INSPRA

What it is

INSPRA contains eplerenone. Eplerenone is supplied as film-coated tablets containing 25 or 50 mg eplerenone. Eplerenone is a relatively selective mineralocorticoid receptor antagonist with weak binding to androgen, glucocorticoid and progesterone receptors. Eplerenone prevents the binding of aldosterone, a key hormone in the renin-angiotensin-aldosterone-system (RAAS), which is involved in the regulation of blood pressure and the pathophysiology of cardiovascular disease.

Approved indications

— To reduce the risk of cardiovascular death in combination with standard therapy in patients who have evidence of heart failure and left ventricular impairment within 3-14 days of an acute myocardial infarction. — To reduce the risk of cardiovascular mortality and morbidity in adult patients with NYHA Class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30% or LVEF ≤35% in addition to QRS duration of > 130 msec), in addition to standard optimal therapy.

Dosing overview

For post-myocardial infarction heart failure: Treatment should be initiated at 25 mg once daily and titrated to the target dose of 50 mg once daily within 4 weeks as tolerated by the patient. For NYHA Class II chronic heart failure in patients with eGFR ≥50 mL/min/1.73 m²: Treatment should be initiated at a dose of 25 mg once daily and titrated to the target dose of 50 mg once daily preferably within 4 weeks; taking into account the serum potassium levels. Serum potassium should be measured before initiating eplerenone therapy, within the first week and at 1-month after the start of treatment or dosage adjustment, and serum potassium should be assessed periodically thereafter, with the dose of eplerenone adjusted based on the serum potassium level. In case of concomitant treatment with mild to moderate CYP3A4 inhibitors (such as amiodarone, diltiazem, erythromycin, saquinavir, fluconazole and verapamil), dosing should not exceed 25 mg once daily.

Key safety warnings

The principal risk of eplerenone is hyperkalaemia. Hyperkalaemia can cause serious, sometimes fatal, arrhythmias. Hyperkalaemia can be minimized by patient selection, avoidance of certain concomitant treatments, and periodic monitoring until the effect of eplerenone has been established. Eplerenone should generally not be administered to patients taking potassium supplements, or salt substitutes containing potassium. The risk of hyperkalaemia may increase when eplerenone is used in combination with an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) and therefore this combination is not recommended. Diabetic patients with CHF post-MI, including those with proteinuria, should also be treated with caution. The subset of patients in EPHESUS with both diabetes and proteinuria on the baseline urinalysis had increased rates of hyperkalaemia. The risk of hyperkalaemia increases with declining renal function. Due to age-related decreases in creatinine clearance, the incidence of laboratory-documented hyperkalaemia was increased in patients 65 and older.

Contraindications

INSPRA is contraindicated in patients with hypersensitivity to eplerenone or any of the excipients. Eplerenone should not be administered to patients with clinically significant hyperkalaemia (serum potassium >5.0 mmol/L at initiation). Eplerenone should not be administered to patients with severe renal insufficiency (eGFR <30 mL per minute per 1.73 m², CKD stages 4 and 5). Eplerenone should not be administered to patients with severe hepatic insufficiency. Eplerenone should not be co-administered to patients receiving potassium-sparing diuretics or strong inhibitors of CYP3A4 (such as itraconazole, ketoconazole, ritonavir and clarithromycin).

PBS listing

No PBS listing information has been provided in the source documents.

Regulatory history

INSPRA eplerenone was first listed on the ARTG on 22 June 2005 for both 25 mg and 50 mg tablet formulations. An Australian Public Assessment Report (AusPAR) was approved on 23 May 2013, extending the indications for INSPRA to allow use for reducing the risk of cardiovascular death in patients with heart failure and left ventricular impairment post-acute myocardial infarction, and to reduce cardiovascular mortality and morbidity in adult patients with NYHA Class II chronic heart failure and left ventricular systolic dysfunction. In December 2025, the PBAC recommended amendments to align with contemporary clinical guidelines for the management of heart failure, noting improved efficacy and safety profile over spironolactone.