Drug Interaction Report

MONITOR: Coadministration with miconazole may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by miconazole, which is thought to be a relatively potent inhibitor of the isoenzyme. No formal drug interaction studies have been conducted with miconazole buccal tablets. Although systemic absorption following mucous membrane exposure is limited, the potential for interaction with drugs metabolized by CYP450 3A4 cannot be ruled out.

MANAGEMENT: Caution is advised if miconazole must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever miconazole is added to or withdrawn from therapy.

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.