Sofosbuvir: A Review of its Use in Patients with Chronic Hepatitis C

Abstract

Sofosbuvir (Sovaldi(®)) is a nucleotide hepatitis C virus (HCV) NS5B polymerase inhibitor that has pangenotypic antiviral activity and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of sofosbuvir in patients with chronic hepatitis C and summarizes its pharmacological properties. Interferon-free treatment with sofosbuvir plus ribavirin achieved high sustained virological response (SVR) rates in treatment-naïve and treatment-experienced patients with HCV genotype 2 or 3 infection, and also had efficacy in patients with HCV genotype 1 infection. Sofosbuvir plus ribavirin was also effective in patients co-infected with HCV and HIV, and sofosbuvir plus ribavirin administered prior to liver transplantation prevented recurrent HCV infection in the majority of patients who had HCV RNA levels below the limit of quantification at the time of transplantation. Sofosbuvir plus peginterferon-α-2a and ribavirin achieved high SVR rates in patients with HCV genotype 1 infection, and also appeared effective in patients with HCV genotype 4, 5 or 6 infection. Oral sofosbuvir was generally well tolerated in patients with chronic hepatitis C. The most commonly reported adverse events and laboratory abnormalities were consistent with those expected with ribavirin and peginterferon-α. In conclusion, sofosbuvir represents an important advance in the treatment of chronic hepatitis C.

Review article: safety and tolerability of direct‐acting anti‐viral agents in the new era of hepatitis C therapy

“…Studies investigating the pharmacokinetics of single‐ or multi‐dosing reported that no dosage modifications were required for patients with mild‐to‐moderate renal impairment. However, for patients with creatinine clearance less than 30 mL/min including those on haemodialysis, no dosage recommendation for sofosbuvir has been established . Single‐dose pharmacokinetics demonstrated the area under the curve (AUC) of the sofosbuvir metabolite GS‐331007 and, to a lesser extent, sofosbuvir itself, increased with worsening renal status.…”

Drug–drug interactions of telaprevir and boceprevir in HCV‐monoinfected and HIV/HCV‐coinfected patients can modify the adherence

“…It is important to note that the risk of the development of DDIs differs between the different new HCV direct acting antivirals. The NS5B polymerase inhibitor, sofosbuvir, is expected to cause fewer DDIs However, the second wave PI, simeprevir, is an inhibitor and substrate of CYP3A4. The NS5A inhibitor, daclatasvir, is a substrate of CYP3A4 and a substrate and inhibitor of P‐glycoprotein .…”

Hepatitis C virus: Virology, diagnosis and treatment

“…Oral sofosbuvir was generally well tolerated in CHC patients [97] ; (7) In combinations with other oral DAAs, ombitasvir (an inhibitor of the HCV NS5A) achieves very high rates of SVR (about 95%) in patients with HCV genotype 1 infection with a good tolerability [98] ; and (8) Combination of daclatasvir and asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a SVR rate of 80%-90% [99] . In October of 2014, FDA approved…”