Drug Interaction Report

MONITOR: Coadministration with simeprevir may increase the plasma concentrations and pharmacologic effects of calcium channel blockers, especially the dihydropyridines (e.g., amlodipine, felodipine, nicardipine, nifedipine, nisoldipine). The mechanism involves simeprevir inhibition of CYP450 3A4-mediated metabolism and P-glycoprotein-mediated efflux in the intestine. The interaction is not expected to occur with intravenously administered agents, since simeprevir does not affect hepatic CYP450 3A4 activity.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if calcium channel blockers are used in combination with simeprevir. Dosage reduction may be required for the calcium channel blocker, particularly if it is a dihydropyridine. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

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.