FDA approves fixed-dose combination of efavirenz/tenofovir/FTC (Atripla): joint company collaboration produces once-daily one pill combination

On 12 July 2006, the Food and Drug Administration (FDA) today approved Atripla, 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 ARVs.

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 efavirenz (an NNRTI), with FTC (emtricitabine) and tenofovir DF (NRTIs). FTC and tenofovir are also available in a fixed dose combination (Truvada).

Atripla is the result of an inter-company cooperative effort between Gilead Sciences, the manufacturer of FTC and tenofovir, with Bristol-Myers Squibb, the manufacturer of efavirenz. Merck controls the marketing of Sustiva outside the United States.

Atripla was approved in less than 3 months under FDA’s fast track program. Achieving a bioequivilant formulation was a significant challenge, and at least four earlier formulations failed to produce bioquiviance within the required range for all three drugs. The approval is the result of an expedited review process outlined in guidance for industry from the FDA in May 2004 that encourages manufacturers to develop fixed dose combination and co-packaged products consisting of previously approved antiretroviral therapies for the treatment of HIV infection.

The labeling of Atripla includes a boxed warning that the drug’s use can cause lactic acidosis. 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 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 efavirenz (Sustiva) in 1998, tenofovir DF (Viread) in 2001 and FTC (Emtriva) in 2003. Truvada, which combined tenofovir and FTC in a fixed dose combination, was approved in 2004.

Source: FDA listserv

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