Vosevi Sofosbuvir Velpatasvir and Voxilaprevir Tablets

1. Indications and Usage
Recurrent or Treatment-Naive HCV Infection: Indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) infection who are DAA-treatment experienced or treatment-naive.
Genotypes: Effective against HCV genotypes 1 through 6.
Cirrhosis Status: Applicable to patients with compensated liver cirrhosis. Not recommended for patients with decompensated cirrhosis (Child-Pugh class B or C).
2. Dosage and Administration
Route of Administration: Oral administration ONLY.
Recommended Dosage: One tablet containing 400 mg sofosbuvir, 100 mg velpatasvir, and 100 mg voxilaprevir once daily.
Treatment Duration: 12 weeks for patients with compensated cirrhosis or those failing prior DAA regimens. 8 weeks for patients without cirrhosis who are treatment-naive.
Critical Administration Instructions: Must be taken with food to ensure adequate absorption of velpatasvir and voxilaprevir.
3. Mechanism of Action
Sofosbuvir: A nucleotide analog prodrug that inhibits the HCV NS5B RNA-dependent RNA polymerase, causing chain termination during viral replication.
Velpatasvir: A pan-genotypic inhibitor of the HCV NS5A replication complex.
Voxilaprevir: A protease inhibitor that targets the HCV NS3/4A protease, preventing the cleavage of the viral polyprotein precursor.
4. Safety and Warnings
Hepatic Reactions: Severe and symptomatic hepatic decompensation and liver failure have been reported, particularly when co-administered with amiodarone or in patients with advanced liver disease.
HBV Reactivation: Hepatitis B virus (HBV) reactivation has been reported in HCV-infected patients treated with direct-acting antivirals. Patients should be screened for current or prior HBV infection.
HBsAg Seroreversion: In patients with resolved HBV infection (HBsAg negative, anti-HBc positive), HBsAg seroreversion may occur during treatment.
Contraindications: Contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease requiring dialysis.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Headache, fatigue, nausea, and diarrhea.
Clinical Research Highlights: The POLARIS clinical trials demonstrated high sustained virologic response (SVR12) rates in patients who had previously failed DAA-based regimens, including those with genotype 3 infection or cirrhosis.
6. Drug Interactions
Amiodarone: Concomitant use with sofosbuvir-containing regimens is contraindicated due to the risk of severe symptomatic bradycardia.
P-gp and BCRP Inducers: Strong inducers (e.g., rifampin, St. John’s wort) may significantly reduce sofosbuvir and velpatasvir plasma concentrations and are contraindicated.
Acid-Reducing Agents: May reduce velpatasvir solubility and absorption. Administer velpatasvir-containing products at least 2 hours before or after antacids.
7. Pharmaceutical Information
Chemical Composition: Active Ingredients: Sofosbuvir, velpatasvir, and voxilaprevir.
Appearance: Blue, capsule-shaped, film-coated tablets.
Packaging: Blister packs.
Storage: Store at controlled room temperature, protected from moisture.