Eplerenone

What it is and how it works

Mechanism of Action Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.

Mechanism class: Aldosterone Antagonists

Indications

Eplerenone tablets are an aldosterone antagonist indicated for: • Improving survival of stable patients with symptomatic heart failure with reduced ejection fraction (HFrEF) after an acute myocardial infarction. • The treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Heart Failure Post-Myocardial Infarction Eplerenone tablets are indicated to improve survival of stable patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI). Hypertension Eplerenone tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and MI. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes.

Dosage and administration (summary)

HFrEF Post-MI: Initiate treatment with 25 mg once daily. Titrate to maximum of 50 mg once daily within 4 weeks, as tolerated. Dose adjustments may be required based on potassium levels. Hypertension: 50 mg once daily, alone or combined with other antihypertensive agents. For inadequate response, increase to 50 mg twice daily. Higher dosages are not recommended. For all patients: Measure serum potassium before starting eplerenone tablets and periodically thereafter. Heart Failure Post-Myocardial Infarction Initiate treatment at 25 mg once daily and titrate to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient.

Contraindications

For All Patients Eplerenone tablets are contraindicated in all patients with: • serum potassium >5.5 mEq/L at initiation, • creatinine clearance ≤30 mL/min, or • concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir) .

Warnings and precautions

• Hyperkalemia: Patients with decreased renal function, diabetes, proteinuria or patients who are taking ACEs and ARBs, NSAIDs or moderate CYP3A inhibitors are at increased risk. Monitor serum potassium levels and adjust dose as needed. Hyperkalemia The risk of hyperkalemia is higher in patients with impaired renal function, proteinuria, diabetes and those concomitantly treated with ACEs, ARBs, NSAIDs and moderate CYP3A inhibitors. Minimize the risk of hyperkalemia with proper patient selection and monitoring .

Pregnancy

Pregnancy Risk Summary The available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes (see Clinical Considerations) .

Storage and supply

Eplerenone Tablets 25 mg are light yellow, round, biconvex, film coated tablets debossed with "V" on one side and "68" on the other side. Bottle of 30 NDC 31722-049-30 Bottle of 90 NDC 31722-049-90 Eplerenone Tablets 50 mg are light yellow, round, biconvex, film coated tablets debossed with "V" on one side and "67" on the other side.

Source: Eplerenone (Eplerenone) — US FDA prescribing information, 2023-06-15, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.