Mavyret (Glecaprevir/Pibrentasvir): A Comprehensive Overview
Mavyret is a fixed-dose combination of glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) that provides a highly effective pangenotypic treatment for chronic hepatitis C virus (HCV) infection in patients with or without compensated cirrhosis. 1
Indications and Usage
Mavyret is indicated for:
- Treatment of adult and pediatric patients 3 years and older with chronic HCV genotype 1,2,3,4,5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)
- Treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both 1
Dosage and Administration
Adults and Adolescents ≥12 years or ≥45 kg:
- Standard dosage: Three tablets (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) taken once daily with food 1
Treatment Duration:
Treatment-naïve patients (all genotypes):
- Without cirrhosis: 8 weeks
- With compensated cirrhosis: 8 weeks
Treatment-experienced patients:
- Prior NS5A inhibitor without NS3/4A PI (genotype 1): 16 weeks
- Prior NS3/4A PI without NS5A inhibitor (genotype 1): 12 weeks
- Prior PRS treatment (genotypes 1,2,4,5,6): 8-12 weeks
- Prior PRS treatment (genotype 3): 16 weeks 1
Efficacy
Mavyret demonstrates exceptional efficacy across all HCV genotypes:
In patients without cirrhosis, 8 weeks of treatment achieved SVR12 rates of:
In patients with compensated cirrhosis, the SVR12 rate was 99.4% with 12 weeks of treatment 4
In patients with severe renal impairment (CKD stage 4 or 5), the SVR12 rate was 98-99% 5
Pharmacology
Mechanism of Action: Combination of direct-acting antiviral agents targeting HCV NS3/4A protease (glecaprevir) and NS5A (pibrentasvir) 1
Pharmacokinetics:
- Absorption enhanced with food (83-163% increase for glecaprevir)
- Primarily eliminated through biliary-fecal route
- Half-lives: glecaprevir ~6 hours, pibrentasvir ~23 hours 1
Special Populations
Renal Impairment
- No dose adjustment required for any degree of renal impairment, including patients on hemodialysis
- Mavyret is the treatment of choice for patients with chronic hepatitis C and stage 4 or 5 CKD (including those on hemodialysis) 5
Hepatic Impairment
- Safe for use in patients with compensated (Child-Pugh A) cirrhosis
- Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation 1
Safety and Adverse Events
The most commonly reported adverse events include:
- Headache
- Fatigue
- Upper respiratory tract infection 4
Serious adverse events are rare, occurring in <1-3% of patients 4
Important Warnings
Boxed Warning: Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV, which can result in fulminant hepatitis, hepatic failure, and death. All patients should be tested for HBV infection before initiating treatment 1
Drug Interactions
Mavyret is contraindicated with:
- Atazanavir
- Rifampin 1
Other significant interactions include:
- Carbamazepine
- Efavirenz-containing regimens
- St. John's wort 5
Clinical Considerations
- Mavyret offers a shorter treatment duration (8 weeks) for most patients compared to other regimens
- High barrier to resistance
- Pangenotypic activity allows treatment without genotype testing in many scenarios
- Safe and effective in special populations including those with HIV coinfection 6
When selecting Mavyret for HCV treatment, consider the patient's treatment history, presence of cirrhosis, renal function, and potential drug interactions to determine the optimal treatment duration and ensure safety.