Sofosbuvir
Sofosbuvir is a direct-acting antiviral (DAA) against the hepatitis C virus, formulated in fixed-dose combination tablets alongside other antivirals. The FDA label for VOSEVI describes sofosbuvir as one of the DAA agents in that fixed-dose combination, working alongside velpatasvir and voxilaprevir. Within these combinations, sofosbuvir itself acts as a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, an enzyme essential for viral replication, according to the UK product information for Ledipasvir/Sofosbuvir Gilead. Combination products built on sofosbuvir are used in adult patients with chronic hepatitis C virus infection without cirrhosis or with compensated cirrhosis, in those who have already been treated with an HCV regimen containing an NS5A inhibitor.
Hepcinat Lp
Chronic Hepatitis C Genotype 1 Infection in Adults
90mg + 400mg
Treats chronic hepatitis C virus infection by inhibiting viral replication, resulting to sustained virological response and elimination of the virus from the body.
Key points
- Sofosbuvir and its metabolite GS-331007 reach similar blood exposure whether a person is healthy or has hepatitis C infection: “Sofosbuvir and GS-331007 AUC0–24 and Cmax were similar in healthy adult subjects and subjects with HCV infection.”
- Sofosbuvir, velpatasvir and voxilaprevir are all carried by the P-gp and BCRP transport proteins; sofosbuvir’s own metabolite GS-331007 is not: “Sofosbuvir, velpatasvir, and voxilaprevir are substrates of drug transporters P-gp and BCRP while GS-331007 is not.”
- A product containing sofosbuvir should not be taken alongside another product that also contains sofosbuvir: “Ledipasvir/Sofosbuvir Gilead should not be administered concomitantly with other medicinal products containing sofosbuvir.”
How it works
Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. It is a nucleotide prodrug: inside the body it is converted to the pharmacologically active uridine analogue triphosphate GS-461203, which the NS5B polymerase can incorporate into HCV RNA, where it acts as a chain terminator.
Safety specific to sofosbuvir
Combination products containing sofosbuvir carry this boxed warning from the FDA label for VOSEVI:
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VOSEVI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAA) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated
Sofosbuvir-containing regimens also carry a risk of serious bradycardia when taken with amiodarone. Postmarketing reports describe the risk directly: “Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with a sofosbuvir-containing regimen.” A fatal case has been reported: “A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen (HARVONI® (ledipasvir/sofosbuvir)).” Onset is not always immediate: “Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment.”
For patients taking rifampin, the US label for VOSEVI states a direct contraindication: “VOSEVI is contraindicated with rifampin [see Drug Interactions (7.3), and Clinical Pharmacology (12.3)].”
When to seek urgent care
Anyone taking amiodarone together with a sofosbuvir-containing medicine should know the signs to act on. The UK product information for Ledipasvir/Sofosbuvir Gilead is direct about this: “All patients with concurrent or recent use of amiodarone should be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.”