Drug Interactions between bexarotene and ixazomib

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.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of ixazomib. A food effect study found that administration of a single 4 mg dose of ixazomib with a high-fat meal decreased ixazomib peak plasma concentration (Cmax) by 69% and systemic exposure (AUC) by 28%.

MANAGEMENT: Ixazomib should be taken at least one hour before or two hours after eating. On days when both ixazomib and dexamethasone are administered, advise patients to separate dosing times, since dexamethasone should be taken with food while ixazomib should be taken on an empty stomach.