Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of gilteritinib, which is primarily metabolized by the isoenzyme. When gilteritinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, gilteritinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 20% and 120%, respectively, compared to administration of gilteritinib alone. Increased exposure to gilteritinib may increase the risk of serious adverse effects such as QT interval prolongation, pancreatitis, liver transaminase and bilirubin elevations, edema, infections, and stomatitis.

MANAGEMENT: Concomitant use of gilteritinib with potent CYP450 3A4 inhibitors should generally be avoided. Alternative agents with no or minimal CYP450 3A4 inhibitory potential are recommended whenever possible. Otherwise, close monitoring for increased adverse effects is advisable, including more frequent ECG monitoring. Gilteritinib treatment should be interrupted or dosage reduced in patients with serious or life-threatening toxicity in accordance with the product labeling.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.