Glecaprevir + Pibrentasvir

Introduction: Glecaprevir + Pibrentasvir is a fixed-dose combination medicine used for the treatment of chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis and with compensated cirrhosis (Child-Pugh A).

How it works: Glecaprevir is an HCV NS3/4A protease inhibitor which is essential for viral replication. Pibrentasvir is an HCV NS5A inhibitor essential for viral RNA replication and virion assembly.

Important Information: 3 tablets (total glecaprevir 300 mg and pibrentasvir 120 mg) taken orally once daily with food. Treatment duration is 8-16 weeks depending on genotype and treatment history.

• Chronic Hepatitis C: Genotype 1, 2, 3, 4, 5 or 6 infection - without cirrhosis or with compensated cirrhosis
• HCV genotype 1 treatment-experienced patients: who have been previously treated with a regimen containing either an NS5A inhibitor or an NS3/4A protease inhibitor, but not both

Hepatic viral infections (Hepatitis C)

NS3/4A Protease Inhibitor + NS5A Inhibitor

Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins. NS5A is a phosphoprotein that plays an essential role in replication, assembly and maturation of infectious viral proteins. Pibrentasvir blocks this interaction to inhibit the assembly of proteins and production of mature HCV particles.

Glecaprevir inhibits NS3/4A protease enzyme and Pibrentasvir inhibits NS5A protein to stop HCV replication.

Recommended Dosage:

• 3 tablets (glecaprevir 300 mg + pibrentasvir 120 mg) once daily with food

Treatment-Naïve Patients:

• Genotypes 1-6, no cirrhosis: 8 weeks
• Genotypes 1-6, compensated cirrhosis: 12 weeks

Treatment-Experienced (HCV Genotype 1):

• NS5A inhibitor prior, no cirrhosis: 16 weeks
• NS3/4A PI prior, no cirrhosis: 12 weeks

Mild Hepatic Impairment (Child-Pugh A): No dosage adjustment required

Renal Impairment: No dosage adjustment required

* Use as directed by the registered physician

Oral tablet. Take with food at the same time once daily. Swallow whole, do not chew or crush.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and follow your regular schedule.

Common Side Effects (>10%):

• Headache (9-17%)
• Fatigue (11-14%)
• Nausea (6-12%)

Other (1-10%):

• Diarrhea (3-7%)
• Increased bilirubin (3.5%)
• Pruritus (7%)

Precautions:

• Hepatitis B virus reactivation may occur in HCV/HBV coinfected patients.
• Test all patients for HBV infection before initiation of HCV treatment.

Contraindications:

• Severe hepatic impairment (Child-Pugh C)
• Coadministration with atazanavir or rifampin

Drug Interactions:

• Coadministration is contraindicated with atazanavir or rifampin
• Coadministration is not recommended with carbamazepine, efavirenz, or St. John's wort

Food Interactions:

• Should be taken with food (for better absorption)

Use in Pregnancy: No adequate human data are available to establish whether or not this poses a risk to pregnancy outcomes.

Use in Lactation: Unknown if distributed in human breast milk. When administered to lactating rodents, glecaprevir and pibrentasvir were present in milk.

Pediatric Use: Safety and efficacy in pediatric patients have not been established.

Geriatric Use: No specific dosage adjustment is necessary for elderly patients.

Renal Impairment: No dosage adjustment required in mild, moderate or severe renal impairment (including patients on dialysis).

Hepatic Impairment: Mild (Child-Pugh A): No dosage adjustment required. Moderate (Child-Pugh B): Not recommended. Severe (Child-Pugh C): Contraindicated.

Overdose: Monitor patient for any signs and symptoms of toxicities. Appropriate symptomatic treatment should be instituted immediately. Glecaprevir and pibrentasvir are not significantly removed by hemodialysis.

Storage: Store at or below 30°C.

Glecaprevir + Pibrentasvir Tablet