Drug Interactions between amoxicillin / clarithromycin / vonoprazan and bexarotene

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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.