Poly-L-lactic acid, also known as PLLA, is the main ingredient of Sculptra, also known as New-Fill. Sculptra is a powder that is mixed with water and then injected into the skin. Sculptra belongs to the class of medicines called dermal fillers. Injecting Sculptra into facial skin may give it a firmer, fuller appearance.
PLLA is used in many medical products such as stitches and screws used to repair broken bones. In Europe, Sculptra is called New-Fill and has been used by more than 100,000 people to treat wrinkles and scars.
HIV/AIDS-Related Uses
PLLA was approved by the FDA on August 3, 2004, for the treatment of facial fat loss (also called facial lipoatrophy). It continues to be studied for this use. Facial lipoatrophy is a condition in which people lose fat in their faces, especially in their cheeks and around their eyes and temples. People with HIV who take anti-HIV drugs may develop lipoatrophy.PLLA is injected into the skin in areas where fat has been lost. It causes the skin to thicken, improves appearance of folds and sunken areas, and hides the fat loss. For most people who participated in PLLA clinical studies, the effects of treatment lasted for up to 2 years after the first treatment session.This medicine does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.
Dosage Form/Administration
PLLA comes as a powder that is mixed with sterile water and then injected into the skin. Only a health care provider with special training should inject PLLA. Patients often need three to five injections of PLLA over the course of several weeks to achieve a visible effect.
Contraindications
Individuals should tell a doctor about any medical problems before using this medicine.
Possible Side Effects
Along with its desired effects, PLLA can cause some unwanted effects; not all of these effects are known at this time. Serious side effects have been rare and include lightheadedness and faintness, swelling of nodules developed under the skin, temporary numbing of the face, and severe allergic reaction. Individuals should tell a doctor if they have any of these side effects.Less serious side effects include redness, swelling, and bruising in the area of the injection. Many patients have developed small nodules in the skin where PLLA was injected. The nodules are not visible and do not hurt. Individuals should tell a doctor if these side effects continue or are bothersome.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Poly-L-lactic acid.
Manufacturer Information
Poly-L-lactic acid
Dermik Laboratories, Inc.
1050 Westlakes Dr.
Berwyn, PA 19312
Phone: 484-595-2700
Fax: 484-595-2733
Sculptra
Dermik Laboratories, Inc.
1050 Westlakes Dr.
Berwyn, PA 19312
Phone: 484-595-2700
Fax: 484-595-2733
Last Updated: January 23, 2007
Drug Description
Poly-L-lactic acid (PLLA) is a biocompatible, biodegradable, and immunologically inert synthetic polymer from the alpha-hydroxy-acid family. Microparticles of PLLA are the active ingredient in Sculptra, the injectable implant used for treatment of facial atrophy. [1] [2]
References
[1] AIDS 2003 Nov 21;17(17):2471-7
[2] FDA Sculptra Prescribing Information, June 2004, p. 1. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
HIV/AIDS-Related Uses
PLLA was approved by the FDA on August 3, 2004, for the restoration and correction of the signs of facial fat loss in people with HIV. [1] Facial wasting is a common and disfiguring side effect of highly active antiretroviral therapy (HAART). Both nucleoside analogues and protease inhibitors are associated with the development of lipoatrophy. [2]
PLLA was approved in 1999 in Europe under the brand name New-Fill for the cosmetic treatment of wrinkles and has been used by an estimated 100,000 people. Dermik Laboratories, a Pennsylvania-based division of Sanofi-Aventis, filed with the FDA for premarket approval of PLLA in the United States under the brand name Sculptra. [3] On March 25, 2004, the FDA's General and Plastic Surgery Devices Advisory Panel recommended conditional approval for Sculptra for the treatment of HIV-associated lipoatrophy. Requirements for approval in the United States included a physician training program, a postmarket study enrolling women and people of color, clear labeling with warnings against off-label use, and a description of the product as having a reconstructive rather than a cosmetic purpose. Such strong labeling conditions are intended to greatly reduce the likelihood of adverse events reported in three previous U.S. trials and to discourage off-label use in HIV uninfected people. [4]
References
[1] Dermik Laboratories Press and Media: FDA Approves Sculptra [press release], August 3, 2004. Available at: http://www.dermik.com/press/2004/08/0301.aspx. Accessed 01/23/07.
[2] AIDS 2003 Nov 21;17(17):2471-7
[3] FDA Brief Summary From the General and Plastic Surgery Devices Panel Meeting. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/G
eneralandPlasticSurgeryDevicesPanel/ucm124743.htm. Accessed 01/23/07.
[4] Clinical Care Options for HIV New-Fill Recommended for Approval in U.S. as Sculptra [news report], April 2, 2004. Available at: http://clinicaloptions.com/hiv/news/news_NAM_259.asp. Accessed 01/23/07.
Dosing Information
Mode of Delivery
Deep dermis or subcutaneous (SQ) injection. [1]
Dosage Form
Clear glass vials containing freeze-dried preparation for injection sealed with a penetrable stopper and covered by an aluminum seal with a flip-off cap. [2] Sterile lyophilisate must be reconstituted with three ml of sterile water and should be injected using a 26-gauge needle. [3]
In clinical studies, patients have received three to five injection sessions at 2-week intervals. The dosage (quantitiy of injections and of sessions) depends upon the severity of facial depression. [4]
Storage
Store PLLA injection at room temperature, up to 30 C (86 F). Do not freeze. [5]
References
[1] Sanofi-Aventis Sculptra Prescribing Information, June 2006. Available at: http://products.sanofi-aventis.us/sculptra/sculptra.html. Accessed 01/23/07.
[2] FDA Sculptra Prescribing Information, June 2004, p. 7. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
[3] FDA General and Plastic Surgery Devices Panel Meeting, 03/25/04. Available at: http://www.fda.gov/ohrms/dockets/ac/04/transcripts/4031t1.htm. Accessed 01/23/07.
[4] Sanofi-Aventis Sculptra Prescribing Information, June 2006. Available at: http://products.sanofi-aventis.us/sculptra/sculptra.html. Accessed 01/23/07.
[5] FDA Sculptra Prescribing Information, June 2004, p. 11. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
Pharmacology
PLLA is the only treatment approved to correct sunken cheeks, hollow eyes, indentations, and other signs of facial fat loss, a common side effect of antiretroviral therapy for HIV. PLLA is injected into and around the deep dermis. The injections provide a gradual and significant increase in skin thickness, improving the appearance of folds and sunken areas. [1]
In a study of fifty HIV infected patients with severe facial atrophy, mean increases in facial total cutaneous thickness (TCT) of 6.8 mm were reported at Week 96, and 43% of patients had a facial TCT greater than 10 mm at Week 96. Patients in the study received three, four, or five sets of PLLA injections at 2-week intervals. One vial of reconstituted PLLA was injected into multiple points of each cheek per session. The number of sessions and the quantity of injected PLLA were dependent upon the severity of facial depression. [2]
A single-center study of PLLA was conducted in thirty HIV infected patients with facial lipoatrophy, and patients were followed for 12 or 24 weeks. All patients received three injection sessions conducted at 2-week intervals. All patients experienced statistically-significant increases in mean skin thickness compared with baseline. A mean increase in skin thickness of approximately 4 to 6 mm was observed in all patients at Week 12. In the fourteen patients observed for 24 weeks, mean increase in skin thickness was approximately 5 mm at Week 24. [3]
The progressive increase in dermal thickness may result from a local reaction followed by a progressive increase in collagen deposition. The bioactive material is degraded and safely undergoes resorption. Although PLLA injections are associated with an increase in TCT, there is no increase in subcutaneous fat. [4] For most people who participated in PLLA clinical studies, the treatment results lasted for up to 2 years after the first treatment session. [5]
References
[1] Dermik Laboratories Press and Media: FDA Approves Sculptra [press release], August 3, 2004. Available at: http://www.dermik.com/press/2004/08/0301.aspx. Accessed 01/23/07.
[2] Sanofi-Aventis Sculptra Prescribing Information, June 2006. Available at: http://products.sanofi-aventis.us/sculptra/sculptra.html. Accessed 01/23/07.
[3] Sanofi-Aventis Sculptra Prescribing Information, June 2006. Available at: http://products.sanofi-aventis.us/sculptra/sculptra.html. Accessed 01/23/07.
[4] AIDS 2003 Nov 21;17(17):2471-7
[5] Dermik Laboratories Press and Media: FDA Approves Sculptra [press release], August 3, 2004. Available at: http://www.dermik.com/press/2004/08/0301.aspx. Accessed 01/23/07.
Adverse Events/Toxicity
PLLA injection has been associated with some adverse effects. In five clinical studies of HIV infected patients, no major adverse events were reported. Mild to moderate adverse events included bruising and hematoma related to injection. [1] The most common device-related adverse event was delayed occurrence of subcutaneous papules, which were confined to the injection site and were typically palpable, asymptomatic, and nonvisible. [2] Side effects reported at the March 25, 2004, meeting of the FDA General and Plastic Surgery Devices Advisory Panel included discomfort, bruising, edema, hematoma, inflammation, and erythema at the injection site. [3]
All patients had some degree of postinjection edema. A large proportion of patients (77%) experienced pain during the injection procedure, and about 28% of these patients required pain medication. About 13% of patients had postinjection noninflammatory nodules or papules. Severe side effects observed in limited clinical trials of PLLA included vagal hypertonia and lightheadedness (7.5%), inflammatory nodule development (1%), facial palsy upon hitting the facial nerve during treatment (1%), and anaphylaxis (1%). [4]
References
[1] FDA Brief Summary from the General and Plastic Surgery Devices Panel Meeting. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/G
eneralandPlasticSurgeryDevicesPanel/ucm124743.htm. Accessed 01/23/07.
[2] Sanofi-Aventis Sculptra Prescribing Information, June 2006. Available at: http://products.sanofi-aventis.us/sculptra/sculptra.html. Accessed 01/23/07.
[3] FDA Sculptra Prescribing Information, June 2004, pp. 3-4. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
[4] Natap.org HIV Articles: Report 2 on Sculptra (New-Fill): FDA Study Review; Advocacy Issues. Available at: http://www.natap.org/2004/HIV/032904_02.htm. Accessed 01/23/07.
Drug and Food Interactions
No studies of interactions with PLLA with drugs or other substances or implants have been done. [1]
References
[1] FDA Sculptra Prescribing Information, June 2004, p. 2. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
Contraindications
PLLA should not be used in any person who has hypersensitivity to any of the components of the product. [1]
References
[1] FDA Sculptra Prescribing Information, June 2004, p. 1. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Poly-L-lactic acid.
Chemistry
CAS Name
Propanoic acid, 2-hydroxy-, (S)-, homopolymer [1]
CAS Number
26811-96-1 [2]
Molecular Formula
(C3-H6-O3)x-
Molecular Weight
40 to 50 kDa
Stability
Each vial of PLLA for injection is packaged for single-use only; do not resterilize. [3]
PLLA is physically, chemically, and microbiologically stable for up to 72 hours after reconstitution, and for up to 2 years as a lyophilisate. [4] [5]
References
[1] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 01/23/07.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 01/23/07.
[3] FDA Sculptra Prescribing Information, June 2004, p. 11. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm. Accessed 01/23/07.
[4] Natap.org HIV Articles: Report 2 on Sculptra (New-Fill): FDA Study Review; Advocacy Issues. Available at: http://www.natap.org/2004/HIV/032904_02.htm. Accessed 01/23/07.
[5] FDA General and Plastic Surgery Devices Panel Meeting, 3/25/04. Available at: http://www.fda.gov/ohrms/dockets/ac/04/transcripts/4031t1.htm. Accessed 01/23/07.
Further Reading
Sculptra Prescribing Information from the FDA web site [PDF]. A more current version may be available on the manufacturer's web site.
Barton SE, Engelhard P, Conant M. Poly-L-lactic acid for treating HIV-associated facial lipoatrophy: a review of the clinical studies. Int J STD AIDS. 2006 Jul;17(7):429-35.
Cattelan AM, Bauer U, Trevenzoli M, Sasset L, Campostrini S, Facchin C, Pagiaro E, Gerzeli S, Cadrobbi P, Chiarelli A. Use of polylactic acid implants to correct facial lipoatrophy in human immunodeficiency virus 1-positive individuals receiving combination antiretroviral therapy. Arch Dermatol. 2006 Mar;142(3):329-34.
El-Beyrouty C, Huang V, Darnold CJ, Clay PG. Poly-L-lactic acid for facial lipoatrophy in HIV. Ann Pharmacother. 2006 Sep;40(9):1602-6. Epub 2006 Aug 15. Review.
Mest DR, Humble G. Safety and efficacy of poly-L-lactic acid injections in persons with HIV-associated lipoatrophy: the US experience. Dermatol Surg. 2006 Nov;32(11):1336-45.
Moyle GJ, Brown S, Lysakova L, Barton SE. Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy. HIV Med. 2006 Apr;7(3):181-5.
Manufacturer Information
Poly-L-lactic acid
Dermik Laboratories, Inc.
1050 Westlakes Dr.
Berwyn, PA 19312
Phone: 484-595-2700
Fax: 484-595-2733
Sculptra
Dermik Laboratories, Inc.
1050 Westlakes Dr.
Berwyn, PA 19312
Phone: 484-595-2700
Fax: 484-595-2733
Last Updated: January 23, 2007