The Food and Drug Administration (FDA) within the Department of Health and Human Services (HHS) today issued the first tentative approval for a three-ingredient fixed dose tablet for use as a stand-alone antiretroviral treatment for human immunodeficiency virus (HIV-1) infection in adults. The product (lamivudine-zidovudine-nevirapine tablet) contains the active ingredients in the widely used antiretroviral drugs Epivir (lamivudine), Retrovir (zidovudine), and Viramune (nevirapine).
The agency’s tentative approval means that although existing patents and/or exclusivity prevent approval of this product in the United States, it meets all of FDA’s manufacturing quality and clinical safety and efficacy standards required for marketing in the United States. The fixed-dose combination tablet, manufactured by Aurobindo Pharma Ltd. in Hyderabad, India, will be available for purchase and distribution in 15 other countries under the President’s Emergency Plan for AIDS Relief (PEPFAR).
“Today’s approval marks a significant step forward in our commitment to clearing the way to quickly deliver quality, life-saving HIV/AIDS drugs to people who desperately need them in developing countries. Fixed-dose combination products are an important tool in President Bush’s PEPFAR program, which seeks to combat the AIDS epidemic in the worst affected countries,” said Michael O. Leavitt, Secretary of Health and Human Service. “This new option, a fixed dose combination tablet containing lamivudine, zidovudine, and nevirapine, simplifies the treatment of HIV-1, which is a stumbling block for many individuals who find it difficult to maintain a regimen requiring the use of several drugs.”
In 2004, FDA issued a guidance encouraging manufacturers to develop fixed dose combination and co packaged products consisting of previously approved antiretroviral therapies for the treatment of HIV infection. FDA has committed to reviewing applications submitted pursuant to this guidance in an expedited manner. The guidance, which issued as part of HHS’ commitment to PEPFAR, was developed to ensure that the United States is providing safe, effective drugs to developing countries under the President’s $15 billion Emergency Plan for AIDS Relief.
“Our goal is to provide fixed dose combination products that we are confident meet all FDA standards for safety and effectiveness, as well as to ensure that we are purchasing drugs that work through the PEPFAR program,” said Dr. Scott Gottlieb, FDA Deputy Commissioner for Medical and Scientific Affairs. “Using fixed dose combinations in developing countries may provide an added advantage by improving the patient’s ability to tolerate the treatment and better adhere to treatment regimens that will help minimize the development of viral resistance and result in long-term effective control of the disease.”
The recommended regimen for the lamivudine-zidovudine-nevirapine tablet is one pill twice a day following an initial two week treatment with the individual components taken individually. Each ingredient of this generic tablet is currently approved to treat HIV-1 infected adults in combination with other antiretroviral agents. The safety and effectiveness of the combination of lamivudine-zidovudine-nevirapine in lowering the viral load and increasing the CD4+ cell has been demonstrated in previously conducted adequate and well controlled studies of the individual ingredients being used together for treatment. The labeling of the combination drug includes a Medication Guide (patient labeling) and a boxed warning that the product’s use can cause liver failure, severe rash, and lactic acidosis (buildup of an acid in the blood).
FDA may grant a tentative approval if it concludes that a drug product has met all of the required clinical safety and efficacy and manufacturing quality standards for marketing in the United States, but that full approval is not possible because of existing patents and/or exclusivity.
Within the last two years, the FDA has approved more than 20 treatments to be used as part of the PEPFAR program. PEPFAR, which President Bush first announced in his 2003 State of the Union Address, is currently providing $15 billion to fight the HIV/AIDS pandemic over five years, with a special focus on 15 of the hardest hit countries. PEPFAR is designed to prevent seven million new HIV infections, treat at least two million HIV-infected people, and care for ten million HIV-affected individuals, AIDS orphans and vulnerable children.
More information on the PEPFAR program is available online at FDA’s website: http://www.fda.gov/oia/pepfar.htm
From U.S. FDA