Drug Interactions between losartan and tacrolimus

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations of tacrolimus. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Although clinical data are lacking, this interaction may result in increased risk of serious adverse reactions such as nephro- and neurotoxicity, as well as other adverse effects associated with tacrolimus such as malignancies, infections, diabetes, hyperkalemia, hypertension, and QT prolongation.

GENERALLY AVOID: Alcohol may modify the rate of tacrolimus release from extended release formulations, thereby potentially increasing the risk of serious adverse reactions.

ADJUST DOSING INTERVAL: Coadministration with food decreases the rate and extent of tacrolimus absorption. This effect is greatest after a high-fat meal.

MANAGEMENT: Patients should avoid consumption of food or drink containing grapefruit during treatment with tacrolimus. Concomitant use of tacrolimus, especially extended release formulations, with alcohol should also be avoided. Tacrolimus extended release formulations should be administered on an empty stomach, at least 1 hour before or 2 hours after a meal, and tacrolimus immediate release formulations should be taken consistently every day with or without food.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.