ledipasvir + sofosbuvir: clinical use

Prescribing considerations

• Confirm HCV genotype, previous antiviral exposure, cirrhosis and transplant status.
• Review prescribed, non-prescribed and herbal products for interactions.
• Screen for current or previous hepatitis B infection.
• Assess renal function, particularly in severe impairment or with tenofovir disoproxil.
• Apply ribavirin’s separate safety requirements when relevant.

Contraindications and cautions

• Hypersensitivity to either active ingredient or a formulation excipient
• Concomitant rosuvastatin
• Concomitant strong intestinal P-glycoprotein inducers, including carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St John’s wort

Monitoring

• HCV RNA response and relevant liver tests
• HBV markers and appropriate follow-up where indicated
• Glucose in people with diabetes
• INR with vitamin K antagonists
• Renal function and tenofovir-associated adverse effects with interacting HIV regimens
• Heart rate and rhythm if concurrent or recent amiodarone use is unavoidable

Clinical pharmacology

Ledipasvir inhibits HCV NS5A, intestinal P-glycoprotein and BCRP. Sofosbuvir is converted intracellularly into an active triphosphate that inhibits NS5B RNA-dependent RNA polymerase by chain termination; clinically important CYP-mediated interactions are not expected.

Formulation and product differences

• Film-coated tablets should be swallowed whole and not chewed or crushed.
• Coated granules can be taken directly, with water, or with non-acidic soft food and must not be chewed.
• The tablet and granule formulations contain lactose and sunset yellow FCF, which may matter in intolerance or allergy assessment.

Tablet

Route: Oral

Strengths: 90 mg + 400 mg