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.

ADJUST DOSING INTERVAL: Food increases the systemic exposure to both telotristat ethyl and its active metabolite, telotristat. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dose) with a high-fat meal, telotristat ethyl peak plasma concentration (Cmax) and systemic exposure (AUC) were 112% and 264% higher, respectively, compared to administration under fasted conditions. The Cmax and AUC values for telotristat were also increased by 47% and 33%, respectively. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase has been shown to be approximately 29 times higher than that of the parent drug.

MANAGEMENT: Telotristat ethyl should be administered with food.