Drug Interaction Report

MONITOR: Coadministration with inducers of hepatic CYP450 isoenzymes may decrease the plasma concentrations of montelukast, which is metabolized by CYP450 2C8, 2C9, and 3A4 . When a single 10 mg dose of montelukast was administered in combination with phenobarbital, montelukast systemic exposure (AUC) decreased by approximately 40%.

MANAGEMENT: No dosage adjustment for montelukast is recommended when used concomitantly with CYP450 inducers. However, clinical monitoring for potentially reduced therapeutic effects may be appropriate, especially for potent inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort.

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.