Glecaprevir-Pibrentasvir

• Chronic Hepatitis C (All Genotypes)
• HCV Treatment
• Direct-Acting Antiviral Therapy
• HCV/HIV Coinfection

Glecaprevir/pibrentasvir is a fixed-dose combination of two direct-acting antivirals used for the treatment of chronic hepatitis C virus (HCV) infection. This pangenotypic regimen offers highly effective treatment across all major HCV genotypes with once-daily dosing and short treatment durations.

Mechanism of Action

This combination contains two complementary direct-acting antivirals targeting different steps in the HCV replication cycle. Glecaprevir is an NS3/4A protease inhibitor that blocks the viral serine protease necessary for polyprotein processing, viral replication, and assembly of infectious viral particles. Pibrentasvir is an NS5A inhibitor that blocks the NS5A protein, which is essential for viral RNA replication, virion assembly, and secretion. The combination of these two mechanisms provides potent antiviral activity against all major HCV genotypes (pangenotypic) with a high barrier to resistance.

Available Formulations

Glecaprevir/pibrentasvir is available as film-coated tablets containing glecaprevir 100 mg and pibrentasvir 40 mg. The tablets should be taken with food. A pediatric granule formulation in oral packets (50 mg/20 mg) is available for patients weighing less than 45 kg.

Medical Uses

Glecaprevir/pibrentasvir is FDA-approved for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis; and for HCV genotype 1-infected adults with compensated cirrhosis who have been previously treated with either an NS5A inhibitor or an NS3/4A protease inhibitor but not both. It is also approved for patients with HCV/HIV coinfection.

Dosing Guidelines

The recommended dose is three tablets (glecaprevir 300 mg/pibrentasvir 120 mg) taken once daily with food. Treatment duration varies: 8 weeks for treatment-naive patients without cirrhosis (genotypes 1-6); 8-12 weeks for patients with compensated cirrhosis depending on prior treatment history; and 12-16 weeks for treatment-experienced patients depending on genotype and prior regimens. Pediatric dosing is weight-based. Treatment should be completed as prescribed without interruption.

Important Safety Information

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients; all patients should be tested for HBV before starting treatment. In patients with HBV coinfection, HBV reactivation may cause fulminant hepatitis, hepatic failure, and death. Glecaprevir/pibrentasvir is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C) and in combination with atazanavir and rifampin. Drug resistance testing is not routinely required before initiation.

Drug Interactions

Glecaprevir and pibrentasvir are substrates and inhibitors of P-gp and BCRP, and glecaprevir is a substrate and inhibitor of OATP1B1/3. Contraindicated combinations include atazanavir (significantly increases glecaprevir levels) and rifampin (significantly decreases levels). Statins may need dose limits or timing separation. Ethinyl estradiol-containing contraceptives may increase ALT elevations; use alternative contraception. Many drug interactions exist; review all concomitant medications.

Special Populations

There are no adequate data in pregnant women. Animal studies showed no adverse developmental effects. Use during pregnancy only if clearly needed. It is unknown whether glecaprevir or pibrentasvir is excreted in human breast milk; consider benefits and risks. Safety and efficacy have been established in pediatric patients 3 years and older. Elderly patients do not require dose adjustment. No dose adjustment is needed for any degree of renal impairment. The medication is contraindicated in moderate to severe hepatic impairment; no adjustment is needed for mild impairment.