Drug Interaction Report

MONITOR: Coadministration of tacrolimus with ACE inhibitors or angiotensin II receptor antagonists may increase the risk of hyperkalemia associated with the use of these drugs, particularly in patients with renal impairment. Mild to severe hyperkalemia was reported in 31% and 21% of kidney transplant recipients and in 45% and 13% of liver transplant recipients treated with tacrolimus in U.S. and European randomized trials, respectively, and in 8% of heart transplant recipients in a European randomized trial.

MANAGEMENT: Serum potassium levels and renal function should be monitored regularly when tacrolimus is used in combination with ACE inhibitors or angiotensin II receptor antagonists. Particular caution is warranted in patients with renal impairment, diabetes, old age, severe or worsening heart failure, or dehydration. Patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat.

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.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.