Drug Interaction Report

MONITOR: Heparin and low molecular weight heparins (LMWHs) may cause hyperkalemia. Concomitant use with potassium-sparing diuretics or aldosterone receptor antagonists may increase the risk and/or severity of hyperkalemia. Patients with renal impairment, dehydration, diabetes, adrenal disease, old age, and severe or worsening heart failure may be at greater risk.

MANAGEMENT: Caution is advised when heparin or LMWHs are used with potassium-sparing diuretics or aldosterone receptor antagonists. Serum potassium levels and renal function should be monitored regularly.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.