Sofosbuvir + Velpatasvir + Voxilaprevir

Indications

Sofosbuvir + Velpatasvir + Voxilaprevir is used for: Indicated for retreatment of, chronic hepatitis C virus (HCV) infection

Adult Dose

Hepatitis C Indicated for retreatment of chronic hepatitis C virus (HCV) infection in adults with genotype 1, 2, 3, 4, 5, or 6 previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) PO qDay for 12 weeks Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Moderate or severe (Child-Pugh B or C): Not recommended owing to higher voxilaprevir exposure

Child Dose

Renal Dose

Renal impairment Mild or moderate: No dosage adjustment required Severe (eGFR <30 mL/min/1.73 m²) or ESRD: Not recommended owing to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite

Administration

Take with food

Contra Indications

Rifampin; significantly decreases sofosbuvir, velpatasvir, and voxilaprevir serum concentrations

Precautions

Hepatitis B reactivation Test all patients for evidence of current or prior HBV infection before initiating HBV reactivation 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 resulted in fulminant hepatitis, hepatic failure, and death

Pregnancy-Lactation

Pregnancy No adequate human data are available to establish whether or not sofosbuvir/velpatasvir/voxilaprevir poses a risk to pregnancy outcomes Animal reproduction studies No evidence of adverse developmental outcomes was observed with sofosbuvir, velpatasvir, or voxilaprevir at exposures greater than those in humans at the recommended human dose Lactation Unknown if distributed in human breast milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Serious symptomatic bradycardia may occur in patients taking amiodarone with sofosbuvir-containing regimens, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities, and/or advanced liver disease Coadministration with amiodarone not recommended Coadministration of amiodarone with sofosbuvir/velpatasvir/voxilaprevir may result in serious symptomatic bradycardia; coadministration not recommended; if coadministration is required, cardiac monitoring recommended Dabigatran levels are increased by sofosbuvir/velpatasvir/voxilaprevir; dabigatran dose may require modifications, particularly with coexisting moderate renal impairment Carbamazepine, phenytoin, phenobarbital, and oxcarbazepine decrease sofosbuvir, velpatasvir, and voxilaprevir levels; coadministration not recommended Atazanavir or lopinavir increases voxilaprevir levels; coadministration not recommended Tipranavir/ritonavir decreases sofosbuvir and velpatasvir levels; coadministration not recommended; effect on voxilaprevir is unknown Efavirenz decreases velpatasvir and voxilaprevir levels; coadministration not recommended Tenofovir DF is increased by sofosbuvir/velpatasvir/voxilaprevir; monitor for adverse effects, particularly renal toxicity

Adverse Effects

Side effects of Sofosbuvir + Velpatasvir + Voxilaprevir : >10% Headache (21-23%) Fatigue (17-19%) Diarrhea (13-14%) Nausea (10-13%) 1-10% Asthenia (4-6%) Insomnia (3-6%)

Mechanism of Action

Sofosbuvir: Inhibitor of HCV NS5B RNA-dependent polymerase; its inhibition, in turn, suppresses viral replication Velpatasvir: Pangenotypic HCV NS5A inhibitor; the NS5A protein is required for viral replication Voxilaprevir: Pangenotypic NS3/4A protease inhibitor, which is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms and is essential for viral replication