Drug Interaction Report

ADJUST DOSE: Bexarotene is structurally related to vitamin A and may theoretically share some of the same toxicities. However, unlike vitamin A and other retinoids that bind retinoic acid receptors, bexarotene selectively activates retinoid X receptors, which can produce biologic activity distinct from the others.

MANAGEMENT: Patients should be advised to limit vitamin A supplements to 15,000 IU/day to avoid potential additive toxic effects.

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.

The recommended maximum number of medicines in the 'retinoic acid derivatives' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'retinoic acid derivatives' category:

• A-25 (vitamin a)
• bexarotene

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.