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 
http://www.fda.gov/cder/guidance/6360fnl.pdf 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 
http://www.pepfar.gov). 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