Drug Interaction Report

GENERALLY AVOID: Coadministration with temsirolimus may potentiate the toxicities of sirolimus. Temsirolimus is metabolized primarily to sirolimus in vivo, thus concomitant administration may result in additive adverse effects, including immunosuppression, renal impairment, and pulmonary toxicity.

MANAGEMENT: Concurrent use of temsirolimus and sirolimus should be avoided.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.

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.

The recommended maximum number of medicines in the 'macrolide immunosuppressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'macrolide immunosuppressants' category:

• sirolimus
• Torisel (temsirolimus)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

The recommended maximum number of medicines in the 'mTOR inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'mTOR inhibitors' category:

• sirolimus
• Torisel (temsirolimus)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.