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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of suvorexant. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, alcohol may increase the risk of cognitive and complex behavioral changes associated with the use of hypnotics including suvorexant, such as amnesia, anxiety, hallucinations, sleep-driving, and other neuropsychiatric symptoms.

ADJUST DOSE: Grapefruit juice may significantly increase the plasma concentrations of suvorexant. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

ADJUST DOSING INTERVAL: Administration with or soon after a meal may delay the gastrointestinal absorption of suvorexant. According to the product labeling, administration of suvorexant with a high-fat meal resulted in no meaningful change in peak plasma concentration (Cmax) or systemic exposure (AUC), but a delay in Tmax of approximately 1.5 hours.

MANAGEMENT: Concomitant use of suvorexant with alcohol should be avoided. Patients should be advised not to use suvorexant if they had alcohol that evening or before bed. Grapefruit juice should preferably be avoided; otherwise, the recommended dose of suvorexant is 5 mg when used with grapefruit juice and should not exceed 10 mg. Suvorexant may be taken with or without food; however, for faster sleep onset, suvorexant should not be administered with or soon after a meal.