Usage
Eplerenone is prescribed for:
- Hypertension: Management of mild to moderate essential hypertension, alone or in combination with other antihypertensive agents.
- Heart Failure Post-Myocardial Infarction (MI): To improve survival and reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (HF) in stable patients with left ventricular systolic dysfunction (LVEF ≤ 40%) and clinical evidence of HF after an acute MI.
- Chronic Heart Failure: To reduce the risk of CV mortality and morbidity (hospitalization for HF) in patients with New York Heart Association (NYHA) class II chronic HF and left ventricular systolic dysfunction (EF ≤30%)
Pharmacological Classification: Selective aldosterone receptor antagonist.
Mechanism of Action: Eplerenone competitively binds to the mineralocorticoid receptor, blocking the binding of aldosterone. This inhibits aldosterone’s effects on sodium and water retention, mitigating its contribution to increased blood pressure and cardiac remodeling.
Alternate Names
- International Nonproprietary Name (INN): Eplerenone
- Brand Names: Inspra
How It Works
Pharmacodynamics: Eplerenone selectively binds to mineralocorticoid receptors in the heart, kidneys, and blood vessels, antagonizing the effects of aldosterone. This reduces sodium reabsorption, promoting diuresis and lowering blood pressure without affecting potassium levels as significantly as non-selective aldosterone antagonists (e.g., spironolactone).
Pharmacokinetics:
- Absorption: Well-absorbed orally. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized by CYP3A4.
- Elimination: Excreted primarily via feces and to a lesser extent in urine. Half-life is approximately 3-6 hours.
Mode of Action: Eplerenone’s mode of action involves competitive antagonism of aldosterone at the mineralocorticoid receptor. This prevents aldosterone-mediated gene transcription, thereby reducing the expression of proteins involved in sodium and water reabsorption.
Receptor Binding: Selectively binds to the mineralocorticoid receptor.
Elimination Pathways: Predominantly hepatic metabolism through CYP3A4, with biliary/fecal excretion as the primary route of elimination. A smaller portion is eliminated in the urine.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose of 50 mg once daily. May be increased to 50 mg twice daily after 4 weeks if needed. Maximum dose is 100 mg daily.
- Heart Failure Post-MI: Initial dose of 25 mg once daily, titrated to 50 mg once daily within 4 weeks as tolerated.
- Chronic Heart Failure: Initial dose of 25 mg once daily, titrated to 50 mg once daily within 4 weeks as tolerated.
Children: Safety and efficacy in children have not been established.
Special Cases:
- Elderly Patients: Start with the standard adult dose. Careful monitoring for hyperkalemia is recommended.
- Patients with Renal Impairment: Contraindicated in patients with CrCl <30 mL/min. Dose reduction is required for patients with CrCl 30-50 mL/min (start at 25 mg every other day).
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Close monitoring for hyperkalemia in patients with diabetes, concomitant use of ACE inhibitors or ARBs, and NSAIDs.
Clinical Use Cases
Eplerenone is not indicated for the specific clinical settings of intubation, surgical procedures, mechanical ventilation, ICU use, or acute emergency situations (e.g., status epilepticus, cardiac arrest).
Dosage Adjustments:
Adjustments may be necessary based on serum potassium levels, concomitant medications (especially CYP3A4 inhibitors), and renal function.
Side Effects
Common Side Effects:
Hyperkalemia, dizziness, cough, fatigue, abdominal pain, diarrhea, headache.
Rare but Serious Side Effects:
Severe hyperkalemia, gynecomastia, vaginal bleeding (abnormal), angioedema.
Long-Term Effects:
Potential for hyperkalemia with long-term use, especially in patients with renal impairment or concomitant use of potassium-sparing diuretics.
Adverse Drug Reactions (ADR):
Severe hyperkalemia, potentially life-threatening if not promptly addressed.
Contraindications
- Hyperkalemia (serum potassium >5.0 mEq/L).
- Severe renal impairment (CrCl <30 mL/min).
- Severe hepatic impairment (Child-Pugh Class C).
- Concomitant use of potassium-sparing diuretics or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir).
- Type 2 diabetes with microalbuminuria (for hypertension).
Drug Interactions
- CYP3A4 Inhibitors: Increase eplerenone levels. Dose reduction may be necessary.
- Potassium-sparing Diuretics and Potassium Supplements: Increased risk of hyperkalemia. Avoid concomitant use.
- ACE Inhibitors and ARBs: Increased risk of hyperkalemia. Monitor potassium closely.
- NSAIDs: Can reduce renal function and increase risk of hyperkalemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C. Use only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: Excretion in breast milk is unknown. Exercise caution.
Drug Profile Summary
- Mechanism of Action: Selective aldosterone receptor antagonist.
- Side Effects: Hyperkalemia, dizziness, cough, fatigue.
- Contraindications: Hyperkalemia, severe renal/hepatic impairment, concomitant use of potassium-sparing diuretics or strong CYP3A4 inhibitors.
- Drug Interactions: CYP3A4 inhibitors, potassium-sparing diuretics, potassium supplements, ACE inhibitors, ARBs, NSAIDs.
- Pregnancy & Breastfeeding: Category C; unknown if excreted in breast milk.
- Dosage: Hypertension: 50-100 mg daily; Post-MI HF: 25-50 mg daily; Chronic HF: 25-50mg daily
- Monitoring Parameters: Serum potassium, renal function, blood pressure.
Popular Combinations
- Eplerenone + ACE inhibitor/ARB (for HF and hypertension): Synergistic effect in reducing blood pressure and improving HF outcomes. Careful potassium monitoring is crucial.
Precautions
- General Precautions: Monitor serum potassium, renal function, and blood pressure regularly. Assess for drug interactions.
- Specific Populations: As described in the “Dosage” section.
- Lifestyle Considerations: Encourage lifestyle modifications such as diet, exercise, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Eplerenone?
A: For hypertension: 50-100 mg daily. For Post-MI heart failure and chronic heart failure: 25-50 mg daily.
Q2: What is the mechanism of action of Eplerenone?
A: Eplerenone selectively blocks aldosterone binding to the mineralocorticoid receptor.
Q3: What are the common side effects of Eplerenone?
A: Common side effects include hyperkalemia, dizziness, cough, fatigue, and gastrointestinal disturbances.
Q4: What are the contraindications for using Eplerenone?
A: Contraindications include hyperkalemia, severe renal/hepatic impairment, and concomitant use of potassium-sparing diuretics or strong CYP3A4 inhibitors.
Q5: How should I monitor patients on Eplerenone?
A: Monitor serum potassium regularly, especially during initiation and dose titration. Monitor renal function and blood pressure.
Q6: Can Eplerenone be used in patients with hepatic impairment?
A: Yes, no dose adjustment is generally necessary in patients with hepatic impairment.
Q7: Can Eplerenone be used in patients with renal impairment?
A: Eplerenone is contraindicated in severe renal impairment (CrCl <30 mL/min) and requires dose reduction in moderate renal impairment (CrCl 30-50 mL/min).
Q8: Does food affect the absorption of Eplerenone?
A: No, food does not significantly affect the absorption of Eplerenone.
Q9: What is the role of Eplerenone in treating heart failure?
A: Eplerenone improves survival and reduces hospitalization for heart failure in patients post-MI and in those with NYHA class II chronic heart failure.
Q10: How does Eplerenone differ from spironolactone?
A: Both are aldosterone antagonists, but eplerenone is more selective for the mineralocorticoid receptor, resulting in a lower incidence of endocrine-related side effects such as gynecomastia and menstrual irregularities.
