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 has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

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

• clotrimazole
• nystatin

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 'antifungal agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antifungal agents' category:

• clotrimazole
• nystatin

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.