ALDACTONE

What it is

ALDACTONE is spironolactone, available in 25 mg and 100 mg tablet strengths. Spironolactone is a specific pharmacological antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium-potassium exchange site in the distal convoluted renal tubule. It causes increased amounts of sodium and water to be excreted, while potassium is retained, and has both diuretic and antihypertensive activity.

Approved indications

— Essential hypertension. — Adjunctive therapy in malignant hypertension. — Diuretic-induced hypokalaemia when other measures are considered inappropriate or inadequate. — Prophylaxis of hypokalaemia in patients taking digitalis when other measures are considered inadequate or inappropriate. — Congestive cardiac failure. — Hepatic cirrhosis with ascites and oedema. — Nephrotic syndrome. — Diagnosis and treatment of primary hyperaldosteronism. — Hirsutism in females.

Dosing overview

For essential hypertension in adults, the dose is 50 to 100 mg per day, which may be given either in divided doses or as a single daily dose. Dosage should be adjusted according to response, but maximum effect may not occur for up to two weeks after starting treatment. For oedematous disorders, dosing varies by condition:

For female hirsutism, 100 to 200 mg per day in divided doses is usual, although 50 mg daily has also been shown to be effective, with clinical improvement usually shown within 3 to 6 months.

Key safety warnings

Concomitant use of spironolactone with angiotensin converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs, angiotensin II antagonists, aldosterone blockers, heparin, low molecular weight heparin, other drugs or conditions known to cause hyperkalaemia or potassium supplements, a diet rich in potassium including salt substitutes containing potassium, or other potassium sparing agents is not recommended as it may lead to severe hyperkalaemia. Hyperkalaemia may be fatal in patients with severe heart failure (New York Heart Association Class III–IV). Potassium and creatinine levels should be closely monitored one week after initiation or monthly for the first 3 months, then quarterly for a year, and then every 6 months when increasing the dose of spironolactone. Gynacomastia may develop in association with the use of spironolactone; the development appears to be related to both dosage level and duration of therapy and is normally reversible when spironolactone is discontinued. Spironolactone has been shown to increase the half-life of digoxin, which may result in increased serum digoxin levels and subsequent digitalis toxicity; it may be necessary to reduce the digoxin dose when spironolactone is administered.

Contraindications

Acute renal insufficiency, significant impairment of renal function, anuria, Addison's disease or other conditions associated with hyperkalaemia, hyperkalaemia, pregnancy, hypersensitivity to spironolactone, and concomitant use of eplerenone are contraindications.

Regulatory history

ALDACTONE was first listed on the Australian Register of Therapeutic Goods on 28 May 1999, with both the 25 mg and 100 mg tablet strengths registered (ARTG 68953 and ARTG 68954 respectively).