Summary

The combination of eplerenone and losartan increases the risk of hyperkalemia (elevated potassium levels) due to their complementary mechanisms of potassium retention. Both medications are commonly used in cardiovascular conditions but require careful monitoring when used together.

Introduction

Eplerenone is a selective aldosterone receptor antagonist (potassium-sparing diuretic) primarily used to treat heart failure and hypertension by blocking aldosterone's effects on sodium and potassium balance. Losartan is an angiotensin receptor blocker (ARB) that treats hypertension and heart failure by blocking angiotensin II receptors, which indirectly affects potassium levels by reducing aldosterone production.

Mechanism of Interaction

The interaction occurs through complementary effects on the renin-angiotensin-aldosterone system (RAAS). Losartan blocks angiotensin II receptors, reducing aldosterone secretion and decreasing potassium excretion. Eplerenone directly blocks aldosterone receptors in the kidneys, further preventing potassium elimination. This dual mechanism significantly increases potassium retention, potentially leading to dangerous hyperkalemia.

Risks and Symptoms

The primary risk is hyperkalemia (serum potassium >5.5 mEq/L), which can cause life-threatening cardiac arrhythmias, muscle weakness, and paralysis. Risk factors include kidney disease, diabetes, dehydration, advanced age, and concurrent use of other potassium-retaining medications or supplements. The interaction is considered clinically significant and requires active management.

Management and Precautions

Monitor serum potassium levels before initiation and regularly during treatment (weekly initially, then monthly). Check kidney function (creatinine, eGFR) as impaired renal function increases hyperkalemia risk. Consider dose reduction of either medication if potassium levels rise above 5.0 mEq/L. Educate patients to avoid potassium supplements and salt substitutes. Discontinue one or both medications if potassium exceeds 5.5 mEq/L or if symptoms of hyperkalemia develop.

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.

Losartan interactions with food and lifestyle

Losartan may interact with potassium-rich foods and salt substitutes containing potassium. Patients should avoid excessive consumption of high-potassium foods (such as bananas, oranges, potatoes, and spinach) and potassium-containing salt substitutes, as this combination may lead to dangerous elevations in blood potassium levels (hyperkalemia). Alcohol consumption should be limited as it may enhance the blood pressure-lowering effects of losartan, potentially causing excessive drops in blood pressure, dizziness, or fainting. Patients should also maintain adequate hydration and avoid becoming dehydrated, especially during hot weather or exercise, as dehydration can increase the risk of kidney problems when taking losartan.