This medicine is a fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor. It is used to treat adults with chronic HCV infection of genotype 1, 2, 3, 4, 5, or 6, both without cirrhosis and with compensated cirrhosis (Child-Pugh A). It is also indicated for adults with HCV genotype 1 who have previously received treatment containing either an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.

Glecaprevir is an inhibitor of the HCV NS3/4A protease, an enzyme required for breaking down the HCV polyprotein into mature NS3, NS4A, NS4B, NS5A, and NS5B proteins. These proteins, especially NS3, are essential for viral replication. The N-terminal of NS3 has serine protease activity, while the C-terminal contains an RNA helicase that uses energy from NTP to unwind viral RNA during replication. NS4A acts as a cofactor for NS3, helping it locate within the cell and regulating its activity. Glecaprevir blocks the NS3/4A protease, disrupting the viral life cycle by preventing the cleavage and processing of viral proteins.

Pibrentasvir targets NS5A, a phosphoprotein critical for replication, assembly, and maturation of viral proteins. The phosphorylated form of NS5A interacts with the viral capsid (core) protein. By blocking this interaction, pibrentasvir prevents the formation of mature HCV particles. NS5A also helps form the HCV replicase complex, supporting RNA replication.

Testing Prior to the Initiation of Therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc.

Recommended dosage: Three tablets (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) taken orally once daily with food.

See recommended treatment duration in tables below-

Treatment-Naïve Patients: HCV Genotype 1, 2, 3, 4, 5, or 6

• No Cirrhosis: 8 weeks
• Compensated Cirrhosis (Child-Pugh A): 12 weeks

Treatment-Experienced Patients: HCV Genotype 1

• Patients Previously Treated With a Regimen Containing: An NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor
• No Cirrhosis: 16 weeks
• Compensated Cirrhosis (Child-Pugh A): 16 weeks

Treatment-Experienced Patients: HCV Genotype 1

• Patients Previously Treated With a Regimen Containing: An NS3/4A PI without prior treatment with an NS5A inhibitor
• No Cirrhosis: 12 weeks
• Compensated Cirrhosis (Child-Pugh A): 12 weeks

Treatment-Experienced Patients: HCV Genotype 1, 2, 4, 5 or 6

• Patients Previously Treated With a Regimen Containing: PRS
• No Cirrhosis: 8 weeks
• Compensated Cirrhosis (Child-Pugh A): 12 weeks

Treatment-Experienced Patients: HCV Genotype 3

• Patients Previously Treated With a Regimen Containing: PRS
• No Cirrhosis: 16 weeks
• Compensated Cirrhosis (Child-Pugh A): 16 weeks

Carbamazepine, efavirenz, and St. John’s wort may reduce the blood levels of glecaprevir and pibrentasvir. Therefore, taking carbamazepine, efavirenz-containing treatments, or St. John’s wort together with this medicine is not recommended.

This medicine should not be used in patients with severe liver problems (Child-Pugh C). It is also contraindicated to take it together with atazanavir or rifampin.

In patients taking this medicine, the most commonly reported side effects (occurring in more than 10% of patients) are headache and fatigue.

There is not enough human data to determine whether this medicine is safe during pregnancy. It is also unknown whether the components of this medicine pass into human breast milk, affect milk production, or impact a breastfeeding infant. Studies in lactating rodents showed that the components were present in milk but did not affect the growth or development of the pups. Decisions about using this medicine during breastfeeding should weigh the benefits of breastfeeding, the mother’s medical need for the medicine, and any potential risks to the child from the medicine or the mother’s underlying condition.

Risk of Hepatitis B Virus (HBV) Reactivation: Before starting HCV treatment, all patients should be tested for current or past HBV infection. Patients who have both HCV and HBV should be closely monitored for HBV reactivation or hepatitis flare during treatment and after treatment ends. Appropriate management for HBV infection should be provided based on clinical needs.

Renal Impairment: No dose adjustment is needed for patients with mild, moderate, or severe kidney problems, including those on dialysis.

Hepatic Impairment: No dose adjustment is required for patients with mild liver impairment (Child-Pugh A). This medicine is not recommended for patients with moderate liver impairment (Child-Pugh B), as safety and effectiveness have not been established. It is contraindicated in patients with severe liver impairment (Child-Pugh C).

In case of an overdose, the patient should be closely monitored for any signs or symptoms of toxicity. Appropriate supportive or symptomatic treatment should be started immediately. Glecaprevir and pibrentasvir are not significantly removed by hemodialysis.

Hepatic viral infections (Hepatitis C)

Store the medicine at or below 30°C, in a cool and dry place, away from direct sunlight.