Sofosbuvir-Velpatasvir

• Hepatitis C Virus Infection
• Chronic HCV All Genotypes
• HCV with Cirrhosis

Sofosbuvir-velpatasvir is a fixed-dose combination direct-acting antiviral (DAA) used to treat chronic hepatitis C virus (HCV) infection. This pangenotypic regimen is effective against all major HCV genotypes, simplifying treatment selection.

Mechanism of Action

The combination targets two essential viral proteins:

Sofosbuvir:

• NS5B polymerase inhibitor (nucleotide analog)
• Incorporated into viral RNA during replication
• Causes chain termination, halting viral replication
• Active against all HCV genotypes

Velpatasvir:

• NS5A inhibitor
• Blocks viral replication, assembly, and secretion
• Pangenotypic activity against HCV genotypes 1-6

Together, they provide a high barrier to resistance by targeting multiple steps in viral replication.

Available Formulations

Sofosbuvir-velpatasvir (Epclusa) is available as:

• Tablets: 400 mg/100 mg (sofosbuvir/velpatasvir)
• Oral pellets: 200 mg/50 mg and 150 mg/37.5 mg packets

Also available with voxilaprevir (Vosevi) for treatment-experienced patients.

Medical Uses

FDA-Approved Indications:

• Chronic HCV genotypes 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients ≥3 years
• Without cirrhosis or with compensated cirrhosis (Child-Pugh A)
• With decompensated cirrhosis (Child-Pugh B or C) in combination with ribavirin

Dosing Guidelines

Adults and Pediatrics ≥17 kg:

• One tablet (400 mg/100 mg) once daily with or without food

Pediatrics 3 years to <17 kg:

• Weight-based dosing with oral pellets

Treatment Duration:

• Without cirrhosis or with compensated cirrhosis: 12 weeks
• Decompensated cirrhosis: 12 weeks with ribavirin (or 24 weeks without ribavirin)

Important Safety Information

Boxed Warning:

• Hepatitis B virus (HBV) reactivation: Test for HBV before starting; monitor during and after treatment

Contraindications:

• When used with ribavirin, see ribavirin contraindications (e.g., pregnancy)

Warnings and Precautions:

• HBV reactivation can cause hepatic failure and death
• Bradycardia with amiodarone: Symptomatic bradycardia, including fatal cardiac arrest, reported
• Use with strong P-gp inducers or moderate-to-strong CYP inducers not recommended

Drug Interactions

Contraindicated/Not Recommended:

• Rifampin, rifabutin, rifapentine: Reduce sofosbuvir/velpatasvir levels
• Carbamazepine, phenytoin, phenobarbital: Reduce efficacy
• St. John's Wort: Significantly reduces levels
• Amiodarone: Serious bradycardia risk (use only with close monitoring)

Dose/Timing Modifications:

• Antacids: Separate by 4 hours
• H2-receptor antagonists: Take simultaneously or 12 hours apart at dose not exceeding famotidine 40 mg twice daily equivalent
• PPIs: Limit to omeprazole 20 mg or equivalent; take 4 hours before sofosbuvir/velpatasvir

Other:

• Digoxin: Monitor levels
• Warfarin: Monitor INR

Special Populations

• Hepatic Impairment: No adjustment for any degree; use with ribavirin for decompensated cirrhosis
• Renal Impairment: No adjustment for mild to severe; not studied in ESRD
• Pregnancy: Avoid if using ribavirin (contraindicated in pregnancy); limited data without ribavirin
• Lactation: Unknown if excreted in milk
• Pediatric: Approved for ≥3 years