Drug Interaction Report

MONITOR: Coadministration with amlodipine may increase the blood concentrations of tacrolimus. The exact mechanism of interaction is unknown but may involve inhibition of the CYP450 3A5 metabolism of tacrolimus. Isolated case reports and one crossover study involving healthy subjects have demonstrated that the AUC of tacrolimus may increase by 2.3-fold or more when taken concomitantly with amlodipine.

MANAGEMENT: Caution is advised if tacrolimus is administered concomitantly with amlodipine. Tacrolimus blood levels should be monitored frequently and the dosage adjusted accordingly, particularly following initiation or discontinuation of amlodipine therapy in patients who are stabilized on their tacrolimus regimen. Patients should be advised to contact their physician if they experience potential signs and symptoms of tacrolimus toxicity such as fever, infection, diarrhea, tremor, headache, fatigue, lethargy, and changes in motor function, mental status, or sensory function.

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.