Drug Interaction Report

MONITOR CLOSELY: Coadministration with clotrimazole may significantly increase the oral bioavailability of sirolimus and tacrolimus. The proposed mechanism is clotrimazole inhibition of sirolimus and tacrolimus metabolism via intestinal CYP450 3A4. In 17 post-transplant patients treated with clotrimazole troches (10 mg three times a day), significantly higher blood tacrolimus trough levels were observed by the third day compared to 18 patients treated with nystatin (5 mL four times a day). Levels were still higher in the clotrimazole group by day 7, although mean tacrolimus doses were significantly lower than in the nystatin group. The interaction has not been reported with sirolimus, although it should be expected based on its similar pharmacokinetic profile to tacrolimus.

MANAGEMENT: Caution is advised if sirolimus or tacrolimus is prescribed with clotrimazole. Immunosuppressant blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation, discontinuation, or change of dosage of clotrimazole in patients who are stabilized on their antirejection regimen.

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.