Sofosbuvir (Sovaldi ™) UTILIZATION MANAGEMENT CRITERIA DRUG CLASS: Nucleotide Analog NS5B Polymerase Inhibitor BRAND (generic) NAME: Sovaldi (sofosbuvir ) 400 mg strength tablet FDA -APPROVED INDICATIONS Sovaldi is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. • Sovaldi efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV -1 co-infection. COVERAGE AUTHORIZATION CRITE RIA Sofosbuvir (Sovaldi) is cover ed for the following condition and situations: • Diagnosis of chronic hepatitis C (CHC) infection with c onfirmed genotype 1, 2, 3, or 4, OR • CHC infection with hepatocellular carcinoma awaiting liver transplant, AND • Sofosbuvir is prescribed in combination with ribavirin and pegylated interferon alfa for genotypes 1 and 4, OR • Sofosbuvir is prescribed in combination with ribavirin for p atients with genotype 1 who are peginterferon-ineligible* (medical record documentation of ineligibility for peginterferon therapy must be submitted for review), OR • Sofosbuvir is prescribed in combination with simeprevir, with or without ribavirin, for 12 weeks duration of therapy, for patients with genotype 1 that have advanced fi brosis (METAVIR score 2, 3, 4, OR cirrhosis secondary to Hepatitis C ), and are peginterferon - ineligible* (medical record documentation of ineligibility for peginterferon therapy m ust be submitted for review). In addition, the patient may either be treatment naïve, OR patient may have tried and failed previous treatment with peginterferon and ribavirin, OR • Sofosbuvir is prescribed in combination with ribavirin for genotypes 2 and 3 and/or in CHC patients with hepatocellular carcinoma awaiting liver transplant , AND • Sofosbuvir is prescribed by or in consultation with a physician with expertise and experience in the management of infectious hepatitis, AND • Not covered in pregnant women and men whose female partners are pregnant ( for combination therapy regimens that include ribavirin). *Peginterferon-ineligible, defined as one or more of the below: • Autoimmune hepatitis • Other autoimmune disorders, such as, myositis, thrombotic thrombocytopenic purpura, 1 Last Revision Date: August 2014 idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus • Hypersensitivity to peginterferon or any of its components • Decompensated cirrhosis • History of depression, or clinical features consistent with depression or other neuropsychiatric conditions which would preclude safe use of peginterferon-based therapy • History of preexisting cardiac disease • Bone marrow suppression o Baseline neutrophil count below 1500/ µL o Baseline platelet count below 90,000/ µL o Baseline hemoglobin below 10 g/dL Duration of Approval Patients with genotype 1 or 4 CHC Sovaldi + peginteferon alfa + ribavirin 12 weeks Patients with genotype 1 who Sovaldi + simeprevir 12 weeks have advanced fibrosis (METAVIR (with or without ribavirin) score 2, 3, 4 OR cirrhosis secondary to Hepatitis C) and are peginterferon-ineligible* Patients with genotype 1 who are Sovaldi + ribavirin 24 weeks peginterferon-ineligible* Patients with genotype 2 CHC Sovaldi + ribavirin 12 weeks Patients with genotype 3 CHC Sovaldi + ribavirin 24 weeks CHC patients with hepatocellular Sovaldi + ribavirin 48 weeks carcinoma awaiting liver transplant DOSAGE AND ADMINISTRATION The recommended dose of Sovaldi is one 400 mg tablet, taken orally, once daily with or without food. Sovaldi should be used in combination with ribavirin or in combination with pegylated interferon alfa and ribavirin for the treatment of CHC in adults. The recommended regimen and treatment duration for Sovaldi combination therapy is provided in Table 1. Table 1: Recommended Regimens and Treatment Duration for Sovaldi Combination Therapy in HCV Mono-infected and HCV/HIV-1 Co-Infected Patients Patients with genotype 1 or 4 Sovaldi + peginterferon alfa + 12 weeks CHC ribavirin Patients with genotype 2 Sovaldi + ribavirin 12 weeks CHC Patients with genotype 3 Sovaldi + ribavirin 24 weeks CHC Per Sovaldi package labeling; r efer to peginterferon alfa and ribavirin prescribing information for dosing. 2 Last Revision Date: August 2014 Sovaldi in combination with ribavirin for 24 weeks can be considered as a therapeutic option for CHC patients with genotype 1 infection who are ineligible to receive a peginterferon-based regimen. Treatment decision should be guided by an assessment of the potential benefits and risks for the individual patient. Sovaldi in combination with ribavirin is recommended for up to 48 weeks or until the time of liver transplantation, whichever occurs first, to prevent post-transplant HCV reinfection. CONTRAINDICATIONS Sovaldi combination treatment with ribavirin or peginterferon alfa/ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risks for birth defects and fetal death associated with ribavirin. DRUG-DRUG INTERACTIONS Drugs that are potent P-gp inducers in the intestine (e.g., rifampin, St. John’s wort) may significantly decrease sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect of Sovaldi. Rifampin and St. John’s wort should not be used with Sovaldi. Table 2: Potentially Significant Drug Interactions Drug Class Drugs Within Class Clinical Comments Anticonvulsants Carbamazepine, oxcarbazepine, Decrease concentration of sofosbuvir leading to phenobarbital, phenytoin reduced therapeutic effect; coadministration is not recommended. Antimycobacterials Rifampin, rifabutin, rifapentine Decrease concentration of sofosbuvir with rifabutin or rifapentine, leading to reduced therapeutic effect; coadministration is not recommended. Sofosbuvir should not be used with rifampin, a potent intestinal P-gp inducer. Herbal St. John’s wort Sofosbuvir should not be used with St. John’s wort, a Supplements potent intestinal P-gp inducer. HIV protease Tipranavir/ritonavir Decrease concentration of sofosbuvir leading to inhibitors reduced therapeutic effect; coadministration is not recommended. REFERENCES Sovaldi (sofosbuvir) product labeling. Gilead Sciences, Inc. Foster City, CA. December 2013. Pegasys (peginterferon alfa-2a) product labeling. Genentech USA, Inc., A Member of the Roche Group, South San Francisco, CA. February 2013. Recommendations for Testing, Managing, and Treating Hepatitis C: Initial treatment of HCV infection in patients starting treatment. http://www.hcvguidelines.org/full-report/initial-treatment- hcv-infection-patients-starting-treatment. Retrieved on 4/1/14 and 6/1/14. 3 Last Revision Date: August 2014 4 Last Revision Date: August 2014 .