Drug Interaction Report

MONITOR: There are no data regarding the use of live, unattenuated Adenovirus Type 4 and Type 7 vaccine during treatment with immunosuppressive therapies, including alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, and long-term topical or inhaled corticosteroids. It is not known whether immunosuppressed patients may have an increased risk of adverse reactions or a decreased or suboptimal immunologic response to the vaccine.

MANAGEMENT: The safety and efficacy of live, unattenuated Adenovirus Type 4 and Type 7 vaccine have not been established in patients receiving immunosuppressive therapies. Caution is advised.

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.