Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 and/or P-glycoprotein may decrease the plasma concentrations of gilteritinib, which is a substrate of both the isoenzyme and the efflux transporter. When gilteritinib was coadministered with rifampin, a combined P-gp and potent CYP450 3A4 inducer, gilteritinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 30% and 70%, respectively, compared to administration of gilteritinib alone. Reduced efficacy of gilteritinib may occur. The interaction has not been studied with other, less potent inducers or lone inducers of CYP450 3A4 or P-gp.

MANAGEMENT: The potential for diminished pharmacologic effects of gilteritinib should be considered during coadministration with CYP450 3A4 and/or P-gp inducers. Alternative treatments may be required if an interaction is suspected.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.