Company: Gilead Sciences
Pharmacologic class: Hepatitis C virus (HCV) NS5B polymerase inhibitor.
Active ingredient: Sofosbuvir 400mg; tabs.
Indication: As a component of a combination antiviral treatment regimen for chronic hepatitis C (CHC) genotype 1, 2, 3, or 4 infection, including persons with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplant), and those with HCV/HIV-1 co-infection. Not for use as monotherapy.
Pharmacology: Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. This nucleotide prodrug undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator.
Clinical trials: The safety and efficacy of Sovaldi was evaluated in five phase 3 trials in a total of 1,724 HCV mono-infected subjects with genotypes 1-6 CHC and one phase 3 trial in 223 HCV/HIV-1 co-infected subjects with genotype 1, 2, or 3 CHC. The primary endpoint was sustained virologic response (SVR), which was defined as HCV RNA less than lower limit of quantification at 12 weeks after the end of treatment.
NEUTRINO was an open-label, single-arm trial that evaluated 12 weeks of treatment with Sovaldi in combination with peginterferon (PegIFN) alfa 2a (Pegasys) and ribavirin (RBV) (Copegus, Rebetol, Ribasphere, Virazole) in treatment-naïve subjects with genotype 1, 4, 5, or 6 HCV infection compared with prespecified historical control SVR rate of 60% (P <0.001). The overall SVR rate was 90% (295/327). The SVR rates by specific genotype were: genotype 1, 89% and genotype 4, 96%.
FISSION was an active-controlled trial that evaluated 12 weeks of treatment with Sovaldi plus RBV vs. 24 weeks with PegIFN plus RBV in treatment-naïve subjects with genotype 2 and 3 HCV. The overall SVR rate for both arms was 67%. The SVR rates for genotype 2 was 95% vs. 78% and genotype 3 was 56% vs. 63% in the Sovaldi-plus-RBV arm compared with the PegIFN-plus-RBV arm, respectively.
Adults: 400 mg once daily. Genotype 1: Treat for 12 weeks (with PegIFN alfa plus RBV) or 24 weeks (with RBV) if interferon- based regimen ineligible. Genotype 2: Treat for 12 weeks (with RBV). Genotype 3: Treat for 24 weeks (with RBV).Genotype 4: Treat for 12 weeks (with PegIFN alfa plus RBV). Hepatocellular carcinoma: Treat up to 48 weeks (with RBV) or until time of liver transplant, whichever occurs first. Dose reduction of sofosbuvir is not recommended. Other dose modifications: See full labeling. If PegIFN alfa or RBV are discontinued, sofosbuvir should also be discontinued.
Children: <18 years: not established.
Contraindications: Pregnant women and in men whose partners are pregnant. (Note: RBV is Cat. X.) PegIFN and RBV contraindications also apply to combination therapy with sofosbuvir.
Warnings/Precautions: Female patients/partners of male patients must have negative pregnancy test before initiating therapy; use two effective nonhormonal methods of contraception during and for six months after treatment completion; perform routine monthly pregnancy test. Severe renal impairment or end-stage renal disease. Decompensated cirrhosis. Post-liver transplant recipients. Pregnancy (Cat. B). Nursing mothers: not recommended.
Interactions: Avoid concomitant strong P-gp inducers (e.g., rifampin [Rifadin], St. John’s wort). Antagonized by carbamazepine, phenytoin (Dilantin, Phenytek), phenobarbital, oxcarbazepine (Trileptal), rifabutin (Mycobutin), rifapentine (Priftin), tipranavir/ritonavir (Aptivus/Norvir); avoid concomitant use. May be coadministered with P-gp and/or breast cancer resistance protein inhibitors. (See full labeling.)
Adverse reactions: Rash fatigue, headache, nausea, insomnia, anemia, pruritus.
How supplied: Tabs—28
For more information, call 800.445.3235 or visit www.Sovaldi.com.