Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the hepatic uptake transporters organic anion transporting polypeptides (OATP) 1B1 and/or OATP 1B3 may increase the plasma concentrations of resmetirom, which has been shown to be a substrate and inhibitor of these transporters in vitro. This may increase the risk and/or severity of resmetirom-related adverse effects (e.g., hepatotoxicity, gallbladder-related adverse reactions, diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, dizziness); however, clinical data are not available.

MANAGEMENT: According to the manufacturer of resmetirom, concomitant use with inhibitors of OATP 1B1 and/or OATP 1B3 should generally be avoided.

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.