Drug Interaction Report

MONITOR: Neither the leukapheresis procedure nor sipuleucel-T have been studied for use in combination with chemotherapy or immunosuppressive agents (e.g., systemic corticosteroids). Since sipuleucel-T is designed to stimulate the immune system, concurrent use of myelo- or immunosuppressive agents may alter the efficacy and/or safety of sipuleucel-T.

MANAGEMENT: Patients should be carefully evaluated to determine whether it is medically appropriate to reduce or discontinue chemotherapy or immunosuppressive agents prior to treatment with sipuleucel-T.

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.