Sofosbuvir

What it is and how it works

Sofosbuvir is a nucleotide analogue prodrug metabolised in hepatocytes to an active uridine triphosphate analogue, which is incorporated into hepatitis C virus RNA by the NS5B RNA-dependent RNA polymerase and acts as a chain terminator. It is active against all HCV genotypes and has a high barrier to resistance.

Indications

Chronic hepatitis C infection in adults (and children according to licence), always in combination with other antivirals such as an NS5A inhibitor (e.g. daclatasvir, velpatasvir, ledipasvir) or ribavirin.

Dosage and administration (summary)

Taken orally, 400 mg once daily with or without food, for 12 or 24 weeks depending on genotype, liver disease status and combination regimen.

Contraindications

Hypersensitivity to sofosbuvir; concomitant use with strong P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, St John’s wort); with ribavirin-containing regimens, the contraindications of ribavirin also apply.

Warnings and precautions

Severe bradycardia and heart block have occurred when given with amiodarone, so this combination should be avoided or closely monitored. Screen for hepatitis B before treatment because of the risk of HBV reactivation, and monitor glucose in diabetics as glycaemic control may improve.

Pregnancy

Limited data in pregnancy; avoid when combined with ribavirin, which is teratogenic.

Storage and supply

Store below 30 °C.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.