Food and Drug Administration - August 14, 2007
Richard Klein & Kimberly Struble

FDA, on August 13, 2007, granted tentative approval for a new fixed dose three-drug combination pill containing generic lamivudine, stavudine and nevirapine, to treat human immunodeficiency virus (HIV-1) infection in children outside the United States. This is the first combination of its kind available to meet the needs of children less than 12 years of age, and represents a major advance in global AIDS treatment efforts. The generic combination drug tablet is manufactured by Cipla Limited, of Mumbai, India.

The new combination constitutes a complete HIV regimen that is taken twice daily, once patients have tolerated 14 days of lead-in treatment with nevirapine taken once daily in combination with separate doses of lamivudine and stavudine. The combination tablet can be dissolved in water for children who cannot swallow tablets.

Each ingredient of this generic tablet is currently approved to treat HIV-1 in combination with other antiretroviral agents. The safety and effectiveness of the combination of lamivudine-stavudine-nevirapine in lowering viral load and increasing CD4+ cells has been demonstrated in previously conducted controlled studies of the individual ingredients used together.

The three drugs, combined in a single twice-a-day tablet is not only easier to administer to children, increasing access and adherence to therapy, but also facilitates storage and distribution. This new combination represents a significant advance in the treatment of children infected with HIV in PEPFAR countries.

Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards. But because of existing patents and/or exclusivity rights, it may not be marketed in the U.S. The tentative approval, does however, make the product eligible for consideration for purchase under the PEPFAR program.

As with all generic applications, FDA conducts on-site inspections of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application, ensuring that antiretroviral drugs purchased by PEPFAR meet the same safety, efficacy, and manufacturing standards as drugs used in the United States.

This product was reviewed under guidance titled Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously approved Antiretrovirals for the Treatment of HIV developed by FDA to clarify what regulatory requirements apply to such applications, what issues might be of concern, how these issues should be addressed, and to encourage sponsors to submit applications for combination and co-packaged products to FDA.

The tentative approvals of nevirapine (notice sent yesterday) and this triple fixed dose combination tablet of lamivudine, stavudine and nevirapine represent the 50th and 51st approvals or tentative approvals, respectively, by FDA under the expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR). A list of all approvals and tentative approvals under these provisions can be found at http://www.fda.gov/oia/pepfar.htm

Richard Klein | Office of Special Health Issues | Food and Drug Administration

Kimberly Struble | Division of Antiviral Drug Products | Food and Drug Administration

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SOURCE: Food and Drug Administration (FDA).

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