Drug Interaction Report

MONITOR: Coadministration of temsirolimus and sunitinib may increase the risk of toxicity. Dose-limiting toxicities were reported in two out of three patients in a phase I study, including grade 3/4 erythematous maculopapular rash and gout/cellulitis requiring hospitalization.

MANAGEMENT: Patients should be monitored for signs of toxicity and any reactions should be managed appropriately.

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.