Drug Interaction Report

MONITOR: Limited data suggest that coadministration with green tea may increase the plasma concentrations of tacrolimus. The mechanism of interaction has not been established. Although tacrolimus is primarily metabolized by CYP450 3A4, clinical studies have not found significant effects of green tea catechins on CYP450 isoenzymes. The interaction was suspected in a 58-year-old male kidney transplant recipient whose tacrolimus levels approximately doubled from previous levels during routine therapeutic monitoring a couple days after he started consuming green tea. Tacrolimus levels gradually returned to normal within a few weeks after discontinuing green tea consumption. The patient was genotyped and found to be a poor metabolizer of CYP450 3A4. No information was provided on the type or quantity of green tea consumed by the patient.

MANAGEMENT: Caution may be advisable when tacrolimus is taken concomitantly with green tea or green tea extracts. Dosing reduction of tacrolimus and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.

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.