Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of gilteritinib, which is a substrate of both the isoenzyme and the efflux transporter. When gilteritinib was coadministered with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, gilteritinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 20% and 120%, respectively, compared to administration of gilteritinib alone. Gilteritinib Cmax and AUC increased by approximately 16% and 40%, respectively, when coadministered with fluconazole, a moderate CYP450 3A4 inhibitor.

MANAGEMENT: Caution is advised when gilteritinib is used with CYP450 3A4 and/or P-gp inhibitors. Patients should be monitored for adverse effects such as QT interval prolongation, pancreatitis, liver transaminase and bilirubin elevations, edema, infections and stomatitis, and the gilteritinib dosage adjusted as necessary in accordance with the product labeling.

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.