Drug Interaction Report

MONITOR: Concomitant use of moderate CYP450 3A4 inducers with tretinoin (systemic) may decrease the plasma concentration of tretinoin, which is a CYP450 3A4 substrate. Reduced efficacy of tretinoin may occur. Studies document the interaction between endogenous retinoids and CYP450 3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital) showing decreased concentration of the retinoids and reduced efficacy. While clinical data specific to tretinoin are not available, similar effects may occur.

MANAGEMENT: The manufacturer recommends monitoring patients for reduced efficacy of tretinoin.

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.