Drug Interaction Report

MONITOR: Coadministration of sirolimus or tacrolimus with other drugs that are also metabolized by CYP450 3A4 may result in elevated plasma concentrations of the macrolide immunosuppressant and/or the coadministered drug(s). The mechanism is decreased drug clearance due to competitive inhibition of CYP450 3A4 activity. Although clinical data are lacking, the possibility of prolonged and/or increased pharmacologic effects of the drugs should be considered.

MANAGEMENT: Pharmacologic responses and/or plasma drug levels should be monitored more closely whenever a macrolide immunosuppressant or another substrate of CYP450 3A4 is added to or withdrawn from therapy, and the dosage(s) adjusted as necessary.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including buprenorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Patients taking buprenorphine should not consume alcohol or use medications that contain alcohol on days of buprenorphine dosing. In general, potent narcotics such as buprenorphine should not be combined with alcohol.

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.