Poly-L-Lactic Acid

Hypersensitivity to poly-L-lactic acid or any component of the formulation; history or susceptibility to hypertrophic scarring or keloid formation

Facial fat loss (lipoatrophy) (Sculptra): Intradermal or SubQ: ~0.05-0.2 mL per individual injection depending on technique used; ~20 injections may be needed per cheek. Treatment should be individualized. Separate treatments by ≥2 weeks. Typical course involves 3-6 treatments. Supplemental injections may be needed. Do not overfill contour deficiency. For patients with severe facial fat loss, the average treatment requires ~1 vial per cheek area per treatment.

Facial wrinkles (Sculptra Aesthetic): Intradermal: 0.1 to 0.2 mL per individual injection to a maximum of 2.5 mL per nasolabial fold as a single treatment; may repeat treatment at ≥3 week intervals up to 4 times

For injection into deep dermis or subcutaneous layer using tunneling, threading, or depot technique. Avoid intravenous injection. Space injections 0.5 to 1 cm apart. Administer using 26 gauge needle; do not bend needle. Occasionally agitate syringe during session to maintain a uniform suspension. Eliminate air prior to initial injection. Stretch skin prior to inserting needle. Massage treatment area in a circular motion after every 3 to 4 injections and for ≥2 minutes at the end of the treatment session to evenly distribute. Do not fully correct or overcorrect. Local or topical anesthetic may be used prior to injecting. See prescribing information for detailed administration technique.

Prior to reconstitution, store at room temperature, up to 30°C (86°F); do not freeze. Upon reconstitution, store for up to 72 hours at 5°C to 30°C.

There are no known significant interactions.

Reproduction studies have not been conducted. Safety for use in pregnant women has not been established.

• SCULPTRA should only be used by health care providers with expertise in the correction of volume deficiencies in patients with human immunodeficiency virus after fully familiarizing themselves with the product, the product educational materials, and the entire package insert.
• SCULPTRA vials are for single patient use only. Do not reuse or resterilize the vial. Do not use if package or vial is opened or damaged.
• Long-term safety and effectiveness of SCULPTRA beyond two years have not been investigated. Dermik is conducting a post approval study to evaluate the safety and effectiveness of SCULPTRA beyond two years.
• SCULPTRA should be used in the deep dermis or subcutaneous layer. Avoid superficial injections. Special care must be taken when using SCULPTRA in areas of thin skin. Refer to PATIENT TREATMENT for instructions regarding injection techniques.
• Safety and effectiveness of treatment in the periorbital area have not been established.
• As with all transcutaneous procedures, SCULPTRA injection carries a risk of infection. Standard precautions associated with injectable materials should be followed.
• As with all injections, patients treated with anti-coagulants may run the risk of a hematoma or localized bleeding at the injection site.
• Universal precautions must be observed when there is a potential for contact with patient body fluids. The injection session must be conducted with aseptic technique.
• After use, treatment syringes and needles may be potential biohazards. Handle accordingly and dispose of in accordance with accepted medical practice and applicable local, state and federal requirements.
• The safety of SCULPTRA for use during pregnancy, in breastfeeding females or in patients under 18 years has not been established.
• No studies of interactions of SCULPTRA with drugs or other substances or implants have been made.
• The safety and effectiveness data from clinical trials of SCULPTRA in non-Caucasians and women with human immunodeficiency virus are limited. Dermik will conduct a post approval study in non-Caucasians and women with human immunodeficiency virus.
• The safety of using SCULPTRA in patients with increased susceptibility to keloid formation and hypertrophic scarring has not been studied. Dermik will conduct a post approval study to determine the likelihood of keloid formation and hypertrophic scars in patients with human immunodeficiency virus receiving SCULPTRA injections.
• The patient should be informed that he or she should minimize exposure of the treatment area to excessive sun and UV lamp exposure until any initial swelling and redness has resolved.

ADVERSE EVENTS

Adverse event data from four clinical studies that included 277 patients are summarized in Tables 1 & 2 below.

The duration of the adverse events in Table 2 was not collected. The most common device related adverse 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.

The following adverse events, which were not observed in the clinical studies, were detected from post-marketing surveillance outside of the US and literature reports: visible nodules with or without inflammation or dyspigmentation, malaise, injection site abscess, allergic reaction, injection site atrophy, Quincke's edema, injection site fat atrophy, photosensitive reaction, fatigue, injection site granuloma, hypersensitivity reaction, skin rash, skin roughness, lack of effectiveness, injection site reaction, hypertrophy of skin, hair breakage, colitis not otherwise specified, brittle nails, application site discharge, angioedema, aching joints, ectropion, and telangiectasias.

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.

COMPOSITION OF SCULPTRA

The final composition of SCULPTRA consists of poly-L-lactic acid, sodium carboxymethylcellulose (USP), non-pyrogenic mannitol (USP), sterile water for injection (USP).

NHRIC 8313-1106-02

INSTRUCTIONS FOR USE

Reconstitution

The following supplies are used with SCULPTRA but are to be provided by the end-user:

• 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)
• Antiseptic

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 Aventis Pharmaceuticals Inc. at 1-800-633-1610.
2. Attach an 18 G sterile needle to a sterile single-use 5 mL syringe.
3. Draw 3-5 mLs of SWFI into the 5 mL 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[ordm ]C (86[ordm ]F) during and after hydration. Refrigeration is not required.
6. After waiting at least 2 hours, agitate the vial until a uniform translucent suspension is obtained. A single vial swirling agitator may be used. Product should be agitated immediately prior to use. The reconstituted product is usable within 72 hours of reconstitution. 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.

Patient Treatment

1. Patient Assessment . Before treatment with SCULPTRA , the patient should be informed completely of the indications, contraindications, warnings, precautions for use, possible side effects and mode of administration of SCULPTRA . A complete medical history should be taken to determine if the treatment is appropriate. Patients should be informed that more than one injection session is typically necessary to achieve the desired results.
2. Patient Preparation . As with all injectable products, universal precautions must be observed when there is a potential for contact with patient body fluids. The injection session must be conducted with aseptic technique.
3. The needle for injections . SCULPTRA should be injected using a 26 G sterile needle. Do not inject with needles smaller than 26 G and do not bend the needle. Agitate the product in the syringe as needed to maintain a uniform suspension throughout the procedure. Before injecting, expel some drops of the product from the prepared syringe with 26 G needle attached to eliminate air and to check for needle blockage. If the 26 G needle becomes occluded or dull during an injection session replacement may be necessary. Draw a small amount of air into the syringe between needle changes to assist in removing clogged particles.
4. The dermal plane . SCULPTRA should be injected into the deep dermis or subcutaneous layer. In order to control the injection depth of SCULPTRA , stretch/pull the skin opposite to the direction of the injection to create a firm injection surface. The 26 G sterile needle, bevel up, should be introduced into the skin at an angle of approximately 30-40 degrees, until the desired skin depth is reached. A change in tissue resistance is evident when the needle traverses the dermal-subcutaneous junction. If the needle is inserted at too shallow an angle [i.e., into the mid or superficial (papillary) dermis] the bevel of the needle may be visible through the skin. If product is injected too superficially it will be evident as immediate or slightly delayed blanching in the injected area. If this occurs, the needle should be removed and the treatment area gently massaged.
5. Injecting: Threading or Tunneling
   
   1. Technique . When the appropriate dermal plane is reached, the needle angle should be lowered to advance the needle in that dermal plane. Prior to depositing SCULPTRA in the skin, a reflux maneuver should be performed to assure that a blood vessel has not been entered. Using the threading or tunneling technique, a thin trail of SCULPTRA should then be deposited in the tissue plane as the needle is withdrawn. To avoid deposition in the superficial skin, deposition should be stopped before the needle bevel is visible in the skin.
   2. Volume per injection . The volume of SCULPTRA should be limited to approximately 0.1 mL-0.2 mL per each individual injection. Note that in areas such as the cheek, approximately 20 injections may be required to cover the targeted area.
   3. 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.
6. Injecting: Depot
   
   1. Technique . The depot technique is most appropriate for injections into areas of thin skin at the level of the upper zygoma or temples. When using this technique, SCULPTRA is injected as a small bolus. For the upper zygoma it is injected under the orbicularis oculi muscle. For the temples, it is injected in the temporal fascia.
   2. Volume per injection . The volume of SCULPTRA should be reduced to approximately 0.05 mL/injection. Following each injection, the area should be massaged.
7. Massage during the injection session . The treatment areas should be periodically massaged during the injection session to evenly distribute the product.
8. Degree of correction . The depressed area should never be overcorrected (overfilled) in an injection session. Limited correction of the treatment area allows for the gradual improvement of the depressed area over several weeks as the treatment effect occurs. 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.
9. Post-treatment care . Immediately following an injection session with SCULPTRA , redness, swelling, and/or bruising may be noted in the treatment area. Refer to ADVERSE EVENTS for details. After the injection session, an ice pack (avoiding any direct contact of the ice with the skin) should be applied to the treatment area in order to reduce swelling. It is important to thoroughly massage the treatment area to evenly distribute the product. The patient should periodically massage the treatment area for several days after the injection session to promote a natural-looking correction.
10. Treat, Wait, Assess . During the first injection session with SCULPTRA , only a limited correction should be made. Do not overcorrect (overfill). The patient should be evaluated no sooner than two weeks after the injection session to determine if additional correction is needed. The original skin depression may initially reappear, but the depression should gradually improve within several weeks as the treatment effect of SCULPTRA occurs. The patient should be advised of the potential need for additional injection sessions at the first consultation.

PATIENT INSTRUCTIONS

It is recommended that the following information be shared with patients:

• To report any adverse reactions, call Aventis Pharmaceuticals Inc. 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. 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 the treatment area daily, for several days following any injection session.
• Treatment with SCULPTRA can result in small papules in the treatment 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 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.

STORAGE

SCULPTRA can be stored at room temperature, up to 30°C (86[ordm ]F).

DO NOT FREEZE.

Refrigeration is not required.

STERILITY

Each vial of SCULPTRA is packaged for single-use only. Do not resterilize.

IF THE VIAL, SEAL, OR THE FLIP-OFF CAP ARE DAMAGED, DO NOT USE AND CONTACT AVENTIS PHARMACEUTICALS INC. AT 1-800-633-1610.

Rx only.

ANY SIDE EFFECTS OR PRODUCT COMPLAINTS SHOULD BE REPORTED TO:

Aventis Pharmaceuticals Inc.

Bridgewater, NJ USA

1-800-633-1610

Pat. No. US 6,716,251

Prescribing Information as of August 2004.

Manufactured for:

Dermik Laboratories

A Division of Aventis Pharmaceuticals Inc.

1050 Westlakes Drive

Berwyn, PA 19312

USA

1-800-633-1610

Produced by:

Gruppo Lepetit S.p.A. 20020 Lainate, Italy

©2004 Dermik Laboratories

A PATIENT'S GUIDE TO TREATMENT WITH SCULPTRA™

SCULPTRA™

injectable poly-L-lactic acid

GLOSSARY

Anesthetic: A substance that causes loss of feeling or awareness. A topical or local anesthetic 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: Able to be broken down by the body.

Induration: Any hardening or thickening of tissue or skin.

Keloids: An overgrowth of scar tissue at the site of a skin injury. Keloids may occur around surgical cuts, traumatic wounds, vaccination sites, burns, or minor scratches.

Lipoatrophy: The loss of body fat.

Palpable: Able to be touched and felt.

Poly-L-lactic acid: A synthetic material that is biocompatible and bioabsorbable and has been used for over 25 years in dissolvable stitches, soft tissue implants and other implants.

Side effect: An undesirable event caused by use of the product.

Synthetic: "man-made."

BACKGROUND INFORMATION

WHAT IS SCULPTRA?

SCULPTRA is a synthetic injectable material known as "poly-L-lactic acid." Poly-L-lactic acid is a biocompatible, biodegradable material that has been widely used for many years in dissolvable stitches, soft tissue implants, and other types of implants.

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.

WHO SHOULD NOT USE SCULPTRA?

Talk to your health care provider about your medical history when deciding on treatment options.

You should not use SCULPTRA if:

· you are allergic to any ingredient of SCULPTRA .

ARE SKIN TESTS NEEDED BEFORE TREATMENT WITH SCULPTRA?

No skin testing is required prior to use.

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. Visible results appear within the first few treatment sessions.

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.

ARE THE RESULTS FROM SCULPTRA IMMEDIATE?

No. At your first treatment visit it may appear that SCULPTRA worked immediately. That is because of swelling from the injections and the water used to dilute SCULPTRA . In a few days, when the swelling goes down and the water is absorbed by your body, you may look as you did before your treatment. SCULPTRA takes time to gradually correct the depression in your skin. Your health care provider will see you again in a few weeks to decide if you need more SCULPTRA injections.

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.

HOW OFTEN ARE TREATMENTS GIVEN?

Your health care provider will see you two or more weeks after each treatment to assess whether you need additional treatments.

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. Dermik is studying the long-term effects beyond two years.

DO INJECTIONS OF SCULPTRA HURT?

As with any injection, injections with SCULPTRA may hurt. SCULPTRA is injected in small amounts using a very fine needle. Your health care provider may apply a topical or local anesthetic.

WHAT CAN I EXPECT TO HAPPEN AT A TREATMENT SESSION?

Your health care provider will answer all of your questions and prepare you for the treatment.

• Make-up should be removed.
• The area where the injections will be given will be cleaned with an antiseptic.
• You and your health care provider will determine if a topical or local anesthetic is needed.
• SCULPTRA will be injected in small amounts into the skin using a very fine needle. Multiple injections will be needed.
• An ice pack should be applied to the treatment area to help reduce swelling.
• After the treatment session, the area should be thoroughly massaged to disribute the product evenly.

WHAT ARE THE POSSIBLE SIDE EFFECTS OF TREATMENT WITH SCULPTRA?

Talk to your health care provider about the possible side effects of SCULPTRA .

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 bumps under the skin in the treated area. These small bumps may not be visible, and you may notice them only when you press on the treated skin. These bumps tend to happen within the first six to twelve months after the first treatment. Occasionally, these bumps go away on their own. Visible bumps, 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.

SHOULD I TELL MY HEALTHCARE PROVIDER WHAT MEDICATIONS I AM TAKING?

Yes. You should tell your healthcare provider about all the medicines you are taking, even over the counter medicines or treatments. 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. There have been no studies of possible interactions between SCULPTRA and drugs or other substances or implants. Talk to your health care provider about your medical history when deciding on treatment options.

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. You should massage the treated area (a few times each day) for several days after the treatment session. Within the first 24 hours after treatment, an ice pack should be applied for a few minutes at a time to the treatment area to help reduce swelling. Wrap the ice in a cloth and avoid putting ice directly on your skin. Avoid excessive sun and UV lamp exposure until any initial swelling and redness has resolved.

Report any worsening or longer-lasting symptoms or signs to your health care provider.

HOW QUICKLY CAN I GET BACK TO MY DAILY ACTIVITIES?

Most patients feel comfortable going back to their normal activities following treatment.

WHEN WILL I BE ABLE TO APPLY MAKE-UP AFTER TREATMENT?

Make-up may be applied a few hours after treatment if no complications are present (for example, open wounds or bleeding).

ADDITIONAL INFORMATION

What are my other options for treatment?

At present there are no other medical devices for restoration and/or correction of facial fat loss (lipoatrophy) in people with human immunodeficiency virus.

Prescribing Information as of August 2004.

Dermik Laboratories

A Division of Aventis Pharmaceuticals Inc.

1050 Westlakes Drive

Berwyn, PA 19312

Telephone: 1-800-633-1610