What is the use of Eplerenone (an aldosterone antagonist)?

From the Guidelines

Eplerenone should be used at a starting dose of 25 mg once daily, which may be increased to 50 mg daily after a month, in patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II to IV symptoms, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The use of eplerenone in patients with HFrEF has been shown to reduce morbidity and mortality, with a high economic value, as demonstrated by the RALES, EPHESUS, and EMPHASIS-HF trials 1.

• The medication works by blocking aldosterone receptors in the kidneys, preventing sodium reabsorption and water retention while preserving potassium levels.
• Common side effects include elevated potassium levels (hyperkalemia), dizziness, and fatigue.
• Regular monitoring of potassium levels and kidney function is essential during treatment, with checks performed approximately 1 week, then 4 weeks, then every 6 months after initiating or intensifying eplerenone therapy.
• Eplerenone should be taken at the same time each day with or without food, and patients should maintain consistent potassium intake while using this medication.
• It's contraindicated in patients with severe kidney impairment, high potassium levels, or those taking strong CYP3A4 inhibitors like ketoconazole.
• The 2022 AHA/ACC/HFSA guideline recommends careful monitoring of potassium, renal function, and diuretic dosing at initiation and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Eplerenone Overview

• Eplerenone is an aldosterone receptor blocker used for the treatment of hypertension and heart failure 2, 3, 4.
• It is chemically derived from spironolactone and has a more selective action on the aldosterone receptor, which may reduce the risk of certain side effects such as gynecomastia and vaginal bleeding 3.

Clinical Uses

• Eplerenone is indicated for the treatment of mild and moderate essential hypertension in patients who cannot be treated adequately with other agents 2.
• It is also used as adjunctive therapy to reduce mortality for heart failure patients with left ventricular systolic dysfunction 2.
• Additionally, eplerenone has been shown to be effective in reducing blood pressure in patients with hypertension who are not controlled on ACE inhibitors or angiotensin II receptor blockers (ARBs) 5.

Efficacy and Safety

• Studies have demonstrated that eplerenone lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo 2.
• The most common side effect of eplerenone is hyperkalemia, which requires close monitoring in individuals with diabetes, proteinuria, heart failure, or those taking moderate CYP450 3A4 inhibitors 4.
• Eplerenone has been shown to have a protective effect on nonclassical tissues, reducing injury associated with long-term unopposed aldosterone exposure 6.

Dosage and Administration

• The daily doses of eplerenone range from 25 mg to 400 mg daily 2.
• A dose of 50 mg/day to 200 mg/day has been shown to lower blood pressure in people with primary hypertension, with no difference in effect between these doses 2.
• There is insufficient evidence to determine the effect of eplerenone on clinically meaningful outcomes such as mortality or morbidity in hypertensive patients 2.