glecaprevir + pibrentasvir: clinical use

Prescribing considerations

• Initiate and monitor under a clinician experienced in hepatitis C management.
• Establish liver disease severity and review previous exposure to NS3/4A or NS5A inhibitors.
• Complete medication reconciliation, including HIV therapy, contraception, statins and herbal products.
• Renal impairment, dialysis, transplantation and HIV coinfection require individual specialist assessment.

Contraindications and cautions

• Hypersensitivity to either active substance or an excipient.
• Severe hepatic impairment (Child-Pugh C); use is also not recommended in moderate hepatic impairment.
• Concomitant atazanavir, atorvastatin, simvastatin, dabigatran etexilate or ethinylestradiol-containing products.
• Strong P-gp/CYP3A inducers including rifampicin, carbamazepine, St John’s wort, phenobarbital, phenytoin and primidone.

Monitoring

• Screen for hepatitis B before starting; monitor and manage HBV/HCV coinfection because reactivation can occur.
• Use virological and liver blood tests to assess response and safety.
• Monitor glucose closely in people with diabetes, particularly early in treatment.
• Monitor INR more closely with vitamin K antagonists.
• Use therapeutic drug monitoring when clinically indicated for interacting immunosuppressants.

Clinical pharmacology

Glecaprevir inhibits HCV NS3/4A protease and pibrentasvir inhibits NS5A. Both act across major HCV genotypes, are highly protein-bound and are eliminated mainly through the biliary/faecal route. They also inhibit transporters including P-gp, BCRP and OATP1B1/3, accounting for several important interactions.

Formulation and product differences

• Film-coated tablets contain 100 mg glecaprevir and 40 mg pibrentasvir and must be swallowed whole with food.
• Coated-granule sachets contain 50 mg glecaprevir and 20 mg pibrentasvir and are intended for eligible younger children according to age and weight.
• Granules are mixed with suitable soft food and swallowed immediately; they must not be crushed, chewed or administered through a feeding tube.
• Tablets and granules have different pharmacokinetic profiles and are not interchangeable.

Sachet

Route: Oral

Strengths: 50 mg + 20 mg

Tablet

Route: Oral

Strengths: 100 mg + 40 mg