Epclusa Sofosbuvir and Velpatasvir Tablets

1. Indications and Usage
Treatment of Chronic Hepatitis C Virus (HCV) Infection:
Indicated for the treatment of adult and pediatric patients (3 years of age and older and weighing at least 15 kg) with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A).
Decompensated Cirrhosis:
Indicated for the treatment of adult patients with HCV genotype 1, 2, 3, 4, 5, or 6 infection and decompensated cirrhosis (Child-Pugh B), to be used in combination with ribavirin.
2. Dosage and Administration
Recommended Dosage:
Adults and Adolescents (≥12 years or ≥35 kg): One tablet (400 mg sofosbuvir and 100 mg velpatasvir) orally once daily.
Treatment Duration: Typically 12 weeks for patients without cirrhosis or with compensated cirrhosis. 12 weeks in combination with ribavirin for patients with decompensated cirrhosis.
Administration Instructions:
Can be taken with or without food.
Swallow the tablet whole; do not chew or crush.
Missed Dose:
If a dose is missed and it is less than 18 hours since the usual time of dosing, take the dose as soon as possible and resume the normal schedule.
If more than 18 hours have passed, skip the missed dose and resume the normal schedule. Do not take a double dose.
3. Mechanism of Action
Direct-Acting Antiviral (DAA) Combination:
Sofosbuvir and velpatasvir are direct-acting antiviral agents that target different steps in the HCV life cycle.
Sofosbuvir:
A nucleotide analog inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication.
Velpatasvir:
An HCV NS5A (non-structural protein 5A) inhibitor, which is required for viral RNA replication and virion assembly.
Pan-Genotypic Activity:
The combination provides a pangenotypic treatment regimen, effective against all major HCV genotypes (1-6).
4. Safety and Warnings
Hepatitis B Virus (HBV) Reactivation:
Test all patients for evidence of current or prior HBV infection before initiating treatment. HBV reactivation has been reported in patients coinfected with HCV and HBV who were treated with HCV direct-acting antivirals.
Bradycardia with Concomitant Amiodarone:
Serious symptomatic bradycardia may occur in patients taking amiodarone concomitantly with sofosbuvir-containing regimens. Concomitant use is not recommended.
Post-Treatment Safety Monitoring:
Patients should be monitored for adverse events after treatment is completed.
Pregnancy and Lactation:
If co-administered with ribavirin, the pregnancy precautions and contraindications for ribavirin apply.
5. Adverse Reactions
Most Common:
Fatigue, headache, nausea, diarrhea, and insomnia.
Other:
Elevated bilirubin, anemia (when combined with ribavirin), and increased hepatic enzymes.
6. Drug Interactions
P-glycoprotein (P-gp) and CYP Inducers:
Concomitant use with strong P-gp inducers (e.g., rifampin, St. John’s wort) or potent CYP inducers (e.g., carbamazepine, phenytoin) is contraindicated as it significantly decreases sofosbuvir and velpatasvir plasma concentrations.
Acid-Reducing Agents:
Velpatasvir solubility decreases as pH increases. Concomitant use with proton pump inhibitors (PPIs) or H2-receptor antagonists may decrease velpatasvir plasma concentrations. Follow specific dosing separation recommendations.
Statins:
Concomitant use may increase plasma concentrations of certain statins (e.g., rosuvastatin), increasing the risk of myopathy.
Amiodarone:
Serious symptomatic bradycardia may occur. Concomitant use is not recommended.
7. Pharmaceutical Information
Chemical Name:
Sofosbuvir: Isopropyl (2S)-2-[[[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate.
Velpatasvir: (11S,16B,21aS,24aR)-11-(acetyloxy)-24a-(4-(4-((2-(bis(4-chlorophenyl)methoxy)ethyl)amino)-1,3,5-triazin-2-yl)phenyl)-16-(3-(3-fluorophenyl)oxetan-3-yl)-5-chloro-21a-methyl-11,14,19,22-tetraoxo-13,16-diazatetracyclo