Coadministration has not been studied but may increase simvastatin concentrations due to inhibition of P-gp and BCRP by ledipasvir. Use with caution. The dose of simvastatin should be titrated carefully and the lowest necessary dose should be used while closely monitoring for safety.

Coadministration has not studied but may increase concentrations of amlodipine or ledipasvir due to P-gp inhibition. Although a clinically significant effect of ledipasvir is considered unlikely, close monitoring of heart rate, blood pressure and for increased side effects of amlodipine is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 2C19, 3A4, 2B6, and 1A2. Ledipasvir is only a weak inhibitor of intestinal CYP3A4 in vitro. [Note, the European SmPC for clopidogrel contraindicates it use in severe hepatic impairment but the US Prescribing Information states no dose alteration.]