Drug Interaction Report

Coadministration with moderate or potent inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations (AUC) of vibegron, which has been shown in vitro to be a substrate of the isoenzyme and transporter. Although CYP450 3A4 is the predominant enzyme in vibegron metabolism, metabolic pathways have only a minor role in the elimination of vibegron. In a phase 3 Japanese study, coadministration of vibegron (100 mg) with moderate (diltiazem) and potent (ketoconazole) inhibitors of CYP450 3A4, resulted in a 1.6- and 2.1-fold increase in vibegron AUC, respectively, which was not considered clinically significant. No dosage adjustment is recommended when vibegron is administered in combination with moderate or potent CYP450 3A4 and/or P-gp inhibitors.

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.