Summary

The combination of eplerenone and lisinopril significantly increases the risk of hyperkalemia (elevated potassium levels) due to their complementary mechanisms of potassium retention. This interaction requires careful monitoring and may necessitate dose adjustments or alternative treatment strategies.

Introduction

Eplerenone is a selective aldosterone receptor antagonist primarily used to treat heart failure and hypertension by blocking aldosterone's effects on sodium and potassium balance. Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor commonly prescribed for hypertension, heart failure, and diabetic nephropathy by reducing angiotensin II production and decreasing aldosterone secretion.

Mechanism of Interaction

Both eplerenone and lisinopril affect the renin-angiotensin-aldosterone system (RAAS) in ways that promote potassium retention. Lisinopril reduces aldosterone production by inhibiting ACE and decreasing angiotensin II formation, while eplerenone directly blocks aldosterone receptors in the kidneys. This dual mechanism significantly impairs the kidney's ability to excrete potassium, leading to additive effects on serum potassium levels.

Risks and Symptoms

The primary risk of combining eplerenone and lisinopril is severe hyperkalemia (serum potassium >5.5 mEq/L), which can cause life-threatening cardiac arrhythmias, muscle weakness, and paralysis. Patients with kidney disease, diabetes, dehydration, or those taking other potassium-sparing medications face elevated risk. Additional concerns include acute kidney injury, particularly in patients with pre-existing renal impairment or volume depletion.

Management and Precautions

Close monitoring of serum potassium and kidney function is essential, with baseline measurements and follow-up testing within 1 week of initiation, then regularly thereafter. Consider starting with lower doses and titrating carefully. Patients should avoid potassium supplements and salt substitutes containing potassium. Maintain adequate hydration and monitor for signs of hyperkalemia. In high-risk patients, consider alternative agents or more frequent monitoring intervals.

Eplerenone interactions with food and lifestyle

Eplerenone should be taken with or without food as food does not significantly affect absorption. However, patients should avoid salt substitutes containing potassium and limit high-potassium foods (such as bananas, oranges, potatoes, and spinach) as eplerenone can increase potassium levels in the blood. Grapefruit juice should be avoided as it may increase eplerenone levels in the body by inhibiting CYP3A4 metabolism. Alcohol consumption should be limited as it may enhance the blood pressure-lowering effects of eplerenone and increase the risk of dizziness or fainting.

Lisinopril interactions with food and lifestyle

Lisinopril may interact with potassium-containing salt substitutes and potassium supplements, potentially leading to dangerous elevations in blood potassium levels (hyperkalemia). Patients should consult their healthcare provider before using salt substitutes or taking potassium supplements while on lisinopril. Alcohol consumption may enhance the blood pressure-lowering effects of lisinopril, potentially causing excessive drops in blood pressure, dizziness, or fainting. Patients should limit alcohol intake and monitor for symptoms of low blood pressure when drinking alcohol while taking lisinopril.