Drug Interaction Report

MONITOR: Coadministration with teriflunomide may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of the organic anion transporting polypeptide (OATP) 1B1 and 1B3 and/or breast cancer resistance protein (BCRP) transporters. The proposed mechanism, based on in vivo data, is decreased clearance due to teriflunomide-mediated inhibition of OATP 1B1/1B3 or BCRP transport proteins.

MANAGEMENT: Caution is advised if teriflunomide is used concomitantly with drugs that are substrates of OATP 1B1/1B3 and/or BCRP. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever teriflunomide is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of simeprevir, although the type of food does not seem to matter. In healthy study subjects, administration of simeprevir after a high-fat, high-caloric (928 kcal) breakfast increased systemic exposure (AUC) by 61% and delayed absorption by 1 hour, while administration after a normal caloric (533 kcal) breakfast increased AUC by 69% and delayed absorption by 1.5 hours.

MANAGEMENT: To ensure maximal oral absorption, simeprevir should be administered with food.