Approval of Atripla
July 12, 2006
The Food and Drug Administration (FDA) today (July 12, 2006) approved Atripla Tablets, a new fixed-dose combination of three widely used antiretroviral drugs, to be taken in a single tablet once a day, alone or in combination with other antiretroviral products for the treatment of HIV-1 infection in adults. Atripla is the first fixed dose combination available in the United States to combine two different classes of antiviral drugs in a single pill. This "one-pill-once-a-day" product to treat HIV/AIDS combines the active ingredients of Sustiva (efavirenz) a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), with Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate), two Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Emtriva and Viread are also available in a fixed dose combination known as Truvada.
Atripla is the result of an unprecedented inter-company cooperative effort between Gilead Sciences, the manufacturer of Emtriva and Viread, with Bristol-Myers Squibb, the manufacturer of Sustiva. Merck controls the marketing of Sustiva outside the United States. The approval of Atripla will not only make the new fixed dose combination available in the U.S., but also permit its purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Atripla was approved in less than 3 months under FDA's fast track program. The approval is the result of an expedited review process outlined in guidance for industry from the FDA in May 2004. The guidance encourages manufacturers to develop fixed dose combination and co-packaged products consisting of previously approved antiretroviral therapies for the treatment of HIV infection.
The drug combination represented by this product is a recommended first line regimen for treatment naive patients (except during first trimester of pregnancy or in women with high pregnancy potential) in the national Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.
Atripla can significantly simplify a drug treatment regimen by reducing the pill burden, helping to increase adherence and thus reducing potential development of viral resistance to the drugs. This may result in longer term effectiveness of the drug regimen.
Since the three components of Atripla have been in use for some time, their characteristics and effects are well known. In addition, the safety and effectiveness of the combination of these three drugs were shown in a 48 week-long clinical study with 244 HIV-1 infected adults receiving the drugs contained in Atripla. In this trial, 80 percent of the participants achieved a marked reduction of the human immunodeficiency virus and a substantial increase in the number of healthy CD4 cells.
The labeling of Atripla includes a boxed warning that the drug's use can cause lactic acidosis (buildup of an acid in the blood). In patients with chronic Hepatitis B infection, the discontinuation of the treatment with Atripla (which is not indicated for this use) can result in severe flare-ups of Hepatitis B infection. Other potential serious adverse events reported for the use of Atripla's ingredients include serious liver toxicity, renal impairment and severe depression. The most common adverse events experienced by participants in the combination trial included headache, dizziness, abdominal pain, nausea, vomiting, and rash.
FDA approved Sustiva in 1998, Viread in 2001 and Emtriva in 2003. Truvada, which combined Viread and Emtriva in a fixed dose combination, was approved in 2004.
A PDF copy of the labeling is available here.
This article was provided by U.S. Food and Drug Administration. Visit the FDA's website to find out more about their activities and publications.