Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentration and pharmacologic effects of ritlecitinib. The proposed mechanism is increased clearance of ritlecitinib due to induction of the CYP450 3A4 isoenzyme, one of the pathways of elimination of ritlecitinib. When a single 50 mg dose of ritlecitinib was administered in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of ritlecitinib decreased by approximately 25% and 44%, respectively, compared to ritlecitinib administered alone. Data are not available of other, less potent inducers.

MANAGEMENT: Caution is advised when ritlecitinib is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.

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.