Drug Interaction Report

MONITOR: Limited data suggest that danazol may inhibit the CYP450 3A4 hepatic metabolism of tacrolimus. Tacrolimus serum concentrations and risk of nephrotoxicity may increase significantly.

MANAGEMENT: Until more data are available, these agents should be used concomitantly only with caution. Close monitoring of tacrolimus concentrations, blood pressure, electrolytes, and kidney function is recommended. Tacrolimus dose reductions may be required. Patients should be advised to report symptoms such as nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, paresthesias, or tremor.

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.