|(injectable poly-L-lactic acid)||Rx only|
CONTRAINDICATIONS | WARNINGS
PRECAUTIONS | ADVERSE EVENTS
CLINICAL STUDIES | INDIVIDUALIZATION OF TREATMENT
HOW SUPPLIED | STORAGE | STERILITY | INSTRUCTIONS FOR USE
The Sculptra implant package (i.e., lyophilized vials and syringe) are provided sterile.
Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed physician or properly licensed practitioner.
Information for the use of SCULPTRA® is provided in this Labeling for Physicians and the Instructions for Use, as well as in Labeling for Patients. BEFORE USING SCULPTRA® PLEASE READ THE FOLLOWING INFORMATION THOROUGHLY. Please direct any questions to sanofi-aventis U.S. LLC Bridgewater, NJ 08807; 1-800-633-1610.
SCULPTRA® is an injectable implant containing microparticles of poly-L-lactic acid (PLLA), a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family, carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) and sterile water for injection (USP). SCULPTRA is available in 367.5 mg dose vials and is to be reconstituted prior to use by the addition of 5 mL of Sterile Water for Injection, USP (SWFI) to form a sterile non-pyrogenic suspension.
- SCULPTRA should not be used in any person who has hypersensitivity to any of the components of SCULPTRA (see DEVICE DESCRIPTION).
- SCULPTRA should not be used in patients with known history of or susceptibility to keloid formation or hypertrophic scarring.
- SCULPTRA has unique injection requirements, which include injection with tunneling technique or the depot technique (see the INSTRUCTIONS FOR USE). The safety of other methods of injection has not been evaluated in clinical studies.
- Do not overcorrect (overfill) the contour deficiency because the depression is expected to gradually improve during several weeks after injection as the treatment effect of SCULPTRA occurs (see INSTRUCTION FOR USE - Patient Treatment).
- SCULPTRA must not be implanted into blood vessels. Implantation of SCULPTRA into dermal vessels may cause vascular occlusion, infarction or embolic phenomena.
- Use of SCULPTRA in any person with active skin inflammation (skin eruptions such as cysts, pimples, rashes or hives) or infection in or near the treatment area should be deferred until the inflammatory or infectious process has resolved and is controlled.
- Injection site reactions to SCULPTRA have included delayed occurrence of subcutaneous papules and nodules, hematoma, bruising-ecchymosis, bleeding, edema, discomfort, inflammation, and erythema. The subcutaneous papules and nodules were often confined to the injection site, typically palpable, asymptomatic and non-visible, occurring days to months after injection and had a prolonged time course to resolution. See ADVERSE EVENTS for details.
- The kinetics of SCULPTRA resorption in humans has not been determined. In an intradermal implantation study in rabbits all animals had "several relatively large remnants" of injectable PLLA visible at 64 weeks after implantation. The tissue response to injectable PLLA was generally greater than the vehicle or negative plastic controls and was described as a chronic, granulomatous reaction characterized by foreign body giant cells and macrophages. The tissue reaction was confined to the area between particles, did not involve the surrounding tissue and was not unexpected, because it was consistent with the persistent and particle nature of injectable PLLA.
- SCULPTRA should only be used by a physician trained to correct volume deficiencies in patients with human immunodeficiency virus after the physician is fully familiar with the product, product educational materials, and the entire package insert and patient labeling.
- The safety and effectiveness of injecting SCULPTRA: 1) in larger amounts, 2) at different frequencies, 3) at anatomic sites other than those having signs of facial fat loss (lipoatrophy), 4) with different techniques, or 5) at anatomic sites that have had previous other dermal filler injections, have not been evaluated.
- Long-term safety and effectiveness of SCULPTRA beyond two years have not been investigated. A post approval study is being conducted to evaluate the safety and effectiveness of SCULPTRA beyond two years.
- The safety and effectiveness of SCULPTRA for use in the lips has not been evaluated. Do not inject into the red area (vermillion) of the lip.
- SCULPTRA should be used in the deep dermis or subcutaneous layer. Superficial injections may be associated with increased local adverse events such as nodules and papules. Take special care when using SCULPTRA in areas of thin skin. Please refer to PATIENT TREATMENT for injection techniques.
- SCULPTRA injection in the peri-orbital area has not been studied. An increased risk of papules and nodules has been reported in published literature after injections in the periorbital area.
- Safety and effectiveness of SCULPTRA has not been evaluated in patients who are pregnant, lactating, breastfeeding, or under 18 years of age.
- Safety and effectiveness of SCULPTRA has not been evaluated in patients with the following: history of keloid formation, hypertrophic scarring, connective tissue disease, active inflammatory conditions, bleeding disorders, active hepatitis, serious abnormalities in laboratory findings other than CD4 cell count, HIV viral load and lactic acid, disease such as cancer, stroke or myocardial infarction, on any immunosuppressive therapy, and/or with any other prior or concomitant treatment at the SCULPTRA treatment site.
- Safety and effectiveness of SCULPTRA has not been systematically evaluated with local anesthetics, other drugs or devices used during the same treatment session. The safety and effectiveness of the volume ratio of SCULPTRA mixed with local anesthetic or any drug or device has also not been assessed.
- Other filler products should not be directly mixed with SCULPTRA. No studies of interactions of SCULPTRA with drugs or other substances or implants have been made.
- The volume of SCULPTRA injection per surface area has not been assessed.
- It is not known whether SCULPTRA is radiopaque. The microparticles of SCULPTRA may be visible on computer tomography (CT) scans, magnetic resonance imaging (MRI), ultrasound or standard, plain radiography. Patients should be informed that the device may be radiopaque, so that they can inform their health care professionals, including radiologists.
- The safety and effectiveness data from clinical trials of SCULPTRA in non-Caucasians and females with human immunodeficiency virus are limited.
- As with all transcutaneous procedures, SCULPTRA injection carries a risk of infection. Standard precautions to minimize infections associated with injectable materials should be followed.
- As with all injections, patients with coagulation defects or on concurrent anti-coagulant therapy are at increased risk for hematoma formation, bruising and/or bleeding at the injection site.
- As with all invasive procedures, SCULPTRA sessions should be conducted with aseptic technique. 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 are considered contaminated biohazards. Handle and dispose contaminated syringes and needles in accordance with accepted medical practice and applicable local, state and federal requirements.
- The patient should be informed that he or she should minimize exposure of the treatment area to sun and avoid UV lamp exposure 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 SCULPTRA, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if SCULPTRA is administered before the skin has healed completely after such a procedure.
- SCULPTRA vials are for single patient use only. Do not reuse or resterilize the vial. Do not use if the package or vial is opened or damaged.
NUMBER OF PATIENTS WITH TREATMENT-RELATED ADVERSE EVENTS OBSERVED IN
CLINICAL STUDIES WITH TWO-YEAR FOLLOW-UP
|INJECTION PROCEDURE RELATED
|Edema||2 (4%)||2 (7%)||3|
DEVICE-RELATED ADVERSE EVENTS
|Injection site subcutaneous papule*||26 (52%)||9 (31%)||7|
|*Subcutaneous papules refer to lesions of 5 mm or less, typically palpable, asymptomatic and non-visible.|
|**Onset data available from VEGA study only. Duration not noted for subcutaneous papules because most were ongoing at study completion.|
|*** Safety data were collected post hoc for 27 of the patients at approximately two years from study start.|
NUMBER OF PATIENTS WITH TREATMENT-RELATED ADVERSE EVENTS OBSERVED IN
CLINICAL STUDIES WITH ONE-YEAR FOLLOW-UP
|INJECTION PROCEDURE RELATED ADVERSE
|Bruising||1 (1%)||30 (30%)|
|Edema||3 (3%)||17 (17%)|
|Discomfort||19 (19%)||15 (15%)|
DEVICE-RELATED ADVERSE EVENTS
|Injection site subcutaneous papule||6 (6%)||13 (13%)|
The duration of adverse events in Table 2 was not collected. The most common device related effect was the delayed occurrence of subcutaneous papules which were confined to the injection site and were typically palpable, asymptomatic, and non-visible. The study protocols did not include evaluation of treatment for subcutaneous papules, therefore, no information is available on how the papules were treated. In the VEGA study, the average onset of subcutaneous papules was 7 months after initial injection (range 0.3 – 25 months). Subcutaneous papules resolved spontaneously in 6/26 patients (24%) during the study. No information of onset and duration of papules is available from the Chelsea & Westminster study.
Treatment related adverse events, not included in Table 1 & 2, observed in clinical studies with a frequency of less than 5% were: injection site tenderness, injection site lesion, injection site bleeding, injection site induration, injection site infection and fever.
Post Marketing Surveillance
The following adverse events were received from post-marketing surveillance for SCULPTRA and SCULPTRA Aesthetic in the US and outside the US, that were not observed in the clinical trials with SCULPTRA:
allergic reaction, angioedema (Quincke's edema), application site discharge, fatigue, hypersensitivity reaction, hypertrophy of skin, injection site abscess, injection site atrophy, injection site fat atrophy, injection site granuloma (including ectropion), injection site induration, lack of effectiveness, malaise, periorbital nodules, photosensitive reaction, scar and skin discoloration, skin infection (including cellulitis (facial) and staphylococcal infection), skin rash, skin roughness, skin sarcoidosis, telangiectasias, urticaria, visible nodules with or without inflammation or discoloration, injection site reaction, hair breakage, colitis not otherwise specified, brittle nails, aching joints.
Scarring, mostly a non-serious event, has been reported in association with skin discoloration, nodules, lumps, indurations, granulomas, hyperpigmentation, hypertrophic scars, and suspicion of keloid formation. Time to onset ranged from 1 month to 24 months post-Sculptra injection and outcome ranged from ‘improved’ to ‘on-going’ at last contact.
Skin discoloration has been reported as a non-serious event, typically reported in association with lumps and nodules. It has also been reported with blanching and telangiectasias. Time to onset usually ranged from 1 month to 12 months post-injection. Outcome ranged from 'improved' to 'on-going' at last contact.
Serious adverse events have infrequently been reported. The most commonly reported serious adverse events (by MedDRA Preferred Term) were injection site nodule, granuloma, nodule, erythema, pain, inflammation, edema, hypersensitivity and pruritus. Regarding these infrequently reported adverse events the following describes serious adverse events with a frequency greater than 5 reported events:
- Injection site nodules mostly occurred several months post-injection, with time to onset ranging from 1-2 months to 14 months post-last injection. In some cases, the nodules were reported to resolve spontaneously or following treatment with intralesional corticosteroids; others have been described with a prolonged duration of up to 2 years. For those nodules that were larger in size, occurring in difficult anatomical regions (e.g. lower eyelid) or persisted after other treatments such as intralesional corticosteroids failed, surgical excision of the device was required.
- Serious granulomas usually occur several months after injection, in few cases onset was more than 1 year post-injection. While events were reported as granuloma, biopsy confirmation was made on few cases. Treatment ranged from subcision or intralesional corticosteroid with subsequent improvement, to surgical extraction. Of the few granuloma cases that required hospitalization, these were associated with infraorbital use or injection in the lip vermilion. For cases where information was available the patients were recovering following treatment.
- Serious erythema, serious pain, and serious pruritus reported with bruising and heat sensation, were reported within 24 hours post-injection. Treatment included corticosteroids, anti-histamines and/or anti-inflammatories. Events resolved within 7-10 days post-injection without sequelae and with no significant impact on daily life.
- Serious edema has been reported in association with erythema, pain, and heat sensation. The symptoms were mostly temporary, and with no significant impact on the quality of daily life reported. Treatment included corticosteroids, anti-histamines and/or anti-inflammatories. Recovery occurred within 7-10 days without sequelae.
- Serious hypersensitivity reactions have been reported mainly in association with facial swelling and Quincke's edema, with symptoms appearing from 1 day to 1 week post-injection. Patients recovered without sequelae after treatment with intravenous corticosteroids and anti-histamines.
- Serious infections such as subcutaneous abscesses, cellulitis, folliculitis, and methicillin-resistant Staphylococcus aureus at the injection site, have been reported. Time to onset of event ranged from 1 day to one week. Of these cases a few required hospitalization with administration of intravenous antibiotics. All patients recovered or were recovering at the last contact.
Clinical data including skin thickness measurements and serial photographs were collected in four clinical studies.
This was a 96-week, open-label, uncontrolled, single-center study to determine the treatment effects of SCULPTRA on the signs of lipoatrophy of the face in 50 patients infected with human immunodeficiency virus. Patients had a mean age of 45 years (range 33-58), 84% were Caucasian and 98% were male. All patients had little or no adipose tissue in cheek area at baseline, indicating severe facial lipoatrophy (mean adipose thickness of 0.5±0.7 mm, ranging from 0.0 to 2.1 mm).
Injection sessions were conducted at approximately two-week intervals, and the majority (86%) of the patients received four to five injection sessions. Generally, one vial of product was injected intradermally into multiple points of each cheek at each injection session. The quantity of injected product and number of injection sessions depended upon the severity of the facial depression.
The mean increases from baseline in skin thickness are presented in Figure 1 below.
MEAN INCREASES ABOVE BASELINE IN SKIN THICKNESS (MM) OBSERVED IN THE
All patients experienced increases in skin thickness in the treatment area (minimum increase of 2.2 mm noted at Week 8 visit). Statistically significant increases above baseline values of mean skin thickness were noted at all time points (Weeks 8, 24, 48, 72 and 96) during the study. Increases in mean skin thickness changes above baseline persisted for up to 2 years.
Chelsea & Westminster (C&W) Study
This was a 24-week, open-label, single-center, uncontrolled study in 30 human immunodeficiency virus positive patients with facial lipoatrophy. Patients were placed into groups of 12 or 24 weeks of follow-up. Patients had a mean age of 41 (range 32-60), 72% were Caucasian and 93% were male.
All patients received a fixed treatment regimen of three injection sessions conducted at two-week intervals. Each vial of SCULPTRA was reconstituted with 2 mLs of SWFI and 1 mL of 2% lidocaine to give a total volume of 3 mL. Up to 3 mL of the reconstituted product was injected bilaterally into multiple points into the cheek and nasolabial areas.
Baseline skin thickness in the treatment areas ranged from 2.1 to 2.7 mm and are presented in the Table 3 below.
RANGE OF MEAN INCREASES IN SKIN THICKNESS FROM BASELINE
|12 WEEKS AFTER
|24 WEEKS AFTER
|Cheek Areas||3.9 – 5.7 mm||4.9 mm|
|Nasolabial Areas||3.9 – 6.0 mm||4.9 – 5.3 mm|
|Baselines ranged from 2.1 to 2.7 mm; all changes were significant (p<0.001).|
|* Number of patients varies dependent upon which group they were placed.|
Significant changes from Baseline (p<0.001) in mean skin thickness were observed in the areas treated (left and right nasolabial and cheeks) with SCULPTRA in all patients. A mean increase in skin thickness of approximately 4-6 mm was observed twelve weeks after the initiation of treatment for all treated patients.
APEX 002 and Blue Pacific Studies
Data were obtained from two, single-center, open-label, 12-month investigator-initiated studies in human immunodeficiency virus positive patients with facial lipoatrophy. Ninety-nine patients between 31 and 65 years of age were enrolled in each study. The majority of patients were Caucasian males.
Patients were treated with SCULPTRA injections at an interval of approximately 3 to 6 weeks and received up to 6 injection sessions.
The results from these studies are shown in Table 2 and were provided for safety information only.
INDIVIDUALIZATION OF TREATMENT (see also Patient Treatment)
The quantity of SCULPTRA and the number of injection sessions will vary by patient. Treatment for severe facial fat loss typically requires the injection of one vial of SCULPTRA per cheek area per injection session. A typical treatment course for severe facial fat loss involves 3-6 injection sessions, with the sessions separated by two or more weeks. Full effects of the treatment course are evident within weeks to months. The patient should be reevaluated no sooner than two weeks after each injection session to determine if additional correction is needed. Patients should be advised that supplemental injection sessions may be required to maintain an optimal treatment effect.
SCULPTRA is supplied as a sterile freeze-dried preparation for injection in a clear glass vial, which is sealed by a penetrable stopper, covered by an aluminum seal with a flip-off cap. Each carton of SCULPTRA contains two vials of poly-L-lactic acid, sodium carboxymethylcellulose (USP), non-pyrogenic mannitol (USP) NHRIC 8313-1106-02.
IF THE VIAL, SEAL, OR THE FLIP-OFF CAP ARE DAMAGED, DO NOT USE AND CONTACT SANOFI-AVENTIS U.S. LLC AT 1-800-633-1610.
- Sterile Water for Injection (SWFI), USP
- Single-use 5 mL sterile syringe
- Single-use 1-3 mL (depending on physician practitioner preference) sterile syringes (at least 2)
- 18 G sterile needles (at least 2)
- 26 G sterile needles (several should be available)
SCULPTRA is reconstituted in the following way:
1. Remove the flip-off cap from the vial and clean the penetrable stopper of the vial with an antiseptic. If the vial, seal, or flip-off cap are damaged, do not use, and call sanofi-aventis U.S. LLC at 1-800-633-1610.
2. Attach an 18 G sterile needle to a sterile single-use 5 mL syringe.
3. Draw 5 mLs of SWFI into the 5mL syringe.
4. Introduce the 18 G sterile needle into the stopper of the vial and slowly add all SWFI into the vial.
5. Let the vial stand for at least 2 hours to ensure complete hydration; do not shake during this period. SCULPTRA can be stored at room temperature up to 30°C (86°F) during and after hydration. Refrigeration is not required.
6. Product should be gently agitated immediately prior to use. Agitate the vial until a uniform translucent suspension is obtained. A single vial swirling agitator may be used. The reconstituted product is usable within 72 hours of reconstitution. As it is a single use vial, discard any material remaining after use or after 72 hours following reconstitution.
7. Clean the penetrable stopper of the vial with an antiseptic, and use a new 18 G sterile needle to withdraw an appropriate amount of the suspension (typically 1 mL) into a single–use 1-3 mL sterile syringe. Do not store the reconstituted product in the syringe.
8. Replace the 18 G needle with a 26 G sterile needle before injecting the product into the deep dermis or subcutaneous layer. Do not inject SCULPTRA using needles of an internal diameter smaller than 26 G.
9. To withdraw remaining contents of the vial, repeat steps 6 through 8.
1. Patient Counseling.
It is necessary to counsel the patient and discuss the appropriate indication, risks, benefits and expected responses to the SCULPTRA treatment. Advise the patient of the necessary precautions before commencing the procedure.
- Before treatment with SCULPTRA, a patient should be provided patient labeling and completely informed by the treating physician of the intended use, indications for use, as well as the contraindications, warnings and precautions for use, expected correction, and possible side effects and mode of administration of SCULPTRA. Each patient should be informed that the amount of SCULPTRA and the number of injection sessions will depend on the patient's need.
- Patients should be informed that typically, at the end of the injection session, they will experience some degree of swelling due to the water (SWFI) used to reconstitute SCULPTRA and this will give the appearance of a full correction by the end of the injection session.
- Patients should be informed that the injection-related swelling typically resolves in several hours to a few days, resulting in the reappearance of the original contour deficiency.
- Patients should also be informed that the optimal correction after initial injection depends on patient's severity of the facial depression.
- Patients should be informed that, if needed, their physician may utilize a topical or a local anesthetic prior to injecting SCULPTRA.
2. Patient Assessment.
- A complete medical history should be taken to determine if SCULPTRA injection is appropriate. A patient should be informed of the optimal correction that may be expected by that patient, and the number of injection sessions will depend on the severity of facial lipoatrophy.
- During the initial treatment session with SCULPTRA, only a limited correction should be made. In contrast to other dermal fillers, SCULPTRA provides a gradual improvement of the depressed area over several weeks as the treatment effects occur.
3. Patient Preparation. Each injection session is to be conducted with aseptic technique and universal precautions due to the potential for contact with patient body fluids: blood from the injection site. Before injecting SCULPTRA, a treatment plan is determined and the face mapped. The mapping is done using a water soluble pencil. See Section 6 and 7 - Injecting: Threading or Tunneling Technique, Depot Technique.
4. The needle for injections. SCULPTRA should be injected using a 26 G sterile needle. Do not inject with needles with a diameter smaller than 26 G and/or needles that have been bent. To maintain a uniform suspension throughout the procedure, intermittently agitate the product in the syringe. Before initial injection, expel a few drops of SCULPTRA through the attached 26 G needle to eliminate air and to check for needle blockage. If the needle becomes occluded or dull during an injection session replacement is necessary. If clogging occurs, remove the needle, expel a small amount of product, attach a new sterile 26G needle, then expel a few drops of SCULPTRA to eliminate the air and re-check for needle blockage.
5. The depth of injection. SCULPTRA should be injected into the deep dermis or subcutaneous layer. To guide the needle, create a firm needle insertion plane by stretching the skin. Introduce a straight, sterile, bevel-up 26 G needle into the skin at an approximately 30-40 degree angle to the skin and then advance the needle until the desired skin depth is reached. A change in tissue resistance is felt when the needle crosses from the dermis into subcutaneous layer. If the needle is inserted at too shallow (small) an angle or if the needle tip is not sufficiently advanced, then the needle tip may be in the mid or superficial (papillary) dermis, the needle bevel may be visible through the skin. If SCULPTRA is injected too superficially, the injected area will blanch immediately or slightly after injection. If the injected area blanches, remove the needle and massage the area in a circular fashion. In the event that the blanching does not disappear, the patient should not be re-injected.
6. Injecting: Threading or Tunneling
a. Technique. When the needle tip is in the deep dermal or subcutaneous plane, the needle angle should be lowered to 10-20 degrees and the needle should be advanced parallel to the surface of the skin. Before injecting SCULPTRA, always perform a reflux maneuver to avoid intravascular injection. If blood returns to the syringe, the needle is in a blood vessel and should be withdrawn, pressure should be applied to the injected area until bleeding stops and a new syringe should be prepared. If no blood is pulled back into thesyringe, use the threading or tunneling technique, to deposit a thin trail of SCULPTRA by doing a retrograde injection when slowly withdrawing the needle. To avoid deposition in the superficial skin, deposition should be stopped before the needle bevel is visible in the skin.
b. Volume per injection. The maximum volume of SCULPTRA per each individual injection should be limited to 0.1 mL – 0.2 mL, spaced at a distance of 0.5 -1 cm. Note that in areas such as the cheek, approximately 20 injections may be required to cover the targeted area. Avoid overcorrection.
c. Volume per treatment area. The volume of product injected per treatment area will vary depending on the surface area to be treated. Treatment of an entire cheek typically requires injection of one vial of SCULPTRA per cheek per injection session. Multiple injections (typically administered in a grid or cross-hatched pattern) may be required to cover the targeted area. The total number of injections and thus total volume of SCULPTRA injected will vary based on the surface area to be corrected, not on the depth or severity of the deficiency to be corrected. During the initial treatment sessions only a limited correction should be made. In contrast to other dermal fillers, SCULPTRA provides a gradual improvement of the depressed area over several weeks as the treatment effects occur.
7. Injecting: Depot
a. Technique. The depot technique is most appropriate for injections into areas of thin skin at the level of the temples. When using this technique, SCULPTRA is injected as a small bolus. It is injected in the temporal fascia.
b. Volume per injection. The volume of SCULPTRA should be reduced to approximately 0.05 mL/injection. Following each injection, the area should be massaged.
8. Massage during the injection session. The treatment areas should be periodically massaged in a circular fashion after every 3-4 injections to evenly distribute the product.
9. Degree of correction. The depressed area should be under-corrected, never fully corrected or overcorrected (overfilled) during an injection session. Under- correction of the treatment area allows for gradual improvement of the contour deficiency as the SCULPTRA effect occurs over several weeks between assessment and possible next injection session. Typically, patients will experience some degree of edema associated with the injection procedure itself, which will give the appearance of a full correction by the end of the injection session (within about 30 minutes). The patient should be informed that the injection-related edema typically resolves in several hours to a few days, resulting in the ‘reappearance’ of the original contour deficiency.
10. Post-treatment care. Immediately following an injection session with SCULPTRA, redness, swelling, and/or bruising may appear in the treatment area. Refer to ADVERSE EVENTS for details of the incidence and severity of adverse event observed immediately post-injection during the clinical trial. After the injection session, an ice pack (avoiding any direct contact of the ice with the skin) should be applied to the treated areas in order to reduce edema and/or bruising. To help SCULPTRA distribute evenly in the contour deficiency, it is important to manually massage in a circular fashion the treatment area for a minimum of 2 minutes. A facial moisturizer should be used to perform the massage. The patient should periodically massage the treatment areas for five minutes, five times per day for five days after the injection session to promote a natural-looking correction.
Early occurrence of subcutaneous nodules at the injection site (within 3 to 6 weeks after the treatment) may be minimized by adhering to proper dilution and injection techniques (e.g., avoiding superficial injections or over-correction). In addition, massaging the treatment area to ensure proper distribution of the product may also minimize the appearance of nodules. Nodules usually resolve spontaneously. However, as reported in published literature, some nodules may require medical treatment such as subcision (break-up of nodules with sterile saline solution), and delayed occurrence of subcutaneous nodules at the injection site (usually will manifest within 3 to 4 months after the treatment) may require treatment such as intralesional injections of corticosteroids, subcision and/or excision.
11. Treat, Wait, Assess. During the first injection session with SCULPTRA, only a limited correction should be made. The contour deficiency should be under- corrected, never fully corrected or overcorrected (overfilled) during any injection session. Re-evaluate the patient no sooner than two weeks after the injection session to determine if additional correction is needed. The patient should be advised before and after an injection, that typically at the end of the injection session, it is expected to experience some degree of swelling associated with the injection procedure itself. This will give the appearance of a full correction by the end of the injection session and this injection-related swelling typically resolves in several hours to a few days. For this reason, the original contour deficiency may initially reappear, but the deficiency is expected to gradually improve within several weeks of SCULPTRA injection as the effect occurs. The patient should be advised of the potential need for additional injection sessions at the first consultation.
- To report any adverse reactions, call sanofi-aventis U.S. LLC at 1-800-633-1610.
- Within the first 24 hours, an ice pack (avoiding any direct contact of the ice with the skin) should be applied to the treatment area to reduce swelling and bruising. SCULPTRA may cause redness, swelling, or bruising when first injected into the skin, typically resolving in hours to one week. Hematoma may also occur, typically resolving in hours to about two weeks. Worsening or prolonged symptoms or signs should be reported to the health care provider. The original skin depression may initially reappear, but the depression should gradually improve within several weeks as the treatment effect of SCULPTRA occurs. The health care provider will assess the need for additional SCULPTRA injection sessions after two or more weeks.
- Massage in a circular fashion the treated areas for 5 minutes, 5 times per day for 5 days following any injection session, according to the physician's advice.
- Treatment with SCULPTRA can result in small papules in the treated area. These subcutaneous papules are typically not visible and asymptomatic and may be noticed only upon pressing on the treatment area. However, visible nodules, sometimes with redness or color change to the skin, have been reported. Patients should report these events and any side effects to their health care provider.
- Make-up may be applied a few hours post-treatment if no complications are present (e.g. open wounds, bleeding, redness and swelling).
- Patients should minimize exposure of the treatment area to excessive sun and UV lamp exposure until any initial swelling and redness has resolved. Patients should be informed about appropriate sunscreen protection according to the physician's advice.
ANY SIDE EFFECTS OR PRODUCT COMPLAINTS SHOULD BE REPORTED TO:
sanofi-aventis U.S. LLC
Bridgewater, NJ USA
Prescribing Information as of September 2009.
a business of sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
©2009 sanofi-aventis U.S. LLC
Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed physician or properly licensed practitioner.
A PATIENT'S GUIDE TO TREATMENT WITH SCULPTRA®
(injectable poly-L-lactic acid)
Please review this information carefully before beginning your SCULPTRA Treatment.
This guide is intended to help you become familiar with SCULPTRA use, as well as the expected correction, method of injection, post-injection skin care and possible side effects. You may request additional information such as the product label that further describes SCULPTRA and its clinical data from your physician. This information is also available on www.sculptra.com.
This information is not meant to replace information provided by your healthcare provider. You should always ask your healthcare provider about your treatment and care.
Anesthetic: A substance that causes loss of feeling or awareness. A topical or local anesthetic is a drug that causes temporary loss of feeling in a part of the body.
Antiseptic: An agent that kills bacteria or prevents or slows growth of germs.
Biocompatible: A material that does not harm the body.
Biodegradable: A material that can be broken down by the body.
Collagen: The most common protein found in the body. Collagen is used to form a framework to support cell and tissue.
Hypersensitivity: undesirable, discomfort producing reaction; or an allergic reaction.
Injection: Product delivery at the location of a hollow needle tip beneath the surface of the skin.
Induration: Any hardening or thickening of tissue or skin.
Keloid formation/Hypertrophic scarring: An overgrowth of scar tissue at the site of a skin injury. Keloids/hypertrophic scarring may occur around surgical cuts, traumatic wounds, vaccination sites, burns, or minor scratches. Hypertrophic scarring commonly resolves during the first year after injury; keloid formation most commonly does not resolve.
Lipoatrophy: The loss of body fat that is normally under the skin.
Nodule: Lump under the surface of the skin that is less than 5 mm and not visible, but can be felt when pressed.
Palpable: Able to be touched and felt.
Papule: Lump under the surface of the skin that is less than 5 mm and not visible, but can be felt when pressed.
Patient label: Product information for patients
Peri-orbital: Around the eye.
Poly-L-lactic acid: A man-made lactic acid polymer that is biocompatible and biodegradable and has been used for over 25 years in dissolvable stitches, soft tissue implants and other implants.
Side effect: An unwanted event caused by use of the product.
WHAT IS SCULPTRA?
SCULPTRA is a sterile, injectable, biocompatible, biodegradable material that is made of very small particles of a synthetic polymer known as "poly-L-lactic acid" (PLLA), carboxymethylcellulose (USP), non-pyrogenic mannitol (US) and sterile water for injection (USP). While the time needed for SCULPTRA to resorb in humans is not known, in rabbits, particles were visible at over one year after injection.
WHO MIGHT BENEFIT FROM TREATMENT WITH SCULPTRA?
SCULPTRA is intended for restoration and/or correction of the signs of facial fat loss (lipoatrophy) in people with human immunodeficiency virus. Your healthcare provider can help you determine if you might benefit from SCULPTRA and the optimal correction expected for you.
WHO SHOULD NOT USE SCULPTRA?
You should not use SCULPTRA if you:
- Are allergic to any ingredient of SCULPTRA: "poly-L-lactic acid" (PLLA), carboxymethylcellulose (USP) or non-pyrogenic mannitol (USP).
- Previously had or have risks factors for hypertrophic scarring or keloid formation.
WHAT SHOULD I BE AWARE OF BEFORE RECEIVING SCULPTRA INJECTIONS?
In addition to the other information contained in this guide, you should be aware of the following:
- Your healthcare provider needs to know your complete medical history to determine if SCULPTRA injection is appropriate. Tell your healthcare provider your complete medical history and if you have an active skin inflammation, an infection or difficulty healing in or near the treatment area.
- Other filler products should not be directly mixed with SCULPTRA.
- SCULPTRA should not be injected into sites with active inflammation (e.g., cysts, pimples, rashes or hives). Injection should be deferred until any inflammation has resolved.
- As with all injection procedures, SCULPTRA injection carries a risk of infection.
- As with all injections, people with coagulation defects or on concurrent anti-coagulant therapy are at increased risk for hematoma formation, bruising and/or bleeding at the injection site. If you are taking blood thinners or medications that may interfere with clotting of the blood, such as aspirin, you might be more likely to have bruising or bleeding at the injection site.
- SCULPTRA has not been systematically evaluated in clinical trials for:
- Long term safety and effectiveness of SCULPTRA beyond 2 years
- Subjects who are pregnant, lactating, breast feeding, or under 18 years of age. Product use in pediatric patients is not recommended.
- Subjects with the following: history of keloid formation, hypertrophic scarring, connective tissue disease, active inflammatory conditions, bleeding disorders, active hepatitis, serious abnormalities in laboratory findings other than CD4 cell count, HIV viral load and lactic acid, disease such as cancer, stroke or myocardial infarction, on any immunosuppressive therapy, and/or with any other prior or concomitant treatment at the SCULPTRA treatment site.
- Use with local anesthetics, other drug or device use during the same treatment session. No studies of interactions of SCULPTRA with drugs or other substances or implants have been made.
- Use in areas of the body other than the face.
- An increased risk of papules and nodules has been reported in published literature after injections in the periorbital area.
- Safety and effectiveness data from clinical trials of SCULPTRA in non-Caucasians and women with human immunodeficiency virus are limited.
- After treatment with SCULPTRA, you should minimize exposure of the treatment area to sun and avoid UV lamp exposure 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 SCULPTRA, there is a possible risk of increased inflammatory reaction at the SCULPTRA implant site. This also applies if SCULPTRA is administered before the skin has healed completely after such a procedure.
- SCULPTRA should not be injected into the red area of the lip or the skin near the eyes (e.g., eyelid and eyelid folds).
- It is unknown whether SCULPTRA may be seen during radiologic imaging of your face. If radiologic imaging of your face such as computer tomography (CT) or magnetic resonance imaging (MRI) is to be performed, you should notify the physician about the location of your previous SCULPTRA injection.
HOW DOES SCULPTRA WORK?
SCULPTRA is injected below the surface of the skin in the area of fat loss. SCULPTRA provides an increase in skin thickness. SCULPTRA will not correct the underlying cause of the facial fat loss, but will help improve the appearance by increasing skin thickness in the treated area. SCULPTRA works by initially filling with small particles of poly-L-lactic acid (PLLA) beads. As the particles are broken down by the body, beads biodegrade the body and may produce new collagen where SCULPTRA is injected. Visible results appear within the first few treatment sessions.
WHAT WERE THE RESULTS OF THE CLINICAL STUDIES CONDUCTED ON SCULPTRA?
Four clinical studies were conducted to evaluate Sculptra in patients with HIV associated facial lipoatrophy. The studies varied in the number of treatment sessions (3 to 6 injection sessions), the time between treatment sessions (2 to 6 week intervals), the quantity of Sculptra injected (3 mL to 1 vial, depending on the study design and the severity of the facial depression) and the length of time patients were followed in the study (96 weeks, 24 weeks, 12 months). A total of 278 patients received treatment with Sculptra across the 4 studies. In two of the studies, increases in skin thickness from baseline was provided. In the first study, in patients with severe facial lipoatrophy, an increase in skin thickness was observed starting at week 8 (average of 5.2 mm) through to Week 96 (average of 7.0 mm). In the second study, an increase in skin thickness was observed in 27 patients at 12 weeks (ranging from 3.9 to 6.0 mm in the cheek area and nasolabial areas) and in 14 patients at 24 weeks (ranging from 4.9 to 5.3 mm in the cheek area and nasolabial areas). Safety from the 4 studies was evaluated by comparing the number and severity of side effects observed during the studies. Side effects are summarized in the table 1 below.
|NUMBER OF PATIENTS WITH TREATMENT-RELATED SIDE EFFECTS OBSERVED
IN CLINICAL STUDIES WITH ONE TO TWO YEARS OF FOLLOW-UP
|INJECTION PROCEDURE RELATED
DEVICE-RELATED SIDE EFFECTS
|Small lumps under the skin||54 (19%)|
|* Occasionally accompanied with redness|
The most common side effects with the use of SCULPTRA include injection-related side effects at the site of the injection, such as bleeding, tenderness or pain, redness, bruising, or swelling. These side effects generally last, on average, 3 to 17 days.
One possible delayed side effect with SCULPTRA can be small lumps under the skin in the treated area. These small lumps may not be visible, and you may notice them only when you press on the treated skin. These lumps tend to happen within the first six to twelve months after the first treatment. Occasionally, these lumps go away on their own. Visible lumps, sometimes with redness or color change to the treated area, have also been reported. As with all procedures that involve an injection through the skin, there is a risk of infection.
Report any side effects to your health care provider.
WHAT ADVERSE EVENTS HAVE BEEN REPORTED THROUGH VOLUNTARY POST-MARKETING SURVEILLANCE OF SCULPTRA AND SCULPTRA AESTHETIC USE IN AND OUTSIDE OF THE US?
The most commonly reported serious adverse events were lumps or nodules at the injection site, delayed swollen lumps (granulomas), redness, pain, inflammation, swelling, hypersensitivity and itching. The following events were reported more than 5 times:
- Injection site nodules mostly occurred several months after injection, starting from 1-2 months to 14 months after last administration. In some cases, the nodules went away on their own or after treatment with corticosteroid injections; other nodules lasted up to 2 years. In some cases surgery was required to remove the nodules.
- Serious delayed swollen lumps (granulomas) were reported from several months after injection to more than 1 year after injection. These were treated with corticosteroid injections or surgical procedures. Some cases involving the area under the eyes (infraorbital) or injection in the red area of lips (lip vermilion) required hospitalization. For cases where information was available, the patients were recovering following treatment.
- Serious redness, pain, itching, bruising and heat sensation, were reported within 24 hours after injection. Treatment included corticosteroids, anti-histamines and/or anti-inflammatories. These went away within 7-10 days.
- Serious swelling was reported following injection. Treatment included corticosteroids, anti-histamines and/or anti-inflammatories. Swelling went away within 7-10 days.
- Serious hypersensitivity reactions have been reported, including severe facial swelling (Quincke's edema), with symptoms appearing from 1 day to 1 week after injection. Patients recovered without complication after treatment with intravenous corticosteroids and antihistamines.
- Serious infections at the injection site have been reported, starting from 1 day to one week after injection. Of these cases a few required hospitalization for intravenous antibiotics. All patients recovered or were recovering at the last contact.
Other events that were reported included: application site discharge, fatigue, hypertrophy of skin, injection site atrophy, injection site hardness (induration), lack of effectiveness, malaise, photosensitive reaction, scar, skin discoloration, skin rash, skin roughness, skin disease inflammation (skin sarcoidosis), skin whitening at the injection site, dilated small blood vessels (telangiectasias), hives (urticaria), visible lumps with or without inflammation or discoloration, injection site reaction, hair breakage, colitis, brittle nails and aching joints.
ARE SKIN TESTS NEEDED BEFORE TREATMENT WITH SCULPTRA?
No skin testing is required prior to use in patients with skin that heals normally.
HOW OFTEN ARE SCULPTRA TREATMENTS GIVEN AND HOW MANY TREATMENTS ARE REQUIRED?
Your health care provider will decide with you the number of treatment sessions and the amount of SCULPTRA you will need at each treatment session. Patients with severe facial fat loss may require three to six treatment sessions. Touch-up treatments may be needed to maintain the desired effect. Your health care provider should see you two or more weeks after each treatment to assess whether you need additional treatment.
HOW LONG DO TREATMENT EFFECTS LAST?
Treatment effects will differ for each person. In a clinical study the treatment results lasted for up to 2 years after the first treatment session, in most patients. Touch-up treatments may be needed to maintain the desired effect. A post approval study is being conducted to determine the long-term effects beyond two years.
DO INJECTIONS OF SCULPTRA HURT?
As with any injection, to decrease pain during injection, a topical or local anesthetic may be applied to the injection area before injecting SCULPTRA. In the clinical studies, 13% of treated patients reported pain.
WHAT CAN I EXPECT TO HAPPEN AT A TREATMENT SESSION?
Your health care provider will answer all of your questions and ask about your medical history to determine if SCULPTRA injection is appropriate for you. Tell your healthcare provider about all the medicines you are taking, even over the counter medicines or treatments. You and your healthcare provider will determine if a topical or local anesthetic is needed.
- To prepare for an injections session, all make-up should be removed.
- The area to be injected will be cleaned with an antiseptic.
- SCULPTRA will be injected in small amounts into the skin using a fine needle. Multiple injections will be needed.
- After injection, the treated area should be massaged to distribute the product evenly.
- An ice pack should be applied to the treatment area to help reduce swelling unless otherwise directed by your healthcare provider.
WHAT CAN I EXPECT AFTER TREATMENT?
Immediately following a treatment session with SCULPTRA, redness, swelling, pain, bruising or all of these signs can happen in the treatment area. These signs usually go away in a few hours to a few days. Some have been known to last up to 17 days. Your health care provider will give you specific post-treatment care instructions. Some specific instructions you should follow after treatment are:
- Massage the treated area for 5 minutes 5 times per day for 5 days after your treatment
- Within the first 24 hours after treatment, apply ice or an ice pack wrapped in cloth (avoid putting ice directly on your skin) to the treatment area to help reduce swelling.
- Avoid sun and UV lamp exposure until swelling and redness have disappeared
- Report any worsening or longer-lasting signs or symptoms to your healthcare provider. As with any injectable filler, you can expect injection-related side effects, such as bleeding, tenderness or pain/discomfort, redness, bruising, or swelling. These side effects generally resolve within a few days. See table 1 in section "What are the results of the clinical studies conducted on SCULPTRA?" above.
HOW QUICKLY CAN I GET BACK TO MY DAILY ACTIVITIES?
Most patients are able to get back to their activities immediately following treatment.
WHEN WILL I BE ABLE TO APPLY MAKE-UP AFTER TREATMENT?
Make-up may be applied a few hours after treatment if there are no complications such as open wounds or bleeding.
WHAT ARE MY OTHER OPTIONS FOR TREATMENT?
Consult with your physician to determine the options available to you for treatment.
FOR FURTHER QUESTIONS AND INFORMATION, OR TO REPORT ANY SIDE EFFECTS, PLEASE CALL SANOFI-AVENTIS AT 1-800-633-1610
Patient Prescribing Information as of September 2009.
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