Clinical Study of Restylane® / Perlane®

The results of the blinded evaluator assessment of NLF wrinkle severity for Restylane and control (Perlane) are presented in Table 15. In the primary effectiveness assessment at 12 weeks, 77% of the Restylane and 87% of the control patients had maintained at least a 1-point improvement over baseline.

Table 15: Blinded Evaluator Wrinkle Severity Response Scores

TIME POINT NO. OF RESTYLANE PATIENTS NO. OF RESTYLANE PTS. MAINTAINING ≥ 1 UNIT IMPROVEMENT OF NLF ON WSRS NO. OF PERLANE PATIENTS NO. OF PERLANE PTS. MAINTAINING ≥ 1 UNIT IMPROVEMENT OF NLF ON WSRS
6 weeks 136 113 (83%)1 136 121 (89%)1
12 weeks 140 108 (77%)1 141 122 (87%)1
24 weeks 140 103 (74%)1 138 87 (63%)1

All p-values < 0.0001 based on t-test compared to baseline condition.

At 12 weeks, 7/19 (37%) subjects were rated as improved on their GAIS assessment by the Blinded Evaluator. At 12 weeks, all (100%) subjects rated themselves as improved on their GAIS assessment.

PARAMETER N N SUBJECTS WITH LIP IMPROVEMENT PERCENT 90% CL P-VALUE1
Lip Improvement Using the Blinded Evaluator’s Assessment1 20 19 7 37% (0.19, 0.58) 0.820
Lip Improvement Using the Treating Investigator’s Assessment 20 19 19 100% (0.85, 1.00) < 0.001
Lip Improvement Using the Subject’s Assessment 20 17 17 100% (0.84, 1.00) < 0.001

Due to the protocol deviation, the live blinded evaluator’s assessment was a photo assessment.

Directions for Assembly

Use the thumb and forefinger to hold firmly around both the glass syringe barrel and the Luer-Lok adapter. Grasp the needle shield with the other hand. To facilitate proper assembly, both push and rotate firmly.

Pre-treatment Guidelines

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 Procedure

  1. It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the treatment.
  2. Advise the patient of the necessary precautions before commencing the procedure.
  3. A consent form should be utilized.
  4. Assess the patient’s need for appropriate anesthetic treatment for managing comfort, i.e., topical anesthetic, local or nerve block.
  5. 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.
  6. Sterile gloves are recommended while injecting.
  7. Before injecting, press rod carefully until a small droplet is visible at the tip of the needle.
  8. Restylane 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 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.
  9. Perlane is administered using a thin gauge needle (27 G TW x ½” or 29 G TW x ½”). The needle is inserted at an approximate angle of 30° parallel to the length of the wrinkle or fold. Perlane should be injected into the deep dermis to superficial layer of the subcutis.
  10. Inject Restylane applying even pressure on the plunger rod. 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 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.
  13. 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.
  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 an overcorrection has occurred, massage the area firmly between your fingers or against an underlying area to obtain optimal results.
  15. 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.
  16. If the wrinkles 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.
  17. 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.
  18. 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.

HOW SUPPLIED

  1. Restylane is supplied in a disposable glass syringe with a Luer-Lok fitting. Restylane-L is co-packed with sterilized needle(s) as indicated on the carton (29 G x ½”).
  2. Perlane is supplied in a disposable glass syringe with a Luer-Lok fitting. Perlane-L 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.”
  3. 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.
  4. The contents of the syringe are sterile.
  5. The volume in each syringe and needle gauge is as stated on the syringe label and on the carton.

Adverse Experiences

In 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.

Serious adverse events have been rarely reported. The only serious adverse events occurring in a frequency of 5 times or greater were abnormal sensitivity (hypersensitivity), injury to blood supply (vascular accidents), local tissue damage (necrosis) and infection/abscess. Hypersensitivity reactions have occurred immediately following implantation and up to 3 weeks and some required hospitalization.

Reported symptoms included swelling (including severe swelling of lips and face); redness; itching on chest and back; puffy, burning, watery, and itchy eyes; shortness of breath; headache; nausea and vomiting. Treatments used included steroids, diphenhydramine, unspecified intravenous medication, oxygen and various creams. Most hypersensitivity events have resolved within 1 to 14 days with or without treatment. Bruising and skin turning white as a result of injury to blood supply (blanching) have occurred immediately following injection with some cases resulting in necrosis. As a result of the necrosis some patients experienced scarring and dark spots on the skin.

Moderate to severe infection/abscess formations have occurred with an onset ranging from 3 days to one week post injection with approximately one month to resolution. Symptoms included swelling, redness, pain and hard nodules. Some patients required hospitalization for incision and drainage and intravenous (IV) antibiotic therapy. Culture results for the reports of infection or abscess varied. Treatment included various antibiotics and steroids in some cases.

Adverse events that have occurred at the injection sites include: discoloration, bruising, swelling, lumps/bumps, redness, pain, scarring, numbness/tingling, necrosis, and low blood supply due to blockage of a blood vessel (ischemia). Additional events include: bacterial infections, fainting (vasovagal reactions), herpetic eruptions, dilated small blood vessels (broken capillaries), and inflammatory reactions (swelling, redness, tenderness, hardness and acneform papules).

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 (e.g., swelling, redness, tenderness, or pain) 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. Localized superficial necrosis and scarring may occur after injection in or near dermal 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.

Injections of greater than 1.5 mL per lip (upper or lower) per treatment session significantly increases the occurrence of the total of moderate and 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 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

Learn more about Precautions & Contraindications of Restylane® / Perlane®.