Drug Interaction Report

Theoretically, coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of rivaroxaban, which is a substrate of the isoenzyme as well as the efflux transporter. In a pharmacokinetic study, administration of a single 20 mg dose of rivaroxaban with the potent CYP450 3A4 and P-gp inducer rifampin (titrated up to 600 mg once daily) resulted in approximately 22% and 50% decreases in mean rivaroxaban peak plasma concentration (Cmax) and system exposure (AUC), respectively, with parallel decreases in its pharmacodynamic effects. The effects of less potent inducers of either CYP450 3A4 or P-gp have not been studied.

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.