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FDA Approves Elvitegravir and Cobicistat Booster as Stand-alone Drugs

The U.S. Food and Drug Administration (FDA) this week approved Gilead Sciences next-generation HIV integrase inhibitor elvitegravir (brand name Vitekta) and pharmacoenhancer cobicistat (Tybost) as stand-alone agents to be used in combination antiretroviral therapy. The 2 drugs were already available as part of the Stribild single-tablet regimen.

Elvitegravir

The FDA-approved indication for elvitegravir is for use with a ritonavir-boosted protease inhibitor plus at least 1 other antiretroviral for treatment-experienced patients. In a Phase 3 trial of treatment-experienced adults with drug-resistant HIV, elvitegravir worked as well as the approved integrase inhibitor raltegravir (Isentress) when combined with a fully active ritonavir-boosted protease inhibitor and other antiretroviral drug(s).

Like raltegravir and the other approved integrase inhibitor, dolutegravir (Tivicay, also in the recently approved Triumeq single-tablet regimen), elvitegravir is generally well-tolerated and side effects are uncommon. The most frequently reported adverse events in clinical trials were diarrhea, nausea, and headache.

Elvitegravir will be sold as 85 mg and 150 mg tablets and should be administered once-daily with food. It is not yet approved for use with cobicistat outside the Stribild regimen, and the FDA states that "[elvitegravir] coadministered with protease inhibitors and cobicistat is not recommended."

Administering elvitegravir with other drugs that act as CYP3A inducers could reduce elvitegravir to sub-therapeutic levels. It should not be administered with numerous drugs for various conditions, should be taken 2 hours apart from antacids, and women should use non-hormonal contraception.

Cobicistat

Cobicistat increases blood levels of elvitegravir and certain other antiretrovirals by interfering with the drug-processing CYP3A enzyme in the liver, but it is not itself active against HIV. Studies have found that cobicistat worked as well as ritonavir as a booster for atazanavir (Reyataz) or darunavir (Prezista).

The FDA approved cobicistat specifically as a booster for 300 mg atazanavir or 800 mg darunavir when taken once-daily with food. It is approved for both treatment-naive and treatment-experienced patients.

The FDA cautions that cobicistat "is not interchangeable with ritonavir" to boost 600 mg twice-daily darunavir or other HIV protease inhibitors, and its interactions with other drugs are unpredictable. As noted above, cobicistat is not yet approved as a booster for elvitegravir outside the Stribild regimen. It should not be used in addition to ritonavir

Ritonavir -- the only other approved pharmacoenhancer -- is itself active against HIV and was initially used as a stand-alone protease inhibitor, but its use is limited by toxicity and unwanted drug interactions at higher doses. Cobicistat is generally safe and well-tolerated. It increases blood levels of serum creatinine, a kidney biomarker, but does not affect actual glomerular filtration. The most common adverse effects of cobicistat in combination with atazanavir are jaundice and yellowing of the eyes.

Complete labeling information for Vitekta and Tybost will be posted soon at Drugs@FDA.

9/26/14

Sources

R Klein, K Struble, and S Morin, U.S. Food and Drug Administration. HIV/AIDS Update -- Approval of Vitekta. September 25, 2014.

R Klein, K Struble, and S Morin, U.S. Food and Drug Administration. HIV/AIDS Update -- Approval of Tybost (cobicistat) 150 mg tablets. September 25, 2014.