Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of ensartinib, which is primarily metabolized via the isoenzyme in vitro. Clinical data characterizing the extent of this interaction and data with less potent inducers are not available.

MANAGEMENT: Concomitant use of ensartinib with moderate to potent inducers of CYP450 3A4 should generally be avoided. The possibility of diminished therapeutic effects should be considered. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.