Drug Interaction Report

Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of atogepant, which is primarily metabolized by the isoenzyme. When atogepant was administered in healthy study subjects with steady-state rifampin, a potent CYP450 3A4 inducer, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 30% and 60%, respectively. No dedicated drug interaction studies were conducted to assess concomitant use with moderate or weak CYP450 3A4 inducers. While moderate inducers can likely decrease atogepant exposure, clinically significant interaction is not expected with concomitant administration of weak inducers. No dosage adjustment of atogepant is needed when used with weak CYP450 3A4 inducers.

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.