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Today, August 1, 2017, FDA approved revisions to the Epclusa (sofosbuvir/velpatasvir) label to include information from adult patients co-infected with chronic hepatitis C virus infection and HIV-1 infection based upon the data from the ASTRAL-5 clinical trial. The major changes include the following: Section 2: DOSAGE AND ADMINISTRATION: 2.2 Recommended Dosage The recommended dosage of EPCLUSA is one tablet taken orally once daily with or without food [see Clinical Pharmacology (12.3)]. One tablet of EPCLUSA contains 400 mg of sofosbuvir and 100 mg of velpatasvir. Table 1 shows the recommended treatment regimen and duration based on patient population. For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in Table 1 [see Clinical Studies (14.3)]. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs. Table 1 Recommended Treatment Regimen in Patients with Genotype 1, 2, 3, 4, 5, or 6 HCV
a In clinical trials, regimens contained peginterferon alfa/ribavirin with or without an HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir). b When administered with EPCLUSA, the recommended dosage of ribavirin is based on weight (administered with food): 1000 mg per day for patients less than 75 kg and 1200 mg for those weighing at least 75 kg, divided and administered twice daily. The starting dosage and on-treatment dosage of ribavirin can be decreased based on hemoglobin and creatinine clearance. For ribavirin dosage modifications, refer to the ribavirin prescribing information. Section 6: ADVERSE REACTIONS updated to include the safety findings from ASTRAL-5 along with post-marketing experience Adverse Reactions in Subjects Coinfected with HCV and HIV-1 The safety assessment of EPCLUSA in subjects with HCV/HIV-1 co-infection was based on an open-label clinical trial (ASTRAL-5) in 106 subjects who were on stable antiretroviral therapy [see Clinical Studies (14.3)]. The safety profile in HCV/HIV-1 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of sofosbuvir. Because post-marketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Tissue Disorders updated to include: Skin rashes, sometimes with blisters or angioedema-like swelling Section 14: CLINICAL STUDIES updated to include the efficacy results from ASTRAL-5 as follows 14.3 Clinical Trial in Subjects Coinfected with HCV and HIV-1 ASTRAL-5 was an open-label trial that evaluated 12 weeks of treatment with EPCLUSA in subjects with genotype 1, 2, 3, 4, 5 or 6 HCV infection who were co-infected with HIV-1. Subjects were on a stable HIV-1 antiretroviral therapy that included emtricitabine/tenofovir disoproxil fumarate or abacavir/lamivudine administered with atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, raltegravir or elvitegravir/cobicistat. Of the 106 treated subjects, the median age was 57 years (range: 25 to 72); 86% of the subjects were male; 51% were White; 45% were Black; 22% had a baseline body mass index at least 30 kg/m2; the proportions of patients with genotype 1, 2, 3, or 4 HCV infection were 74%; 10%; 11%, and 5% respectively; no subjects with genotype 5 or 6 HCV were treated with EPCLUSA; 77% had non- CC IL28B alleles (CT or TT); 74% had baseline HCV RNA levels of at least 800,000 IU/mL; 18% had compensated cirrhosis; and 29% were treatment experienced. The overall mean CD4+ count was 598 cells/µL (range: 183−1513 cells/µL) and 57% of subjects had CD4+ counts > 500 cells/μL. Table 14 presents the SVR12 for the ASTRAL-5 trial by HCV genotype.
a The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment. No subject had HIV-1 rebound during treatment and CD4+ counts were stable during treatment. The updated labels will soon be available drugs@fda or DailyMed Steve Morin Richard Klein Kimberly Struble For more information about the HIV Liaison Program visit the FDA Patient Network Subscriber Services:
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