Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) such as simeprevir may increase the plasma concentration of dabigatran etexilate, a substrate of the efflux transporter. When digoxin (0.25 mg once), a P-gp probe substrate, was administered with simeprevir (150 mg once a day for 7 days) in 16 healthy adults, digoxin AUC and Cmax increased by 39% and 31%, respectively.

MANAGEMENT: Product labeling advises that use of dabigatran with P-gp inhibitors in patients with severe renal impairment (CrCl less than 30 mL/min) should be avoided. In patients taking dabigatran for the treatment or prophylaxis of deep venous thrombosis (DVT) or pulmonary embolism (PE), use of dabigatran with P-gp inhibitors in moderate renal impairment (CrCl 30 to 50 mL/min) should 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.