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.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.