The FDA has approved Mavyret (Abbvie) and Vosevi (Gilead), two new fixed-dose combinations of direct-acting antiviral (DAA) drugs, for treatment of chronic hepatitis C virus (HCV) infection caused by any of the six major HCV genotypes in patients without cirrhosis or with compensated cirrhosis. Both are approved for use in treatment-experienced patients. Mavyret is also approved for treatment-naive patients.

The FDA has approved a fixed-dose combination (Harvoni [har voe' nee] – Gilead) of sofosbuvir and ledipasvir (led' i pas' vir), two oral direct-acting antiviral agents, for treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Genotype 1 is responsible for 70-80% of HCV infections in the US. Sofosbuvir (Sovaldi) was approved earlier for use in combination with other antiviral drugs for treatment of HCV infection. Ledipasvir is a new drug.

The FDA has recently approved 2 new drugs for treatment of chronic hepatitis C virus (HCV) infection. Simeprevir (Olysio – Janssen) is the third oral protease inhibitor to be approved for use in combination with peginterferon and ribavirin for treatment of chronic HCV genotype 1 infection in adults with compensated liver disease. Telaprevir (Incivek) and boceprevir (Victrelis) were approved in 2011 for the same indication. Sofosbuvir (Sovaldi – Gilead), a nucleotide analog polymerase inhibitor that has been approved for use with and without interferon for treatment of multiple HCV...

View Table: Mechanisms of Drug Interactions

The FDA has approved the nucleotide polymerase inhibitor sofosbuvir (Sovaldi – Gilead) for use in combination with other antiviral drugs for treatment of chronic hepatitis C virus (HCV) infection.

The FDA has approved Biktarvy (Gilead), a once-daily, fixed-dose combination of bictegravir, a new integrase strand transfer inhibitor (INSTI), and the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir alafenamide (TAF), for treatment of HIV-1 infection in adults. The new combination is indicated for use in patients who are antiretroviral-naive or who have been virologically suppressed on a stable antiretroviral regimen for ≥3 months with no history of treatment failure and no known substitutions associated with resistance to any component of the...

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Harvoni, a once-daily fixed-dose combination of the direct-acting antiviral agents ledipasvir and sofosbuvir approved by the FDA in 2014 for treatment of hepatitis C virus (HCV) genotype 1 infection,1 has now been approved for use in patients infected with HCV genotype 4, 5, or 6, and in patients co-infected with HCV and HIV-1. A 12-week course of treatment with Harvoni plus ribavirin has also been approved as an alternative to 24 weeks of Harvoni alone for treatment-experienced, cirrhotic patients with HCV genotype 1 infection.HCV genotypes 4, 5, and 6 are responsible for <2% of HCV cases...

The FDA has approved Triumeq (Viiv Healthcare), a fixed-dose combination of the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine, for once-daily treatment of HIV-1 infection. Dolutegravir (Tivicay) was approved as a single agent in 2013.

Cobicistat, a pharmacokinetic enhancer that boosts levels of some HIV drugs but has no antiretroviral activity of its own, is now available alone as Tybost (Gilead) and in fixed-dose combinations with the protease inhibitors atazanavir (Evotaz — BMS) and darunavir (Prezcobix — Janssen) for treatment of HIV-1 infection. Both atazanavir and darunavir have traditionally been used in combination with the CYP3A inhibitor ritonavir (Norvir) to boost their serum concentrations, but neither is available in a fixed-dose combination with ritonavir.