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.

GENERALLY AVOID: Coadministration of protein-bound sirolimus intravenous suspension with grapefruit juice may increase the systemic exposure to sirolimus. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of sirolimus by certain compounds present in grapefruit. However, grapefruit juice primarily inhibits CYP450 3A4-mediated first-pass metabolism in the gut wall and may have limited effects on medications that are not administered orally. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with protein-bound sirolimus.