Vosevi is a new oral drug approved by the Food and Drug Administration to treat hepatitis C virus (HCV) infection, and the first direct-acting antiviral approved for use when other HCV treatments have failed. It is indicated for the treatment of adults with chronic HCV infection, without cirrhosis or with compensated cirrhosis, who have genotype 1, 2, 3, 4, 5, or 6 infection and who have been previously treated with an HCV regimen containing an NS5A inhibitor. It is also approved for use in those with genotype 1a or 3 infection who were previously treated with sofosbuvir without an NS5A inhibitor.
Vosevi is a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir. Of these three drugs, only voxilaprevir is a new entity. Sofosbuvir is available as monotherapy (Sovaldi) and in combination with ledipasvir (Harvoni) or velpatasvir (Epclusa). (Neither velpatasvir nor ledipasvir are marketed as single-entity drugs.) Sofosbuvir, a prodrug that becomes active after undergoing intracellular metabolism, is an HCV nucleotide analog NS5B polymerase inhibitor; it works to prevent viral replication. Velpatasvir is an HCV NS5A protein inhibitor; it prevents the action of the NS5A protein, which is required for viral replication. Voxilaprevir is a NS3/4A protease inhibitor. NS3/4A is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms of the proteins NS3, NS4A, NS4B, NS5A, and NS5B. Inhibiting this function prevents active viruses from replicating. Clinical trials of Vosevi have found that between 96% and 97% of patients who received the drug were considered cured, with no detectable virus after 12 weeks of therapy.
Like other direct-acting anti-virals for HCV, Vosevi carries a black box warning that it may reactivate hepatitis B infection, resulting in fulminant hepatitis (massive death of liver tissue and a decrease in liver size), hepatic failure, or death. It is imperative that prior to starting Vosevi all patients be tested for current or past hepatitis B infection. Vosevi's most common adverse effects are headache, tiredness, diarrhea, and nausea.
Vosevi is contraindicated with concurrent use of rifampin. Because rifampin is a strong inducer of isoenzymes in the cytochrome P-450 enzyme system, this drug combination will produce significant reductions in levels of Vosevi. Serious symptomatic bradycardia can occur if Vosevi is coadministered with amiodarone. Other drug interactions may also occur with Vosevi, including interactions with over-the-counter and herbal products.
Nurses and NPs should carefully complete a full drug history for patients prior to beginning treatment with Vosevi and assess for drug interactions using an electronic database of drug information. Vosevi is dispensed with a medication guide; nurses should teach patients about the information in the guide and the need to read the guide with each prescription. Nurses should also emphasize that, to be effective, Vosevi must be taken every day for the full duration of therapy. For complete prescribing information, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf.