported and include temporary or permanent vision impairment or blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Product use at speci!c sites in which an active in"ammatory process (skin eruptions such as cysts, pimples, rashes, or hives), infection or skin injury is present should be deferred until the underlying process has been controlled.
- Treatment site reactions consist mainly of short-term in"ammatory symptoms (e.g., swelling, redness, tenderness, or pain) and generally resolve within 14 days. Refer to the ADVERSE EXPERIENCES section for details.
- In"ammatory reaction, anaphylactic reaction, edema, implant migration, acne, blisters, scarring, papules and delayed onset of granulomas have been reported following the use of dermal !llers.
Precautions
- In order to minimize the risks of potential complications, this product should only be used by experienced health care practitioners who have appropriate training in !ller injection techniques, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
- The safety and effectiveness for the treatment of anatomic regions other than those described in the INTENDED USE / INDICATIONS section have not been established in controlled clinical studies.
- As with all transcutaneous procedures, dermal !ller implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied.
- The safety for use in sites in the presence of other implants (including permanent implants) has not been studied.
- The safety for use during pregnancy, in breastfeeding females, and in patients under 22 years of age has not been established.
- RHA® Redensity 4 should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at RHA® Redensity 4 injection sites. RHA® Redensity 4 should be used with caution in patients who are using substances that can prolong bleeding (such as thrombolytics, anticoagulants, or inhibitors of platelet aggregation).
- Injection of RHA® Redensity 4 into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with RHA® Redensity 4, there is a possible risk of eliciting an in""ammatory reaction at the implant site. This also applies if RHA® Redensity 4 is administered before the skin has healed completely after such a procedure.
- RHA® Redensity 4 is to be used as supplied. Modi!cation or use of the product outside the Instructions for Use may adversely impact the sterility, safety, homogeneity, or performance of the product.
- RHA® Redensity 4 is packaged for single-use. Do not reuse a syringe after treatment. Do not re-sterilize.
- Do not use if package is opened or damaged. The sterility of the product is not guaranteed in the case of failure to comply with this precaution. Failure to comply with the needle attachment instructions could result in needle disengagement and/or product leakage at the Luer-lock and needle hub connection.
- RHA® Redensity 4 is a clear, colorless gel without particulates. In the event the contents of a syringe show signs of separation and/or appears cloudy, do not use the syringe; contact Revance Therapeutics, Inc. 877-3REVNOW (877-373-8669)"
Adverse Experiences
1. Clinical Evaluation of RHA® Redensity 4
A multicenter, controlled, randomized, blinded, No-Treatment control, prospective clinical study compared the safety and effectiveness of RHA® Redensity 4 versus a No-Treatment control for the treatment of moderate to severe dynamic perioral rhytids. The expected signs and symptoms that occur following the injection of a hyaluronic acid-based dermal !ller (i.e., Common Treatment Responses; CTR) were individually assessed by subjects in a preprinted 14-day diary after each injection. CTRs are commonly expected injection site responses which are temporally associated with injection of a dermal !ller. Events like redness, swelling, pain, bruising, tenderness, and lumps and bumps are examples of expected CTRs. Severe CTRs, or those lasting longer than 14 days or present on the last day of the subject diary, were evaluated for conversion to an adverse event. Subjects were asked to rate each CTR as None, Mild, Moderate or Severe:
- Mild: Little discomfort, no effect on daily activities, no medication or make-up required
- Moderate: some discomfort, some effect on daily activities, possibly medication or make-up required
- Severe: Great discomfort, daily activities compromised, very likely medication or make-up required CTRs by severity and duration are presented respectively, in Table 1 and Table 2.
- The most frequent CTRs were bruising, swelling, redness, !rmness, lumps/bumps and tenderness.
- More than 76% of the CTRs had resolved by Day 7.
- Nearly 90% of CTRs had resolved by Day 14 without treatment.
- Other than lumps/bumps, each type of CTR that was present on the last day of the 14-Day diary was present in less than 10% of subjects.
- For nearly all CTRs (more than 92%), the maximal severity reported was “Mild” or “Moderate”.
- Less than 6% of each CTR was reported as “Severe” by the subjects except for bruising (12%).
- When bruising persisted to the last day of the diary, all were deemed “Mild” by the treating investigator except 3 that were rated at “Moderate”. None were “Severe”. More than 90% of Bruises had resolved by end of 14-day diary.
Directions For Assembly
Before and after treatment, health care practitioners are encouraged to conduct vision assessments, including visual acuity, extraocular motility, and visual !eld testing. Health care practitioners are encouraged to be prepared with the following in the event of an intravascular injection:
- ensuring supplies are immediately available, as recommended by the American Society for Dermatologic Surgery guidelines
- identifying a local ophthalmologist or ophthalmology subspecialist to be available in the event of an ophthalmic adverse event related to a dermal !ller injection
- conducting a basic neurologic examination in the event of an ophthalmic adverse event due to the association of such events with central nervous system de!cits.
Assembly Of Needle To Syringe
1. Remove the stopper from the syringe by pulling it off.
2. Insert the screw thread of the needle !rmly into the syringe end-piece.
3. Screw the needle clockwise, while maintaining slight pressure.
4. Continue screwing until the edge of the cap of the needle contacts the body of the syringe. There must be no space between these two parts. Failure to follow this instruction means that the needle could be ejected and/or leak at the Luer-lock.
5. Remove the needle’s protective cap by pulling it !rmly with one hand while holding the body of the syringe with the other.
Pre-Treatment Guidlines
- Prior to treatment, the patient should avoid taking medications or supplements which thin the blood (e.g., aspirin, nonsteroidal antiin"ammatory medications, St. John’s Wort, high doses of Vitamin E supplements, anti-coagulants) as these agents may increase bruising and bleeding at the injection site.
- Before starting treatment, a complete medical history should be taken from the patient and the patient should be counseled on appropriate indications, risks, and should be informed about the expected treatment results, and expected responses. The patient should be advised of the necessary precautions before commencing the procedure.
- Prior to treatment with RHA® Redensity 4 the patient should be assessed for appropriate anesthetic treatment for managing comfort (e.g., topical anesthetic, local or nerve block). The patient’s face should be washed with soap and water and dried with a clean towel. Cleanse the area to be treated with alcohol or another suitable antiseptic solution.
- Sterile gloves are recommended while injecting RHA® Redensity 4.
- Before injecting, prime the needle by carefully pressing the syringe plunger until a small droplet of the gel is visible at the tip of the needle.
Treatment Procedures
A patient information brochure is available on request, or via the website www.revance.com. It is recommended that the following information be shared with patients:
- Patients should be advised not to wear make-up during 12 hours following injection.
- Patient should be advised not to take high-dose Vitamin E, aspirin, anti-in""ammatories or anti-coagulants during the week prior to the injection. Patients must not discontinue such treatment without talking with their prescribing physician.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme temperatures (e.g. cold weather, sauna) at least within the !rst 24 hours, or until initial swelling and redness has resolved. Exposure to any of the above may cause/ exacerbate and/or extend the duration of temporary redness, swelling, and/or itching at the treatment sites.
- Patients should notify the injector if any of the following occurs: - Changes in vision - Unusual pain during or shortly after treatment
- Signi!cant pain away from the injection site
- Signs of a stroke - Any redness and/or visible swelling that lasts for more than a week
- Any side effect other than those described above or that occur weeks or months after injection - Adverse reactions should be reported to Revance Therapeutics, Inc at 877-3REV-NOW (877-373-8669) and to [email protected].
Injection Technique
- RHA® Redensity 4 can be administered by using a thin gauge needle (30 G x ½”) and with a number of different techniques that depend on the injector’s experience and preference, and patient characteristics.
A. Preclinical testing between the following needles brands (TSK HPC, TSK PRC, Terumo TW, Terumo ETW) and the syringe has con!rmed that the interoperability and compatibility is reliable and safe. Serial puncture: consists of multiple injections, evenly and closely spaced perpendicular to the lines. This technique is considered to be more precise, but may result in more discomfort for the patient due to the number of punctures.
B. Linear threading: the needle is fully introduced in the wrinkle or the fold, and the product is injected along the line, as a “thread”, while withdrawing (retrograde) or pushing (antegrade) the needle.
C. Fanning technique: the needle is introduced as for the Linear threading technique, and the product is injected along several closely spaced lines, by changing the direction of the needle, all using the same puncture site (the needle is not withdrawn)
- RHA® Redensity 4 is injected slowly into the dermis. If the injection is made too deeply, i.e. into subcutaneous tissue, the correction may not be as expected. It is possible to tell when an injection is being made too deeply because subcutaneous tissue, unlike the dermis, does not offer any resistance to product injection, the injected product may not be visible as a raised elevation on the skin and correction of the lines may not be achieved.
- The injection should be stopped before withdrawing the needle from the skin, to prevent product from leaking but, or product misplacement (too super!cially in the skin).
- The volume to be injected depends on the correction to be performed, but it is important to not overcorrect. Based on the US clinical study, patients should be limited to 6.0 mL per patient per treatment session in perioral rhytids. The safety of injecting greater amounts has not been established.
- Any blanching appearing through the vascular "ow may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection. Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
- If the perioral lines need further treatment with RHA® Redensity 4, the same procedure should be repeated until a satisfactory result is obtained.
Sterile Needles
- After use, needles are potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical sharp devices (e.g. discard uncapped needles in approved sharps containers).
- Obtain prompt medical attention if injury with used needle occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not recap needles. Recapping by hand is a hazardous practice and should be avoided.
- RHA® Redensity 4 is provided with 2 needles that do not contain engineered injury protection. Administration of RHA® Redensity 4 requires direct visualization and complete and gradual insertion of the needle making engineered protection devices not feasible. Care should be taken to avoid sharps exposure by proper environmental controls.
PATIENT INSTRUCTION
Frequently Asked Questions
What is RHA® 4?
RHA® 4 is an injectable gel (also called a dermal filler) used to treat facial wrinkles and folds. It is injected in the moving (dynamic) area of the face especially between the nose and corners of the mouth (nasolabial folds) (see Figure 1). It is approved for use in adults over 22 years of age. RHA® 4 is produced with hyaluronic acid (HA), using an advanced technology to obtain a soft and long lasting injectable gel to smooth facial wrinkles and folds. The HA of the gel is made from a non-animal source. RHA® 4 contains a small amount of an anesthetic medicine (lidocaine), to help reduce discomfort during injection. Hyaluronic acid (HA) is a naturally occurring substance found in the human body. Your body’s own HA helps maintain the skin’s structure and its natural feel.
How does it work?
RHA® 4 is injected into the skin with an ultrafine needle to plump the skin to fill in and smooth away wrinkles and folds such as the lines from your nose to the corners of your mouth. This smoothing effect has been shown to last 12 months in 85% of the patients (53 out of 62 patients) and lasted 15 months in 81% of the patients (38 out of 47 patients).
RHA® 4 is not a permanent gel. It slowly goes away as the body absorbs the gel. The smoothing and plumping effect will gradually disappear.
Safety
Are there precautions that I should discuss with my doctor?
The following are important treatment considerations that you should discuss with your doctor. These hazards, if not avoided, could result in unsatisfactory results or complications.
- Tell your doctor if you are under 22 years of age. RHA® 4 has not been studied in people younger than 22 and the effects are not known.
- Tell your doctor if you are pregnant (or plan to be) or breastfeeding. RHA® 4 has not been studied in women who were pregnant or breastfeeding and the effects are not known.
- Tell your doctor if you are taking medicine that reduces your body’s ability to fight infection (immunosuppressive therapy). Taking this type of medicine may increase the risk of infection following the injection of RHA® 4 or other dermal fillers.
- Be sure to tell your injecting doctor if you are using “blood thinners” (anticoagulants) or any other medications that affect bleeding. Do not stop taking them until you speak with the doctor who prescribed them for you. Tell your prescribing doctor that you are considering having your wrinkles treated with RHA® 4. These blood thinning medications may cause increased bleeding and/or bruising in the treated area.
- Tell your doctor if you have a history of cold sores (herpes). Any injection, including RHA® 4, in the general area may trigger a recurrence of your cold sores (herpes).
- Tell your doctor if you have an injury, or other skin condition near the injection site(s). Injection of a dermal filler in this situation may lead to a worsening of your condition or infection. You may have to wait until you are completely healed before using RHA® 4.
- Tell your doctor if you have ever developed a thick tough scar (keloid) or had problems with skin discoloration. It is possible that injection of any dermal filler, including RHA® 4, may make the skin thicker and change color. However, when RHA® 4 was studied in patients with different skin tones (pale to dark), there were no reports of this happening.
- Tell your doctor if you have already been injected with dermal fillers in the same area, as the one(s) you are about to be treated for. This
information helps your doctor decide when and whether you should get treatment with RHA® 4. - Tell your doctor if you have recently had (within 6 months), or are considering, laser treatment, chemical peeling or any other facial procedure. Use of RHA® 4 with these skin treatments may lead to an increased severity of the common treatment reactions such as redness, swelling, heat or pain in the area.
- You should not take Vitamin E, aspirin, or antiinflammatories during the week prior to the injection. Taking these medications can thin your blood and may result in increased bleeding and/or more bruising in the treated area.
If you have any additional questions about any topic in this section, please discuss further with your doctor.
Troubleshooting
Call your doctor if you have any questions or concerns after your procedure.
Call your doctor immediately if you have:
- Signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
- Changes in your vision
- Pain which increases after your treatment
- Significant pain away from the injection site
- White appearance of the skin
- Any treatment reaction other than bruising, firmness, swelling, pain, tenderness, redness, lumps/bumps, change in skin color or itching, which occurs in the first two weeks
- Any treatment reaction in the treated area, including lump or hardening under the skin, that appears weeks or months after your injection The following are common reactions often seen after treatment with dermal fillers. They usually go away within 2 weeks. If you are concerned, or if they last more than 2 weeks, call your doctor:
• Bruising
• Firmness
• Swelling
• Pain
• Tenderness
• Redness
• Lumps/bumps
• Change in skin color
• Itching
Administration
-
Post Marketing Surveillance
The following adverse events were reported as part of post-marketing surveillance on the use of RHA® Redensity 4 outside the United States with a prevalence equal or superior to 1 occurrence for 100,000 syringes: edema, injection site masses (lumps and bumps), in"ammatory nodules (papules), skin swelling, skin induration, vascular skin disorder (such as vessel compression/occlusion), pain, ecchymosis, and in"ammatory reaction. Additionally, other less frequent adverse reactions have also been reported, and include dermal !ller overcorrection, allergic reaction, product misplacement, skin discoloration, skin necrosis, erythema, granuloma, injection site movement impairment/paraesthesia, skin atrophy and tenderness. Delayed-onset in"ammation near the site of dermal !ller injections is one of the known adverse events associated with dermal !llers. Cases of delayed-onset in"ammation have been reported to occur at the dermal !ller treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported in"ammation was responsive to treatment or resolved on its own.
In many cases the symptoms resolved without any treatment. Reported treatments and procedures included the use of (in alphabetical order): analgesics, antibiotics, anti-histamines, anti-in"ammatories, anti-viral, implant dissolution (hyaluronidase), drainage, excision, incision, massage, and vasodilators
Post-treatment Checklist
- When the injection is completed, the treated site may be gently massaged so that it conforms to the contour of the surrounding tissues. If an overcorrection has occurred, massage the area !rmly between your !ngers or against an underlying area to obtain optimal results.
- If the treated area is swollen immediately after the injection, an ice pack can be applied to the site for a short period (e.g., 5-10 minutes). Ice should be used with caution if the area is still numb from anesthetic to avoid thermal injury.
- After use, syringes may be potential biohazards. Follow national, local, or institutional guidelines for use and disposal of medical biohazard devices. Obtain prompt medical attention if injury occurs.
User Assistance Information
In case you have any further questions, please contact Revance Therapeutics, Inc. at 877-3REV-NOW (877-373-8669). www.revance.com RHA® is a registered trademark of TEOXANE S.A. TEOXANE S.A. Rue de Lyon 105 CH 1203 Geneva (Switzerland)
Versa
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Revanesse® Versa™ is manufactured by Prollenium Medical Technologies, and is a biocompatible, sterile, injectable hydrogel based on bioresorbable cross-linked hyaluronan (HA) (22 – 28 mg / mL concentration). The gel is delivered in a pre-filled disposable glass syringe. Each box of Revanesse® Versa™ contains two 1.0 mL or 1.2 mL syringes of Revanesse® Versa™ along with two sterile needles.
Revanesse® Versa™ is injected by qualified, trained doctors into the dermis of patients, using a variety of techniques. The injections place a small portion of the gel beneath a crease or wrinkle in the skin and the augmentation of the tissue produces a smoothing effect on the surface.
Indication
Revanesse® Versa™ is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds, such as nasolabial folds, in adults 22 years of age or more.
How Supplied
-
Self Life and Storage
Expiry is indicated on each individual package. Store between 2°- 25° C, and protect from direct sun light and freezing. Do not use the product beyond the stated expiration date. Confirm that the seal on the box has not been broken and sterility has not been compromised. Confirm that the product has not expired. Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases.
NOTE: The correct injection technique is crucial to treatment success and patient satisfaction. Revanesse® Versa™ should only be injected by a practitioner qualified according to local laws and standards. The graduation on the syringe is not precise and should be used as a guide only. The amount of material to be injected is best determined by visual and tactile assessment by the user
Contraindications
Revanesse® Versa™ is only intended for intradermal use and must not be injected into blood vessels. Implantation of Revanesse® Versa™ into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena.
Revanesse® Versa™ contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
Do not inject Revanesse® Versa™ Versa™ into eye contours. Serious adverse events have been reported related to the use of dermal fillers in the area of the eye.
This product has not been evaluated in pregnant women, or women during lactation, and these individuals should not be treated with Revanesse® Versa™.
Patients who develop hypertrophic scarring or keloid formation should not be treated with Revanesse® Versa™.
Patients with evidence of scars at the intended treatment sites should not be treated with Revanesse® Versa™.
Never use Revanesse® Versa™ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment. People under the age of 22 should not be treated with Revanesse® Versa™.
Patients with acne and / or other inflammatory diseases of the skin should not be treated with Revanesse® Versa™.
Patients with unattainable expectations.
Patients with multiple severe allergies, allergic history including anaphylaxis, atopy, hyaluronic acid products, Streptococcal proteins or have plans to undergo desensitization therapy during treatment with Revanesse® Versa™ should not use the product.
Revanesse® Versa™ should not be used in patients with acute or chronic skin disease in or near the injection sites, or with any infection or unhealed wound of the face. Individuals who are under concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders, coagulation defects or connective tissue disorders should not use this product
Warnings
Confirm that the seal on the box has not been broken and sterility has not been compromised.
Confirm that the product has not expired.
Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases. Revanesse® Versa™ is a prescription product.
Revanesse® Versa™ is a clear colorless gel. If the contents of the syringe are not clear and colorless, or if the glass syringe is compromised, contact Prollenium Medical Technologies immediately at 1-866-353-3017.
Revanesse® Versa™ should not be used in areas that have high vascularity as there is a risk of vascular embolization. There are published reports of dermal filler use in the area of the eye resulting in ocular vessel occlusion (i.e.: blindness).
Avoid the use of Revanesse® Versa™ when there is an active inflammatory process (pimples, hives, rashes, cysts) until the process has resolved.
Injection site reactions (for example: redness, temporary swelling, tenderness or pain) have been observed, and are short term in duration (less than seven days). Any reactions in excess of this anticipated reaction should be reported to your doctor.
All injections / transcutaneous procedures carry the risk of infection. Care must be taken to follow standard precautions for injections. Dermal fillers have an inherent risk of keloid formation and hyperpigmentation at the injection site. Patients historically prone to these conditions should avoid dermal fillers.
If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection.
Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection. Warning: Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction.
Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure.
Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur. In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications. Revanesse® Versa™ should not be mixed with any other products before implantation.
It is imperative that Revanesse® Versa™ patients with adverse inflammatory reactions that persist for more than one week report this immediately to their doctor.
Please contact the company Prollenium Medical Technologies immediately at 1-866-353-3017.
Precautions
Confirm that the seal on the box has not been broken and sterility has not been compromised.
Confirm that the product has not expired.
Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases. Revanesse® Versa™ is a prescription product.
Revanesse® Versa™ is a clear colorless gel. If the contents of the syringe are not clear and colorless, or if the glass syringe is compromised, contact Prollenium Medical Technologies immediately at 1-866-353-3017.
Revanesse® Versa™ should not be used in areas that have high vascularity as there is a risk of vascular embolization. There are published reports of dermal filler use in the area of the eye resulting in ocular vessel occlusion (i.e.: blindness).
Avoid the use of Revanesse® Versa™ when there is an active inflammatory process (pimples, hives, rashes, cysts) until the process has resolved.
Injection site reactions (for example: redness, temporary swelling, tenderness or pain) have been observed, and are short term in duration (less than seven days). Any reactions in excess of this anticipated reaction should be reported to your doctor.
All injections / transcutaneous procedures carry the risk of infection. Care must be taken to follow standard precautions for injections. Dermal fillers have an inherent risk of keloid formation and hyperpigmentation at the injection site. Patients historically prone to these conditions should avoid dermal fillers.
If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion. If normal skin coloring does not return, do not continue with the injection.
Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection. Warning: Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction.
Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure.
Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur. In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications. Revanesse® Versa™ should not be mixed with any other products before implantation.
It is imperative that Revanesse® Versa™ patients with adverse inflammatory reactions that persist for more than one week report this immediately to their doctor.
Please contact the company Prollenium Medical Technologies immediately at 1-866-353-3017.
Adverse Experiences
Patients were treated between 18 May 2015 and 04 April 2016. The database for the initial phase of the study reflected data collected through 03 March 2016 and included 163 patients. T
he database for the retreatment study reflected data collected through 07 September 2016 and included 71 patients. There were 4 investigational sites.
The study was a randomized, multicenter, double blind, split-face study in subjects seeking nasolabial fold (NLF) correction.
Subjects were treated with Revanesse® Versa™ in the NLF on one side of the face and Comparator in the NLF on the other side of the face.
The Comparator used was an FDA-approved crosslinked hyaluronic acid dermal filler which is legally marketed with similar indications for use.
The side of the face for each product was randomly assigned. Randomization followed a 1:1 within-subject Comparator model of augmentation correction of NLFs.
The investigator performing the evaluations and the subject were blinded to the treatment; injections of the study product were performed by an unblinded injecting investigator.
The primary efficacy variable was change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) score (i.e., WSRS at Visit 1 – WSRS at Visit 6).
Summary statistics and 95% confidence interval (CI) were presented for the change scores for each treatment and for the difference in change scores between the two treatments (Comparator minus Test product, i.e., Comparator minus Revanesse® Versa™).
The 95% CI for difference between treatments was constructed assuming a normal distribution of the change scores.
If the upper bound of this 95% CI was less than the pre-specified non inferiority limit of 0.50, the Test product would be claimed to be non-inferior to the Comparator product.
Subjects meeting the inclusion and exclusion criteria were randomized to treatment with Revanesse® Versa™ in the NLF on one side of the face and Comparator in the NLF on the other side of the face. SYM2014-02 Retreatment - Subjects could have open-label retreatment as needed with Revanesse® Versa™ at 6 months if their WSRS scores had returned to baseline, or as needed to achieve optimal correction if their WSRS scores had not returned to baseline, and were followed for a total of 12 months. The study design was appropriate for the indication studied.
Validated methods of data collection, analysis, and evaluation were used. Of the 163 treated subjects, one or more injection-site TEAEs during the study were reported for 114 (69.9%) with Revanesse®Versa™ treatment and 137 (84.0%) with Comparator treatment, and most events were considered by the investigator to\ Table 2: SYM2014-02 Main Study – Most Frequently Occurring Injection Site Treatment-Emergent Adverse Events (TEAEs) by MedDRA Preferred Term for Intent-to-Treat Population Most frequently occurring injection site TEAEs are those that were reported by 5% or more subjects with either treatment.
Counts reflect numbers of subjects reporting one or more injection site TEAEs that map to the MedDRA (version
15.1) system organ class/preferred term.
At each level of summarization (system organ class or preferred term) subjects reporting more than one injection site TEAE are only counted once.
Directions For Assembly
-
Assembly Of Needle To Syringe
NOTE: The correct injection technique is crucial to treatment success and patient satisfaction. Revanesse® Versa™ should only be injected by a practitioner qualified according to local laws and standards. The graduation on the syringe is not precise and should be used as a guide only. The amount of material to be injected is best determined by visual and tactile assessment by the user
Pre-Treatment Guidlines
Your doctor will examine you, and will explain the procedure and the potential risks. You will be asked about your health, your medical history, and the medications you take and have recently taken. You should advise your doctor of any of your concerns before the procedure, and discuss any questions related to the procedure.
Treatment Procedures
The doctor will prepare the area to be treated. There is some pain associated with the injection of the product. You should discuss your concerns about injection related pain with your doctor. The doctor will inject the filler, during which you may experience tenderness or a stinging sensation in the area of the injection. The procedure does not take long, often 15 to 30 minutes.
Injection Technique
-
Sterile Needles
-
PATIENT INSTRUCTION
Frequently Asked Questions
What is Revanesse® Versa™?
Revanesse® Versa™ is hyaluronic acid dermal filler. Hyaluronic acid is a naturally occurring substance that is found within the body. It may be produced by bacteria and purified for use as injectable soft tissue filler in order to correct the appearance of facial wrinkles and creases, (nasolabial folds). The product is approved for use in the U.S. by the Food and Drug Administration for the cosmetic treatment of facial wrinkles and creases.
How does Revanesse® Versa™ work?
Revanesse® Versa™ is an injection into the facial tissue to improve the appearance of facial wrinkles and creases, such as nasolabial folds. The injection results in a smoothing effect. The product is intended for individuals 22 years of age or more seeking correction of their facial wrinkles and creases.
Are there any warnings I should be aware of?
If you have an adverse inflammatory reaction, such as redness, pain and swelling that persist for one week or more after treatment with Revanesse® Versa™, you should report this immediately to your doctor. If you are under the age of 22 you should not be treated with Revanesse® Versa™. Warning: One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
Are there any reasons why I should not (contraindications) receive the Revanesse® Versa™ injection?
You should not be treated with Revanesse® Versa™ if you:
- are pregnant or breastfeeding, as the safety of these products for use during pregnancy, or in women who are breastfeeding, has not been studied
- have a history of hypertrophic scarring or keloid formation
- have evidence of scars at the intended treatment sites
- have acne and / or other inflammatory diseases of the skin, such as rosacea, seborrheic dermatitis, and psoriasis,
- have allergic history including;
- severe allergic reactions (anaphylaxis),
- heightened immune responses to common allergens, especially inhaled allergens and food allergens (atopy),
- allergy to hyaluronic acid products,
- Streptococcal proteins or have plans to undergo administration of graded doses of allergens (desensitization therapy) during treatment with Revanesse® Versa™. - have acute or chronic skin disease, such as seborrheic dermatitis or rosacea, in or near the injection sites, or any infection or unhealed wound of the face
- are under concomitant anticoagulant therapy, antiplatelet therapy, or have a history of bleeding disorders, clotting disorders such as hemophilia or connective tissue disorders such as systemic lupus erythematosus You should never use Revanesse® Versa™ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment, as there is a possible risk of inflammation at the treatment site if these procedures are performed before treatment.
Safety
-
Troubleshooting
If you have any questions about your treatment with Revanesse® Versa™, or do not understand something about dermal filler injections, you should ask your doctor, or his or her staff, to explain. You should feel free to discuss your concerns openly with your doctor in order to better understand your options for treatment of facial wrinkles and creases (nasolabial folds).
Administration
-
Post Marketing Surveillance
Postmarket surveillance for Revanesse® Versa and Revanesse® Versa+ reported the following adverse events (AEs) with 5 or greater instances:swelling, bruising, and lumps for the United States. In some instances, patients reporting these adverse events experienced symptoms that were severe, prompting additional medical evaluation. When required, treatment included massage, cold compresses, analgesics, antibiotics, antihistamines, topical steroids, oral corticosteroids, and enzymatic degradation (with hyaluronidase) of the product.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
Following treatment, a cold compress or ice may be applied for any bruising or swelling at the injection site. You may also gently massage the area with constant pressure for several minutes. The most common side effects include: bruising, redness, swelling, pain, and itching.
You should contact your doctor if you experience redness, itching or pain at the injection site for recommendations for over-the-counter treatment (such as Tylenol, Motrin or Benadryl). Most side effects occur shortly after injection and go away within two weeks. If you experience a reaction that lasts longer than two weeks, or what you think may be a delayed reaction to the product, contact your doctor.
You should seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site (blanching) or any other unexpected symptoms. While rare, unexpected symptoms include unusual pain, vision changes, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, visual changes, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure.
Additional side effects of dermal fillers less commonly reported include: infections, lumps and bumps, discoloration or change in pigmentation. It is rare for patients to have a delayed onset reaction or an infection such as cold sores (herpetic sores).
Rare, but serious risks, of dermal fillers include: scarring, blurred vision, partial vision loss, and blindness if the dermal filler is inadvertently injected into a blood vessel. In occasionally rare cases, there have been reports of unintentional injection of the product into a blood vessel with dermal filler products. It is recommended that doctors take care to avoid injection into blood vessels (especially around the forehead, nose and eye area) for these reasons, allergic reaction that may lead to a severe reaction (anaphylactic shock) that requires emergency medical help.
User Assistance Information
If you require immediate assistance, please contact your health care provider. For further assistance, please contact Prollenium Medical Technologies Inc. at 1-866-353-3017 (24 hours a day).
Versa +
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Revanesse® Versa™+ is manufactured by Prollenium Medical Technologies, and is a biocompatible, sterile, injectable hydrogel based on bioresorbable cross-linked hyaluronan (HA) (22 – 28 mg / mL concentration) containing 0.3% lidocaine. The gel is delivered in a pre-filled disposable glass syringe. Each box of Revanesse® Versa™+ contains two 1.0 mL or 1.2 mL syringes of Revanesse® Versa™+ along with two sterile needles.
Revanesse® Versa™+ is injected by qualified, trained doctors into the dermis of patients, using a variety of techniques. The injections place a small portion of the gel beneath a crease or wrinkle in the skin and the augmentation of the tissue produces a smoothing effect on the surface.
Indication
Revanesse® Versa™+ is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds, such as nasolabial folds, in adults 22 years of age or more
How Supplied
-
Self Life and Storage
Expiry is indicated on each individual package. Store between 2°- 25° C, and protect from direct sun light and freezing. Do not use the product beyond the stated expiration date. Confirm that the seal on the box has not been broken and sterility has not been compromised. Confirm that the product has not expired. Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases.
NOTE: The correct injection technique is crucial to treatment success and patient satisfaction. Revanesse® Versa™+ should only be injected by a practitioner qualified according to local laws and standards. The graduation on the syringe is not precise and should be used as a guide only. The amount of material to be injected is best determined by visual and tactile assessment by the user
Contraindications
Revanesse® Versa™+ is only intended for intradermal use and must not be injected into blood vessels. Implantation of Revanesse® Versa™+ into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena.
Revanesse® Versa™+ contains lidocaine, and is contraindicated for patients with a history of allergies or sensitivities to such material and should not be used in patients with previous hypersensitivity to local anaesthetics of the amide type, such as lidocaine.
Revanesse® Versa™+ contains trace amounts of gram positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
Do not inject Revanesse® Versa™+ into eye contours. Serious adverse events have been reported related to the use of dermal fillers in the area of the eye.
This product has not been evaluated in pregnant women, or women during lactation, and these individuals should not be treated with Revanesse® Versa™+.
Patients who develop hypertrophic scarring or keloid formation should not be treated with Revanesse® Versa™+.
Patients with evidence of scars at the intended treatment sites should not be treated with Revanesse® Versa™+.
Never use Revanesse® Versa™+ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment.
People under the age of 22 should not be treated with Revanesse® Versa™+.
Patients with acne and / or other inflammatory diseases of the skin should not be treated with Revanesse® Versa™+.
Patients with unattainable expectations.
Patients with multiple severe allergies, allergic history including anaphylaxis, atopy, hyaluronic acid products, Streptococca proteins or have plans to undergo desensitization therapy during treatment with Revanesse® Versa™+ should not use the product.
Revanesse® Versa™+ should not be used in patients with acute or chronic skin disease in or near the injection sites, or with any infection or unhealed wound of the face.
Individuals who are under concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders, coagulation defects or connective tissue disorders should not use this product.
Warnings
Confirm that the seal on the box has not been broken and sterility has not been compromised.
Confirm that the product has not expired. Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases.
Revanesse Versa is a prescription product. Revanesse Versa is a clear colorless gel.
If the contents of the syringe are not clear and colorless, or if the glass syringe is compromised, contact Prollenium Medical Technologies immediately at 1-866-353-3017.
Revanesse Versa should not be used in areas that have high vascularity as there is a risk of vascular embolization.
There are published reports of dermal filler use in the area of the eye resulting in ocular vessel occlusion (i.e.: blindness). Avoid the use of Revanesse Versa when there is an active inflammatory process (pimples, hives, rashes, cysts) until the process has resolved.
Injection site reactions (for example: redness, temporary swelling, tenderness or pain) have been observed, and are short term in duration (less than seven days).
Any reactions in excess of this anticipated reaction should be reported to your doctor.
All injections / transcutaneous procedures carry the risk of infection. Care must be taken to follow standard precautions for injections.
Dermal fillers have an inherent risk of keloid formation and hyperpigmentation at the injection site.
Patients historically prone to these conditions should avoid dermal fillers.
If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion.
If normal skin coloring does not return, do not continue with the injection.
Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
Warning: Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction.
Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure.
Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
Revanesse Versa should not be mixed with any other products before implantation.
It is imperative that Revanesse Versa patients with adverse inflammatory reactions that persist for more than one week report this immediately to their doctor.
Please contact the company Prollenium Medical Technologies immediately at 1-866-353-3017.
Precautions
Confirm that the seal on the box has not been broken and sterility has not been compromised.
Confirm that the product has not expired. Product is for single use only; do not re-use. If re-used, there is a risk of infection or transmission of blood borne diseases.
Revanesse Versa is a prescription product. Revanesse Versa is a clear colorless gel.
If the contents of the syringe are not clear and colorless, or if the glass syringe is compromised, contact Prollenium Medical Technologies immediately at 1-866-353-3017.
Revanesse Versa should not be used in areas that have high vascularity as there is a risk of vascular embolization.
There are published reports of dermal filler use in the area of the eye resulting in ocular vessel occlusion (i.e.: blindness). Avoid the use of Revanesse Versa when there is an active inflammatory process (pimples, hives, rashes, cysts) until the process has resolved.
Injection site reactions (for example: redness, temporary swelling, tenderness or pain) have been observed, and are short term in duration (less than seven days).
Any reactions in excess of this anticipated reaction should be reported to your doctor.
All injections / transcutaneous procedures carry the risk of infection. Care must be taken to follow standard precautions for injections.
Dermal fillers have an inherent risk of keloid formation and hyperpigmentation at the injection site.
Patients historically prone to these conditions should avoid dermal fillers.
If immediate blanching occurs, the injection should be stopped and the area massaged until it returns to a normal color. Blanching may represent a vessel occlusion.
If normal skin coloring does not return, do not continue with the injection.
Treat in accordance with American Society for Dermatologic Surgery guidelines, which include hyaluronidase injection.
Warning: Introduction of product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction.
Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure.
Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
In order to minimize the risks of potential complications, this product should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
Health care practitioners are encouraged to discuss all potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications.
Revanesse Versa should not be mixed with any other products before implantation.
It is imperative that Revanesse Versa patients with adverse inflammatory reactions that persist for more than one week report this immediately to their doctor.
Please contact the company Prollenium Medical Technologies immediately at 1-866-353-3017.
Adverse Experiences
Patients were treated between 18 May 2015 and 04 April 2016. The database for the initial phase of the study reflected data collected through 03 March 2016 and included 163 patients. T
he database for the retreatment study reflected data collected through 07 September 2016 and included 71 patients. There were 4 investigational sites.
The study was a randomized, multicenter, double blind, split-face study in subjects seeking nasolabial fold (NLF) correction.
Subjects were treated with Revanesse® Versa™ in the NLF on one side of the face and Comparator in the NLF on the other side of the face.
The Comparator used was an FDA-approved crosslinked hyaluronic acid dermal filler which is legally marketed with similar indications for use.
The side of the face for each product was randomly assigned. Randomization followed a 1:1 within-subject Comparator model of augmentation correction of NLFs.
The investigator performing the evaluations and the subject were blinded to the treatment; injections of the study product were performed by an unblinded injecting investigator.
The primary efficacy variable was change from Baseline to Visit 6/Week 24 in Wrinkle Severity Rating Scale (WSRS) score (i.e., WSRS at Visit 1 – WSRS at Visit 6).
Summary statistics and 95% confidence interval (CI) were presented for the change scores for each treatment and for the difference in change scores between the two treatments (Comparator minus Test product, i.e., Comparator minus Revanesse® Versa™).
The 95% CI for difference between treatments was constructed assuming a normal distribution of the change scores.
If the upper bound of this 95% CI was less than the pre-specified non inferiority limit of 0.50, the Test product would be claimed to be non-inferior to the Comparator product.
Subjects meeting the inclusion and exclusion criteria were randomized to treatment with Revanesse® Versa™ in the NLF on one side of the face and Comparator in the NLF on the other side of the face. SYM2014-02 Retreatment - Subjects could have open-label retreatment as needed with Revanesse® Versa™ at 6 months if their WSRS scores had returned to baseline, or as needed to achieve optimal correction if their WSRS scores had not returned to baseline, and were followed for a total of 12 months. The study design was appropriate for the indication studied.
Validated methods of data collection, analysis, and evaluation were used. Of the 163 treated subjects, one or more injection-site TEAEs during the study were reported for 114 (69.9%) with Revanesse®Versa™ treatment and 137 (84.0%) with Comparator treatment, and most events were considered by the investigator to\ Table 2: SYM2014-02 Main Study – Most Frequently Occurring Injection Site Treatment-Emergent Adverse Events (TEAEs) by MedDRA Preferred Term for Intent-to-Treat Population Most frequently occurring injection site TEAEs are those that were reported by 5% or more subjects with either treatment.
Counts reflect numbers of subjects reporting one or more injection site TEAEs that map to the MedDRA (version
15.1) system organ class/preferred term.
At each level of summarization (system organ class or preferred term) subjects reporting more than one injection site TEAE are only counted once.
Directions For Assembly
-
Assembly Of Needle To Syringe
NOTE: The correct injection technique is crucial to treatment success and patient satisfaction. Revanesse® Versa™ + should only be injected by a practitioner qualified according to local laws and standards. The graduation on the syringe is not precise and should be used as a guide only. The amount of material to be injected is best determined by visual and tactile assessment by the user
Pre-Treatment Guidlines
Your doctor will examine you, and will explain the procedure and the potential risks. You will be asked about your health, your medical history, and the medications you take and have recently taken. You should advise your doctor of any of your concerns before the procedure, and discuss any questions related to the procedure.
Treatment Procedures
The doctor will prepare the area to be treated. There is some pain associated with the injection of the product. You should discuss your concerns about injection related pain with your doctor. The doctor will inject the filler, during which you may experience tenderness or a stinging sensation in the area of the injection. The procedure does not take long, often 15 to 30 minutes.
Injection Technique
-
Sterile Needles
-
PATIENT INSTRUCTION
Frequently Asked Questions
What is Revanesse® Versa™+?
Revanesse® Versa™+ is hyaluronic acid dermal filler. Hyaluronic acid is a naturally occurring substance that is found within the body. It may be produced by bacteria and purified for use as injectable soft tissue filler in order to correct the appearance of facial wrinkles and creases, (nasolabial folds). The product is approved for use in the U.S. by the Food and Drug Administration for the cosmetic treatment of facial wrinkles and creases.
How does Revanesse® Versa™+ work?
Revanesse® Versa™+ is an injection into the facial tissue to improve the appearance of facial wrinkles and creases, such as nasolabial folds. The injection results in a smoothing effect. The product is intended for individuals 22 years of age or more seeking correction of their facial wrinkles and creases.
Are there any warnings I should be aware of?
If you have an adverse inflammatory reaction, such as redness, pain and swelling that persist for one week or more after treatment with Revanesse® Versa™+, you should report this immediately to your doctor. If you are under the age of 22 you should not be treated with Revanesse® Versa™+. Warning: One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
Are there any reasons why I should not (contraindications) receive the Revanesse® Versa™ injection?
You should not be treated with Revanesse® Versa™+ if you:
- are pregnant or breastfeeding, as the safety of these products for use during pregnancy, or in women who are breastfeeding, has not been studied
- have a history of hypertrophic scarring or keloid formation
- have evidence of scars at the intended treatment sites
- have acne and / or other inflammatory diseases of the skin, such as rosacea, seborrheic dermatitis, and psoriasis,
- have allergic history including;
- severe allergic reactions (anaphylaxis),
- heightened immune responses to common allergens, especially inhaled allergens and food allergens (atopy),
- allergy to hyaluronic acid products,
- Streptococcal proteins or have plans to undergo administration of graded doses of allergens (desensitization therapy) during treatment with Revanesse® Versa™+. - have acute or chronic skin disease, such as seborrheic dermatitis or rosacea, in or near the injection sites, or any infection or unhealed wound of the face
- are under concomitant anticoagulant therapy, antiplatelet therapy, or have a history of bleeding disorders, clotting disorders such as hemophilia or connective tissue disorders such as systemic lupus erythematosus You should never use Revanesse® Versa™+ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment, as there is a possible risk of inflammation at the treatment site if these procedures are performed before treatment.
Safety
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Troubleshooting
If you have any questions about your treatment with Revanesse® Versa™+, or do not understand something about dermal filler injections, you should ask your doctor, or his or her staff, to explain. You should feel free to discuss your concerns openly with your doctor in order to better understand your options for treatment of facial wrinkles and creases (nasolabial folds)
Administration
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Post Marketing Surveillance
Postmarket surveillance for Revanesse® Versa and Revanesse® Versa+ reported the following adverse events (AEs) with 5 or greater instances: swelling, bruising, and lumps for the United States. In some instances, patients reporting these adverse events experienced symptoms that were severe, prompting additional medical evaluation. When required, treatment included massage, cold compresses, analgesics, antibiotics, antihistamines, topical steroids, oral corticosteroids, and enzymatic degradation (with hyaluronidase) of the product.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
Following treatment, a cold compress or ice may be applied for any bruising or swelling at the injection site. You may also gently massage the area with constant pressure for several minutes. The most common side effects include: bruising, redness, swelling, pain, and itching.
You should contact your doctor if you experience redness, itching or pain at the injection site for recommendations for over-the-counter treatment (such as Tylenol, Motrin or Benadryl). Most side effects occur shortly after injection and go away within two weeks. If you experience a reaction that lasts longer than two weeks, or what you think may be a delayed reaction to the product, contact your doctor.
You should seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site (blanching) or any other unexpected symptoms. While rare, unexpected symptoms include unusual pain, vision changes, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, visual changes, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure.
Additional side effects of dermal fillers less commonly reported include: infections, lumps and bumps, discoloration or change in pigmentation. It is rare for patients to have a delayed onset reaction or an infection such as cold sores (herpetic sores).
Rare, but serious risks, of dermal fillers include: scarring, blurred vision, partial vision loss, and blindness if the dermal filler is inadvertently injected into a blood vessel. In occasionally rare cases, there have been reports of unintentional injection of the product into a blood vessel with dermal filler products. It is recommended that doctors take care to avoid injection into blood vessels (especially around the forehead, nose and eye area) for these reasons, allergic reaction that may lead to a severe reaction (anaphylactic shock) that requires emergency medical help.
User Assistance Information
If you require immediate assistance, please contact your health care provider. For further assistance, please contact Prollenium Medical Technologies Inc. at 1-866-353-3017 (24 hours a day).
Patents 8,450,475; 8,357,795; 8,822,676; 9,089,519; 9,238,013; 9,358,322; 10,391,202; 10,485,896
Lips +
PACKAGE INSERT
PATIENT INSTRUCTION
PACKAGE INSERT
Description
Revanesse® Lips™ + is manufactured by Prollenium Medical Technologies, and is a biocompatible, biodegradable, non-pyrogenic, sterile, injectable viscoelastic clear colorless hydrogel based on bioresorbable BDDE cross-linked hyaluronan (HA) (22 – 28 mg / mL concentration) containing 0.3% lidocaine. The HA is produced by the Streptococcus species of bacteria. The gel is delivered in a pre-filled disposable glass syringe. Each syringe is fitted with a Luer lock adaptor, a plunger rod, a rubber stopper tip cap, and a finger grip. Each box of Revanesse® Lips™+ contains two 1.0 mL or 1.2 mL syringes of Revanesse® Lips™+ along with two 0.5-inch 30-gauge sterile needles. The syringe is labeled with the product name, the manufacturer, lot number, and expiration date. There is a removable portion of the label, which can be affixed to the patient record.
Indication
Revanesse® Lips™ + is indicated for submucosal implantation for lip augmentation in patients 22 years of age or older.
How Supplied
Revanesse® Lips™ + is supplied in a disposable glass syringe with a Luer-Lok® fitting. Revanesse® Lips™ + is packed with two 1.0 mL or 1.2 mL syringes and two sterilized needle(s) 30 G x ½” in a peel tray contained in a carton. A patient record label is a part of the syringe label. This label is to be at
Self Life and Storage
Revanesse® Lips™ + must be used prior to the expiration date printed on the package. Store at a temperature of up to 5 to 25° C (77° F). Do not freeze. Protect from sunlight. Do not use if the package is damaged.
Contraindications
- Patients who develop hypertrophic scarring or keloid formation should not be treated with Revanesse® Lips™+.
- Patients with evidence of scars at the intended treatment sites should not be treated with Revanesse® Lips™+.
- Never use Revanesse® Lips™+ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment.
- Patients with acne and / or other inflammatory diseases of the skin should not be treated with Revanesse® Lips™+.
- Patients with unattainable expectations should not be treated with Revanesse® Lips™+.
- Patients with multiple severe allergies, or with allergic history including anaphylaxis, multiple severe allergies, atopy, should not be treated with Revanesse® Lips™+.
- Patients with allergies to hyaluronic acid products, or Streptococcal proteins should not be treated with Revanesse® Lips™+
- Patients who have plans to undergo desensitization therapy should not be treated with Revanesse® Lips™+.
- Revanesse® Lips™ + should not be used in patients with acute or chronic skin disease in or near the injection sites, or with any infection or unhealed wound of the face.
- Patients who are under concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders, coagulation defects or connective tissue disorders should not use this product.
- Revanesse® Lips™+ contains lidocaine, and is contraindicated for patients with a history of allergies or sensitivities to such material and should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
- Revanesse® Lips™+ is only intended for submucosal injection into the lips and must not be injected into blood vessels. Implantation of Revanesse® Lips™+ into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena
Warnings
Do not inject Revanesse® Lips™+ into eye contours. Serious adverse events have been reported related to the use of dermal fillers in the area of the eye.
- Rare, but serious, adverse events associated with the intravascular injection of softtissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures.
- Defer use of Revanesse® Lips™ + at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
- Injection site reactions (e.g., lip swelling, lip pain, and contusion) are associated with Revanesse® Lips™ +, including short-term minor or moderate inflammatory symptoms starting shortly after treatment of lips
- Revanesse® Lips™ + must not be implanted into blood vessels. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar area. It is thought to result from the injury, obstruction, or compromise of blood vessels.
- Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
- As with all dermal filler procedures, Revanesse® Lips™ + should not be used in vascularrich areas. Use of similar products in these areas, such as glabella and nose, has resulted in cases of vascular embolization and symptoms consistent with ocular vessel occlusion, such as blindness.
- This product has not been evaluated in pregnant women, or women during lactation, and these individuals should not be treated with Revanesse® Lips™+.
- People 21 years of age and under should not be treated with Revanesse® Lips™+
Precautions
- Revanesse® Lips™ + is packaged for single use. Do not resterilize. Do not use if package is opened or damaged. Do not use product beyond the expiration date printed on the package.
- The safety or effectiveness of Revanesse® Lips™ + for the treatment of anatomic regions other than lips and nasolabial folds has not been established in controlled clinical studies.
- Limited safety and effectiveness information is available for Revanesse® Lips™+ for injection into the lips in men.
- As with all transcutaneous procedures, Revanesse® Lips™ + implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety of Revanesse® Lips™ + for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
- The safety in patients with known susceptibility to keloid formation has not been studied. Formation of keloids may occur after dermal filler injections. In a premarket study of Revanesse® Lips™ + the incidence and severity of adverse events in 53 subjects with Fitzpatrick Skin Types IV (n=27), V (n=9), and VI (n=17) was similar to that reported in the general population and no unique adverse events associated with these patient subgroups were observed.
- Hyperpigmentation may occur after dermal filler injections including Revanesse® Lips™+. Hyperpigmentation was not observed in the Revanesse® study of 158 subjects including subjects with Fitzpatrick Skin Types IV (n=27), V (n=9), and VI (n=17). Also, hyperpigmentation was not observed in any of the three previous Revanesse® product clinical studies involving 97 injections of Fitzpatrick skin types IV through V. There were no incidences of keloid formation in any of the studies.
- The safety profile for Revanesse® Lips™ + lip augmentation in persons of color is based upon information from 53 subjects with Fitzpatrick Skin Types IV, V and VI. Within this population, the incidence of adverse events was similar to the overall study population.
- Revanesse® Lips™ + should be used with caution in patients on immunosuppressive therapy.
- Bruising or bleeding may occur at Revanesse® Lips™ + injection sites. Patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the 3 weeks preceding treatment with Revanesse® Lips™ + have not been studied.
- After use, syringes and needles should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
- The safety of Revanesse® Lips™ + with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
- Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
- If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Revanesse® Lips™ +, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Revanesse® Lips™ + is administered before the skin has healed completely after such a procedure.
- Injection of Revanesse® Lips™ + into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- It is imperative that patients with adverse inflammatory reactions that persist for more than one week report this immediately to their physician.
Adverse Experiences
Potential adverse effects (e.g., complications) associated with the use of the device, as well as for other devices in the same category include: tenderness, swelling, firmness (induration), lumps/bumps (mass), bruising, pain, redness, discoloration, and itching. Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. For the specific adverse events that occurred in the clinical study, please see summary below.
Directions For Assembly
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Assembly Of Needle To Syringe
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Pre-Treatment Guidlines
Your doctor will examine you and will explain the procedure and the potential risks. You will be asked about your health, your medical history, and the medications you take and have recently taken. You should advise your doctor of any of your concerns before the procedure, and discuss any questions related to the procedure.
Treatment Procedures
The doctor will prepare the area to be treated. There is some pain associated with the injection of the product. You should discuss your concerns about injection related pain with your doctor. The doctor will inject the filler, during which you may experience tenderness or a stinging sensation in the area of the injection. The procedure does not take long, often 15 to 30 minutes.
Injection Technique
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Sterile Needles
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PATIENT INSTRUCTION
Frequently Asked Questions
What is Revanesse® Lips™ +?
Revanesse® Lips™ + is hyaluronic acid dermal filler. Hyaluronic acid is a naturally occurring substance that is found within the body. Hyaluronic acid is produced by bacteria and purified for use as injectable soft tissue filler in order to enhance the appearance of lips. Revanesse® Lips™+ is crosslinked with 1,4-butanediol diglycidyl ether (BDDE). BDDE is a chemical used to crosslink the hyaluronic acid in the dermal filler. Crosslinking is the process of chemically joining two or more molecules to form a network. The product also contains lidocaine. The product should not be used in patients with a history of allergies or sensitivities to such material and you should not be treated with the product if you have a previous hypersensitivity to local anesthetics of the amide type, such as lidocaine. The product is approved for submucosal implantation for lip augmentation in patients 22 years of age or older.
How does Revanesse® Lips™ + work?
Revanesse® Lips™+ is a gel that is injected directly into the lips using an ultrafine needle to temporarily plump the lips for lip enhancement in adults 22 years of age or older. The lidocaine in the gel improves the comfort of the injection by reducing sensitivity to pain.
Safety
If you are under the age of 22 you should not be treated with Revanesse® Lips™ +. Limited safety and effectiveness information is available for this product for injection into the lips in men. The same product has been evaluated in men for the treatment of facial wrinkles and creases, (nasolabial folds).
Troubleshooting
Call your doctor immediately if you have:
- Changes in your vision
- Signs of a stroke (including sudden difficulty speaking, numbness of weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
- White appearance of the skin
- Unusual pain during or shortly after treatment Be sure to call your doctor if you have:
- Significant pain away from the injection site
- Any Redness and/or visible swelling that lasts for more than a few days
- Any side effect that occurs weeks or months after treatment
- Any other Symptoms that cause you concern
Administration
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Post Marketing Surveillance
Revanesse® Lips™+ is identical in formulation to Revanesse® Versa™ +. Postmarket surveillance for Revanesse® Versa™ and Revanesse® Versa™+ reported the following adverse events (AEs) with 5 or greater instances: swelling, bruising, and lumps for the United States. In some instances, patients reporting these adverse events experienced symptoms that were severe, prompting additional medical evaluation. When required, treatment included massage, cold compresses, analgesics, antibiotics, antihistamines, topical steroids, oral corticosteroids, and enzymatic degradation (with hyaluronidase) of the product. Revanesse® Kiss™ + is the lips product marketed in the rest of the world markets, and is similar in composition, though not identical. There were no incidences of more than 5 of any adverse event type for Revanesse® Kiss™+ reported to the company, nor were there any contained in the literature.
Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.
Post-treatment Checklist
Following treatment, a cold compress or ice may be applied for any bruising or swelling at the injection site. You may also gently massage the area with constant pressure for several minutes.
The most common side effects include: bruising, redness, swelling, pain, and itching. You should contact your doctor if you experience redness, itching or pain at the injection site for recommendations for over-the-counter treatment (such as Tylenol, Motrin or Benadryl). Most side effects occur shortly after injection and go away within two weeks. If you experience a reaction that lasts longer than two weeks, or what you think may be a delayed reaction to the product, contact your doctor.
You should seek immediate medical attention if you develop symptoms such as unusual pain, vision changes, a white appearance of skin near the injection site (blanching) or any other unexpected symptoms. While rare, unexpected symptoms include unusual pain, vision changes, or any signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, visual changes, face drooping, severe headache, dizziness, or confusion) during or shortly after the procedure.
Additional side effects of dermal fillers less commonly reported include: infections, lumps and bumps, discoloration or change in pigmentation. It is rare for patients to have a delayed onset reaction or an infection such as cold sores (herpetic sores). Rare, but serious risks, of dermal fillers include: scarring, blurred vision, partial vision loss, and blindness if the dermal filler is inadvertently injected into a blood vessel. In occasionally rare cases, there have been reports of unintentional injection of the product into a blood vessel with dermal filler products. It is recommended that doctors take care to avoid injection into blood vessels (especially around the forehead, nose and eye area) for these reasons. In rare cases patients have experienced allergic reaction to dermal fillers that may lead to a severe reaction (anaphylactic shock) that requires emergency medical help.
User Assistance Information
If you require immediate assistance, please contact your health care provider. For further assistance, please contact Prollenium Medical Technologies Inc. at 1-866-353-3017 (24 hours a day).
Belotero Balance
PATIENT INSTRUCTION
PACKAGE INSERT
Description
BELOTERO BALANCE® is a sterile, bioresorbable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel device. BELOTERO BALANCE® is a bacterially fermented, injectable, hyaluronic-acid-based dermal filler. After extraction and purification, hyaluronic acid manufactured from streptococcal cultures is cross-linked with a binding agent 1,4-butanediol diglycidyl ether (BDDE) in two consecutively executed reactions and reconstituted in a physiologic buffer at pH 7 and concentration of 22.5 mg/mL.
Indication
BELOTERO BALANCE® is indicated for injection into the mid-to-deep dermis for correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.
How Supplied
HOW SUPPLIED BELOTERO BALANCE® is supplied in a blister pack containing 1-mL of sterile gel prefilled in a glass syringe and packaged with two sterile needles and two patient record labels. The individual treatment syringe is ready for injection. For single patient use only. Do not re-sterilize the needle. Do not use if package is opened or damaged. In the event that the package is opened or damaged, do not use the syringe and notify Merz North America,Incimmediatelyat 1-844-469-6379 or e-mail [email protected].
Self Life and Storage
BELOTERO BALANCE® should be stored at room temperature (up to 30°C/86°F), away from heat. DO NOT FREEZE. The product expiry date is located on the syringe and blister labels.
BELOTEROBALANCE® has a clear colorless (transparent) appearance. In the event that the syringe contains material that is not clear, do not use the syringe and notify Merz North America,Immediately at 1-844-469-6379 or email [email protected]. To place an order, contact Merz North America, Inc. at 1-844-469-6379.
Contraindications
- BELOTERO BALANCE® is contraindicated in patients with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies.
- BELOTEROBALANCE® containstraceamountsofgram-positivebacterialproteins, and iscontraindicated for patients with a history of allergies to such material.
- BELOTERO BALANCE® must not be implanted into blood vessels. Implantation of BELOTERO BALANCE® into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena.
Warnings
- Use of BELOTEROBALANCE® at specificsitesinwhichanactiveinflammatoryprocess (skin eruptions such as coldsores, cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled. Health care professionals should review and consider the patient’s medical history prior to injection.
- Introduction of BELOTERO BALANCE® into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to the underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Injection site responsestoBELOTEROBALANCE® have been observed, consistingmainly of short-term inflammatorysymptoms starting early after treatment and with 7 days duration or less. Refer to the ADVERSE EVENTS section for details.
Precautions
- In order to minimize the risks of potential complications, BELOTERO BALANCE® should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all the potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of the signs and symptoms of potential complications.
- BELOTERO BALANCE® is packaged and designed for single use only. Do not resterilize. Discard any unused product. Discard any partially used syringes.
- Do not use if the package is opened or damaged or beyond the expiration date cited on the package.
- The safety or effectiveness of BELOTERO BALANCE® for the treatment of dermal contour defects other than nasolabial folds has not been established in controlled clinical studies. The safety and effectiveness of BELOTERO BALANCE® use in the lips has also not been evaluated.
- As with all transcutaneous procedures, BELOTERO BALANCE injection carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The long term safety and effectiveness of BELOTERO BALANCE® beyond 96 weeks has not been investigated.
- Basedonclinicalstudies,patientsshouldbelimitedto6.0mlofBELOTEROBALANCE® peryear. Thesafetyofinjectinggreater amountshas not been established.
- As with all transcutaneous procedures, BELOTERO BALANCE® injection carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- ThesafetyofBELOTERO BALANCE® for useduringpregnancy,inbreastfeedingfemales, orinpatientsunder 21yearshasnot been established.
- The safety of BELOTERO BALANCE® in patients with known susceptibility to recurrent sorethroat, or OslerRendu endocarditishas not been studied.
- Injection of BELOTERO BALANCE® into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
- BELOTEROBALANCE® shouldbeusedwithcautioninpatientsonimmunosuppressivetherapy.
- Patients who are using substances that reduce coagulation, such as aspirin, non-steroidal anti-inflammatory drugs, and warfarin may, as with any injection, experience increased bruising or bleeding at injection sites.
- As with all invasive procedures, BELOTERO BALANCE® sessions should be conducted with aseptic technique including cleansing the patient’s face prior to injection and wearing sterile gloves when injecting. Observe universal precautions to minimize risks of potential contact with patient body fluids such as blood at the injection site.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- BELOTERO BALANCE® is a clear colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Merz North America, Inc. at 1-844-469-6379.
- Laser treatment, chemical peeling, or any other procedure based on active dermal response performed after treatment with BELOTERO BALANCE®mayincreasetheriskofaninflammatoryreactionattheinjectionsite.Similarly,theadministrationof BELOTEROBALANCE® before the skin has healed completely after such a procedure may also increase the risk of inflammatory reactions.
- BELOTERO BALANCE® is supplied in a syringe ready for use. BELOTERO BALANCE® should not be directly mixed with any other products prior to injection of thedevice. No studies of interactions of BELOTERO BALANCE® with drugs or other substances or implants have been made.
- The patient should be informed that he or she should minimize exposure of the treated area to excessive sun or heat, UV lamp exposure, Turkish baths, and extreme cold weather until any initial swelling and redness have resolved and puncture sites have healed.
Adverse Experiences
The safety of BELOTERO BALANCE® has been evaluated in three studies and 211 patients. These studies are described below.
Pivotal Clinical Study ControlledPhase (0-24 Weeks): In a randomized, controlled clinical trial,118 subjects at 6 centers,were injected with BELOTERO BALANCE® inone NLF and bovine collagen controldermal filler (Control) in the contralateral NLF to evaluate the safety and effectiveness of BELOTERO BALANCE® incomparison with the Control.Pre-printed diary forms were used by subjects to record specific signs and symptoms experienced during each of the first 14 days after initial and touch-up treatments. Subjects were instructed to rate each common treatment response listed on the diary as “Mild”, “Moderate”, “Severe”, or “None.” The combined rates of injection site responses reported by >5% of subjects in the pivotal clinical study and the Fitzpatrick Skin Type IV, V, and VI study are summarized by maximum intensity in Table 1 and by duration in Table 2. Adverse events recorded by investigators at study visits are presented in Table 3.
Open Label Extension (OLEX)Phase (24-96 Weeks): 95 of 118 subjects who completed the 24 week controlled-phase of the pivotal study received additional treatments with BELOTERO BALANCE® from Weeks 24 to 96 afterthe initial treatment. Follow-up visits occurred at 24, 32, 48, 72, and 96 weeks afterthe initial treatment. At the Week 24 study visit all enrolleds ubjects received BELOTERO BALANCE® in both NLF to achieve optimal correction. At the Week 32 visit, subjects were allowed a touch-up treatment on one side to balance any observed differences. Subjects could receive additional treatmentsto both NLFs at weeks 48, 72, or 96 if their wrinkle severity score met the injection criteria (SRS of 2 or 3). No singleAE was reported with more than a 5% rate of incidence during the OLEX phase and the safety profile observed during the OLEX phase was similarto that described above during the controlled-phase. Fitz patrick Skin Type IV, V and VI Study:
The safety and effectiveness o fBELOTERO BALANCE® was evaluated in 93 subjects with Fitz patrick skin photo type scores of IV, V, and Vat3 U.S.Centers during a 24 week open label study. Subjects received an initial treatment of BELOTERO BALANCE® and were eligible to receive an additional touch-up treatment2 weeks after the initial treatment if necessary. Subjectfollow-upvisitsoccurredatweeks2,4,8, 12, 16,and24weeks. Thesafetyprofile observed during this study was similarto that observed in the pivotal controlled clinical study.
Directions For Assembly
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Assembly Of Needle To Syringe
To assure proper needle attachment, use needles provided.
a. To attach needle to syringe, open the needle packaging to expose the needle hub. For use of needles other than the needle(s) provided with this package, follow the directions provided with the needle(s).
b. Remove the Luer syringe cap from the distal end of the syringe prior to attaching the needle.
c. Holding the luer lock fitting of the syringe, twist the needle onto the syringe. The needle must be tightened securely to the syringe and primed with BELOTERO BALANCE® . Do not over-tighten as this may break the needle and/or dislodge the syringe.
d. Pull off the needle guard to expose needle e. If excess implant is on the surface of the Luer lock fittings, it will need to be wiped clean with sterile gauze. Slowly push the syringe plunger until the implant material extrudes from the end of the needle. If leakage is noted at the Luer fitting, it may be necessary to remove the needle and clean the surfaces of the Luer fitting or, in extreme cases, replace both the syringe and the needle.
Pre-Treatment Guidlines
- Your doctor will answer all your questions and prepare you for the treatment. You can use the space at the end of this Guide to write down your questions before you see your doctor.
- Your doctor will ask you questions about your medical history.
- Your doctor will clean the area where the injections will be given.
- You and your doctor will determine if a topical or local anesthetic is needed.
Pre-Treatment Guidlines
- Your doctor will inject small amounts of BELOTERO BALANCE® into the skin using a thin needle until you have received the desired correction.
- Your doctor may gently massage the treatment area to ensure the product is evenly distributed.
Injection Technique
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Sterile Needles
- Follow national, local, or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not reshield used needles. Recapping by hand is a hazardous practice and should be avoided.
- Discard unshielded needles in approved sharps collectors.
PATIENT INSTRUCTION
Frequently Asked Questions
WHAT IS BELOTERO BALANCE®?
BELOTERO BALANCE® is a clear, hyaluronic acid gel and the chemical BDDE to make it last longer. Hyaluronic acid is a naturally occurring substance in the body. One of the natural functions of hyaluronic acid in the skin is to help retain natural moisture and softness.
WHAT IS BELOTERO BALANCE® USED FOR?
BELOTERO BALANCE® is used to smooth out and fill in moderate to severe folds or wrinkles, such as the creases that extend from the corner of the nose to the corner of the mouth (nasolabial folds) as shown in figure 1 below.
Safety
You should not use BELOTERO BALANCE®
- if you have severe allergies or a history of allergic reactions to hyaluronic acid, local anesthetics such as lidocaine, or to small amounts of protein from bacteria. Injections in such patients could result in allergic reactions, anaphylactic shock, or death. If you are unsure about this, talk about the details of your medical history with your doctor and the risks versus the benefits of using BELOTERO BALANCE®.
- Warning: One of the risks with using BELOTERO BALANCE® is unintentional injection into a blood vessel. The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weaknesses in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
- If you easily develop big scars or keloids on your skin do not use BELOTERO BALANCE® because you will most likely get a scar where BELOTERO BALANCE® is injected..
Troubleshooting
Ask your doctor if you will benefit from treatment with BELOTERO BALANCE® (+). If you and your doctor decide that BELOTERO BALANCE® is for you, you will then talk about your complete medical history with your doctor. It is important to tell your doctor everything in your medical history, about all medicines and supplements that you are taking, any past and present allergies and their seriousness, and all current or past medical conditions you have had. Your doctor will discuss what your chances are for getting any of the side effects from injection of BELOTERO BALANCE® (+) and how serious they may be.
Administration
-
Post Marketing Surveillance
The following adverse events have been identified during post-approval use of BELOTEROBALANCE®. Because they are reported voluntarilyfrom a population of uncertainsize, it is not always possible to reliabl yes intimate their frequency or establish a causal connection to BELOTEROBALANCE®. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to BELOTEROBALANCE®: Allergic reactions including Quincke’s edema,anaphylaxis,rash,hives,necrosis, inflammation, granuloma, indurations, nodules, hematoma, Tyndall effect, bumps, pustule, scarring, swelling, erythema, pain, edema, bruising, lumps, discoloration, infection, migration/displacement, asymmetry, numbness, vascular occlusion, visual disturbance. Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. The following interventions have been reported: antibiotics, anti-inflammatories, corticosteroids, anti-histamines, analgesics, hyaluronidase, massage, warm compress, excision, drainage, and surgery. This information does not constitute and is not intended to be medical advice, a recommendation on how to treat an adverse event or an exhaustive list of possible interventions. Physicians should evaluate each case on an individual basis, and independently determine, based on their professional experience, what treatment(s) are appropriate, if any, fortheir patients.
Post-treatment Checklist
- Your health care provider will give you specific after treatment care instructions and what products to use or avoid after treatment.
- If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
- Within the first 12-24 hours, patients should avoid touching/pressing treated parts of the face, applying make-up to treated parts of the face, strenuous exercise, and consuming alcoholic beverages. Patients should also avoid taking anti-coagulation, anti-platelet, or thrombolytic medications, aspirin or non-steroidal anti-inflammatory drugs or other substances known to increase coagulation time for three days after treatment.
- Your doctor may periodically apply an ice pack to the treatment area to help reduce swelling.
User Assistance Information
For further information please call Merz North America at (844) 469-6379.
Belotero Balance Plus
PATIENT INSTRUCTION
PACKAGE INSERT
Description
BELOTERO BALANCE® (+) is a sterile, bioresorbable, non-pyrogenic, viscoelastic, clear, colorless, homogeneous gel. BELOTERO BALANCE® (+) is a bacterially fermented, injectable, hyaluronic-acid-based dermal filler. After extraction and purification, hyaluronic acid manufactured from streptococcal cultures is cross-linked with a binding agent 1,4-butanediol diglycidyl ether (BDDE) in two consecutively executed reactions and reconstituted in a physiologic buffer at pH 7 and concentration of 22.5 mg/mL. BELOTERO BALANCE® (+) contains 0.3% lidocaine hydrochloride to reduce pain on injection.
Indication
BELOTERO BALANCE® (+) is indicated for injection into the mid-to-deep dermis for correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.
How Supplied
BELOTERO BALANCE® (+) is supplied in a blister pack containing 1-mL of sterile gel prefilled in a glass syringe and packaged with two sterile needles and two patient record labels. The individual treatment syringe is ready for injection. For single patient use only. Do not re-sterilize the needle or syringe. Do not use if package is opened or damaged. In the event that the package is opened or damaged, do not use the syringe and notify Merz North America, Inc. immediately at 1-844-469-6379 or e-mail [email protected]
Self Life and Storage
BELOTERO BALANCE® should be stored at room temperature (up to 30°C/86°F), away from heat. DO NOT FREEZE. The product expiry date is located on the syringe and blister labels.
BELOTEROBALANCE® has a clear colorless (transparent) appearance. In the event that the syringe contains material that is not clear, do not use the syringe and notify Merz North America,Immediately at 1-844-469-6379 or email [email protected]. To place an order, contact Merz North America, Inc. at 1-844-469-6379.
Contraindications
- BELOTERO BALANCE® (+) is contraindicated in patients with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies.
- BELOTERO BALANCE® (+) is not intended to be used in patients with known hypersensitivity to lidocaine or anesthetics of the amide type.
- BELOTERO BALANCE® (+) contains trace amounts of gram-positive bacterial proteins, and is contraindicated for patients with a history of allergies to such material.
- BELOTERO BALANCE® (+) must not be implanted into blood vessels. Implantation of BELOTERO BALANCE® (+) into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena.
Warnings
- Use of BELOTERO BALANCE® (+) at specific sites in which an active inflammatory process (skin eruptions such as cold sores, cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled. Health care professionals should review and consider the patient’s medical history prior to injection.
- Introduction of BELOTERO BALANCE® (+) into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example, inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to the underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and possibly evaluation by an appropriate health care practitioner specialist should an intravascular injection occur.
- Common treatment responses to BELOTERO BALANCE® (+) have been observed, consisting mainly of short-term inflammatory symptoms starting early after treatment and with 17 days duration or less. Refer to the ADVERSE EVENTS section for details.
Precautions
- In order to minimize the risks of potential complications, BELOTERO BALANCE® (+) should only be used by health care practitioners who have appropriate training, experience, and who are knowledgeable about the anatomy at and around the site of injection.
- Health care practitioners are encouraged to discuss all the potential risks of soft tissue injection with their patients prior to treatment and ensure that patients are aware of the signs and symptoms of potential complications.
- BELOTERO BALANCE® (+) is packaged and designed for single use only. Do not re-sterilize. Discard any unused product. Discard any partially used syringes.
- Do not use if the package is opened or damaged or beyond the expiration date cited on the package.
- The safety or effectiveness of BELOTERO BALANCE® (+) for the treatment of dermal contour defects other than nasolabial folds has not been established in controlled clinical studies. The safety and effectiveness of BELOTERO BALANCE® (+) use in the lips has also not been evaluated. • As with all transcutaneous procedures, BELOTERO BALANCE® (+) injection carries a risk of infection. Standard precautions associated with injectable materials should be followed.
- The safety of BELOTERO BALANCE® (+) for use during pregnancy, in breastfeeding females, or in patients under 21 years has not been established.
- The safety of BELOTERO BALANCE® (+) in patients with known susceptibility to recurrent sore throat, or Osler Rendu endocarditis has not been studied.
- Injection of BELOTERO BALANCE® (+) into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes. Page 3 of 25
- BELOTERO BALANCE® (+) should be used with caution in patients on immunosuppressive therapy. • Patients who are using substances that reduce coagulation, such as aspirin, non-steroidal antiinflammatory drugs, and warfarin may, as with any injection, experience increased bruising or bleeding at injection sites.
- As with all invasive procedures, BELOTERO BALANCE® (+) sessions should be conducted with aseptic technique including cleansing the patient’s face prior to injection and wearing sterile gloves when injecting. Observe universal precautions to minimize risks of potential contact with patient body fluids such as blood at the injection site.
- After use, treatment syringes and needles may be potential biohazards. Handle and dispose of these items in accordance with accepted medical practice and applicable local, state, and federal requirements.
- BELOTERO BALANCE® (+) is a clear colorless gel without particulates. In the event that the content of a syringe shows signs of separation and/or appears cloudy, do not use the syringe and notify Merz North America, Inc. at 1-844-469-6379 .
- Laser treatment, chemical peeling, or any other procedure based on active dermal response performed after treatment with BELOTERO BALANCE® (+) may increase the risk of an inflammatory reaction at the injection site. Similarly, the administration of BELOTERO BALANCE® (+) before the skin has healed completely after such a procedure may also increase the risk of inflammatory reactions.
- BELOTERO BALANCE® (+) is supplied in a syringe ready for use. BELOTERO BALANCE® (+) should not be directly mixed with any other products prior to injection of the device. No studies of interactions of BELOTERO BALANCE® (+) with drugs or other substances or implants have been made.
- The patient should be informed that he or she should minimize exposure of the treated area to excessive sun or heat, UV lamp exposure, Turkish baths, and extreme cold weather until any initial swelling and redness have resolved and puncture sites have healed.
- Care should be taken to determine the risk versus the benefit for patients with congenital methemoglobinemia, with glucose-6-phosphate dehydrogenase deficiencies, and with patients who are receiving concomitant treatment with methemoglobin-inducing agent.
- The long term safety and effectiveness of BELOTERO BALANCE® beyond 96 weeks has not been investigated.
- Based on clinical studies, patients should be limited to 6.0 ml of BELOTERO BALANCE® per year. The safety of injecting greater amounts has not been established.
Adverse Experiences
BELOTERO BALANCE® The safety of BELOTERO BALANCE® has been evaluated in three studies and 211 patients. These studies are described below.
- Pivotal Clinical Study Controlled Phase (0 – 24 Weeks): In a randomized, controlled clinical trial, 118 subjects at 6 centers were injected with BELOTERO BALANCE® in one NLF and bovine collagen dermal filler (Control) in the contralateral NLF to evaluate the safety and effectiveness of BELOTERO BALANCE® in comparison with the Control. Pre-printed diary forms were used by subjects to record specific signs and symptoms experienced during each of the first 14 days after initial and touch-up treatments. Subjects were instructed to rate each common treatment response listed on the diary as “Mild”, “Moderate”, “Severe”, or “None.” The combined rates of injection site responses reported by >5% of subjects in the pivotal clinical study and the Fitzpatrick Skin Type IV, V, and VI study are summarized by maximum intensity in Table 1 and by duration in Table 2. Adverse events recorded by investigators at study visits are presented in Table 3.
- Open Label Extension (OLEX) Phase (24 – 96 Weeks): 95 of 118 subjects who completed the 24 week controlled-phase of the pivotal study received additional treatments with BELOTERO BALANCE® from Weeks 24 to 96 after the initial treatment. Follow-up visits occurred at 24, 32, 48, 72, and 96 weeks after the initial treatment. At the Week 24 study visit all enrolled subjects received BELOTERO BALANCE® in both NLFs to achieve optimal correction. At the Week 32 visit, subjects were allowed a touch-up treatment on one side to balance any observed differences. Subjects could receive additional treatments to both NLFs at weeks 48, 72, or 96 if their wrinkle severity score met the injection criteria (SRS of 2 or 3). No single AE was reported with more than a 5% rate of incidence during the OLEX phase and the safety profile observed during the OLEX phase was similar to that described above during the controlled-phase.
- Fitzpatrick Skin Type IV, V and VI Study: The safety and effectiveness of BELOTERO BALANCE® was evaluated in 93 subjects with Fitzpatrick skin phototype scores of IV, V, and VI at 3 U.S. centers during a 24 week open label study. Subjects received an initial treatment of BELOTERO BALANCE® and were eligible to receive an additional touch-up treatment 2 weeks after the initial treatment if necessary. Subject follow-up visits occurred at weeks 2, 4, 8, 12, 16, and 24 weeks. The safety profile observed during this study was similar to that observed in the pivotal controlled clinical study.
Directions For Assembly
-
Assembly Of Needle To Syringe
To assure proper needle attachment, use needles provided.
a. To attach needle to syringe, open the needle packaging to expose the needle hub. For use of needles other than the needle(s) provided with this package, follow the directions provided with the needle(s).
b. Remove the Luer syringe cap from the distal end of the syringe prior to attaching the needle.
c. Holding the luer lock fitting of the syringe, twist the needle onto the syringe. The needle must be tightened securely to the syringe and primed with BELOTERO BALANCE® . Do not over-tighten as this may break the needle and/or dislodge the syringe.
d. Pull off the needle guard to expose needle e. If excess implant is on the surface of the Luer lock fittings, it will need to be wiped clean with sterile gauze. Slowly push the syringe plunger until the implant material extrudes from the end of the needle. If leakage is noted at the Luer fitting, it may be necessary to remove the needle and clean the surfaces of the Luer fitting or, in extreme cases, replace both the syringe and the needle.
Pre-Treatment Guidlines
- Your doctor will inject small amounts of BELOTERO BALANCE® (+) into the skin using a thin needle until you have received the amount of visible change.
- Your doctor may gently massage the treatment area to ensure the product is evenly distributed.
Treatment Procedures
- Your doctor will inject small amounts of BELOTERO BALANCE® (+) into the skin using a thin needle until you have received the amount of visible change.
- Your doctor may gently massage the treatment area to ensure the product is evenly distributed.
Injection Technique
-
Sterile Needles
- Follow national, local, or institutional guidelines for use and disposal of medical sharp devices. Obtain prompt medical attention if injury occurs.
- To help avoid needle breakage, do not attempt to straighten a bent needle. Discard it and complete the procedure with a replacement needle.
- Do not re-shield used needles. Recapping by hand is a hazardous practice and should be avoided.
- Discard unshielded needles in approved sharps collectors.
PATIENT INSTRUCTION
Frequently Asked Questions
What is BELOTERO BALANCE® (+)?
BELOTERO BALANCE® (+) is a clear, hyaluronic acid gel and a small quantity of an anaesthetic (lidocaine), to reduce the sensation of pain and the chemical BDDE to make it last longer. Hyaluronic acid is a naturally occurring substance in the body. One of the natural functions of hyaluronic acid in the skin is to provide firmness and hold water in the deep portions of the skin (dermis). Lidocaine helps to improve the comfort of the injection.
What is BELOTERO BALANCE® (+) use for? BELOTERO BALANCE® (+) is used to smooth out and fill in moderate to severe folds or wrinkles, such as the creases that extend from the corner of the nose to the corner of the mouth (nasolabial folds) as shown in Figure 1 below. Figure 1. Facial Nasolabial Fold
Why add Lidocaine to BELOTERO BALANCE®? An anesthetic medicine (lidocaine) was added to BELOTERO BALANCE® to reduce pain and discomfort during and after injection.
Safety
You should not use BELOTERO BALANCE® (+)
- if you have severe allergies or a history of allergic reactions to hyaluronic acid, local anesthetics such as lidocaine, or to small amounts of protein from bacteria. Injections in such patients could result in allergic reactions, anaphylactic shock, or death.
- If you are unsure about this, talk about the details of your medical history with your doctor and the risks versus the benefits of using BELOTERO BALANCE® (+).
Warning: One of the risks with using BELOTERO BALANCE® (+) is unintentional injection into a blood vessel.
The chances of this happening are very small, but if it does happen, the complications can be serious, and may be permanent.
These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin.
If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weaknesses in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
Do not use BELOTERO BALANCE® (+) if you have an allergic reaction to lidocaine or similar anesthetics.
If you easily develop big scars or keloids on your skin do not use BELOTERO BALANCE® (+) because you will most likely get a scar where BELOTERO BALANCE® (+) is injected.
Troubleshooting
Ask your doctor if you will benefit from treatment with BELOTERO BALANCE® (+). If you and your doctor decide that BELOTERO BALANCE® (+) is for you, you will then talk about your complete medical history with your doctor. It is important to tell your doctor everything in your medical history, about all medicines and supplements that you are taking, any past and present allergies and their seriousness, and all current or past medical conditions you have had. Your doctor will discuss what your chances are for getting any of the side effects from injection of BELOTERO BALANCE® (+) and how serious they may be.
Administration
-
Post Marketing Surveillance
The following adverse events have been identified during post-approval use of BELOTEROBALANCE®. Because they are reported voluntarilyfrom a population of uncertainsize, it is not always possible to reliabl yes intimate their frequency or establish a causal connection to BELOTEROBALANCE®. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to BELOTEROBALANCE®: Allergic reactions including Quincke’s edema,anaphylaxis,rash,hives,necrosis, inflammation, granuloma, indurations, nodules, hematoma, Tyndall effect, bumps, pustule, scarring, swelling, erythema, pain, edema, bruising, lumps, discoloration, infection, migration/displacement, asymmetry, numbness, vascular occlusion, visual disturbance. Delayed-onset inflammation near the site of dermal filler injections is one of the known adverse events associated with dermal fillers. Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own. The following interventions have been reported: antibiotics, anti-inflammatories, corticosteroids, anti-histamines, analgesics, hyaluronidase, massage, warm compress, excision, drainage, and surgery. This information does not constitute and is not intended to be medical advice, a recommendation on how to treat an adverse event or an exhaustive list of possible interventions. Physicians should evaluate each case on an individual basis, and independently determine, based on their professional experience, what treatment(s) are appropriate, if any, fortheir patients.
Post-treatment Checklist
- Your health care provider will give you specific after treatment care instructions.
- If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.
- Within the first 12-24 hours, patients should avoid touching/pressing treated parts of the face, applying make-up to treated parts of the face, strenuous exercise, and consuming alcoholic beverages. Patients should also avoid taking anti-coagulation, anti-platelet, or thrombolytic medications, aspirin or non-steroidal anti-inflammatory drugs or other substances known to increase coagulation time for three days after treatment.
- Your doctor may periodically apply an ice pack to the treatment area to help reduce swelling.
User Assistance Information
For further information please call Merz North America at (844) 469-6379.