Drug Interaction Report

MONITOR: Coadministration with simeprevir may increase the plasma concentrations of daclatasvir. The proposed mechanism of interaction is simeprevir inhibition of the intestinal and/or renal efflux of daclatasvir via P-glycoprotein. When daclatasvir 60 mg once daily was administered with simeprevir 150 mg once daily, daclatasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) increased by 50%, 96% and 168%, respectively. Simeprevir Cmax, AUC and Cmin also increased by 39%, 44% and 49%, respectively, due to inhibition of OATP1B1-mediated hepatic uptake by daclatasvir.

MANAGEMENT: Caution is advised when daclatasvir is used with simeprevir. Patients should be monitored for adverse effects such as headache, fatigue, nausea, diarrhea, and serum lipase elevations.

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.