Sofosbuvir (Sovaldi) Dosing and Drug Interactions – December 2013 John J Faragon, PharmD, BCPS, AAHIV-­‐P Description – HCV NS5b polymerase inhibitor indicated for the treatment of chronic hepatitis C virus infection as a component of combination antiviral treatment regimen. Sofosbuvir efficacy established for HCV genotype 1, 2, 3 or 4 infection, including patients with HCV and HIV co-­‐infection and those with hepatocellular carcinoma. Dose and Duration – 400mg orally once daily with or without food in combination with either ribavirin alone or with peginterferon alpha + ribavirin depending on HCV genotype. Do not use sofosbuvir as monotherapy. Geotype 1 or 4 – Sofosbuvir + peginterferon alfa + weight based ribavirin for 12 weeks. In patients with HCV genotype 1 ineligible for peginterferon alfa, 24 weeks of sofosbuvir + ribavirin alone may be considered. Genotype 2 – Sofosbuvir + weight based ribavirin for 12 weeks Genotype 3 – Sofosbuvir + weight based ribavirin for 24 weeks For patients with hepatocellular carcinoma awaiting liver transplantation, sofosbuvir in combination with ribavirin for up to 48 weeks or until liver transplantation, can be used to prevent post-­‐transplant HCV reinfection. How Supplied – 400mg tablet Dose Adjustments – No dosage recommendation can be provided for patients with severe renal disease or end stage renal disease, as sofosbuvir metabolites can be increased up to 20-­‐fold in this setting. No dose adjustment of sofosbuvir required for patients with mild, moderate or severe hepatic impairment (Child-­‐Pugh Class A, B or C). Safety Information –The most common adverse events for sofosbuvir + ribavirin were fatigue and headache. The most common adverse events for sofosbuvir when combined with peginterferon alfa + ribavirin were fatigue, headache, nausea, insomnia and anemia. PK/Drug Interactions – Potent intestinal P-­‐glycoprotein inducers are likely to reduce sofosbuvir levels. Studies with HIV medications that have NOT been shown to interact include darunavir/ritonavir, efavirenz, emtricitabine, raltegravir, rilpivirine, or tenofovir disoproxil fumarate. Specific Drug Interactions Concomitant Drug Class: Drug Name Anticonvulsants: carbamazepine, phenytoin, phenobarbital, oxcarbazepine Antimycobacterials: rifabutin, rifampin, rifapentine Herbal Supplements: St. John’s wort (Hypericum perforatum) HIV Protease Inhibitors: tipranavir/ritonavir Clinical Comment Use of sofosbuvir with carbamazepine, phenytoin, phenobarbital or oxcarbazepine is expected to decrease the concentration of sofosbuvir. Coadministration not recommended. Use of sofosbuvir with rifampin, rifabutin or rifapentine is expected to decrease the concentration of sofosbuvir. Coadministration not recommended. Use of sofosbuvir with St. John’s wort is expected to decrease the concentration of sofosbuvir. Co-­‐administration not recommended. Use of sofosbuvir with tipranavir/ritonavir is expected to decrease the concentration of sofosbuvir. Coadministration not recommended. Patient Counseling Tips: Take whole tablet with or without food, do not crush. Screen for potential drug interactions, including herbal therapy, prior to initiating sofosbuvir. www.nynjaetc.org