Drug Interaction Report

MONITOR: Coadministration with drugs that are inhibitors of CYP450 3A4 may increase the blood concentrations of the macrolide immunosuppressants sirolimus and tacrolimus, both of which are metabolized by the isoenzyme.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of macrolide immunosuppressant therapy should be considered, including adverse effects such as fever, infection, diarrhea, hypokalemia, anemia, thrombocytopenia, leukopenia, and hyperlipidemia. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy.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.