Drug Interaction Report

MONITOR: Higher dosages of lipid-lowering agents may be required during concomitant administration of sirolimus or temsirolimus. Dose-related serum lipid abnormalities, including but not limited to increased serum cholesterol and triglycerides, have been frequently reported in patients treated with sirolimus or temsirolimus.

MANAGEMENT: Close clinical monitoring of serum cholesterol and triglycerides is recommended if sirolimus or temsirolimus is prescribed to patients receiving lipid-lowering agents. Modification of the antihyperlipidemic regimen or dosages may be necessary.

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.