Spironolactone is indicated for the treatment of edema and ascites associated with liver cirrhosis, malignant ascites, nephrotic syndrome, congestive heart failure, and primary hyperaldosteronism.

Description: Spironolactone is an aldosterone antagonist and potassium-sparing diuretic. It acts by competitively binding to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. This results in increased excretion of sodium and water while conserving potassium and magnesium.

Mode of Action: Spironolactone and its active metabolites act as specific antagonists of aldosterone by competitively binding to receptors in the distal renal tubule. This leads to increased sodium and water excretion while potassium is retained. Through this mechanism, it acts both as a diuretic and antihypertensive agent and may be used alone or in combination with other diuretics acting at more proximal sites in the nephron.

Absorption: Peak plasma concentrations of spironolactone and its active metabolite canrenone occur at approximately 2.6 hours and 4.3 hours, respectively, in healthy individuals. Food increases spironolactone bioavailability (AUC) by about 95.4%; therefore, a consistent relationship with meals is recommended.

Distribution: More than 90% of spironolactone and its metabolites are bound to plasma proteins.

Metabolism: Spironolactone undergoes rapid and extensive metabolism. Its metabolites are classified into sulfur-removed forms (e.g., canrenone) and sulfur-retained forms (e.g., TMS and HTMS). In humans, TMS and 7-α-thiospirolactone have approximately one-third the potency of spironolactone in antagonizing fludrocortisone effects on urinary electrolytes.

Elimination & Excretion: The elimination half-life of spironolactone is about 1.4 hours. The metabolites have longer half-lives: canrenone (16.5 hours), TMS (13.8 hours), and HTMS (15 hours). These metabolites are primarily excreted in urine and secondarily in bile.

Heart Failure: Initiate treatment at 25 mg once daily.

Hypertension: Initiate treatment at 25 to 100 mg daily in either single or divided doses.

Essential hypertension: For adults, an initial daily dosage of 50 to 100 mg of Spironolactone administered in either single or divided doses is recommended.

Primary hyperaldosteronism: Spironolactone may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome): An initial daily dosage of 50–100 mg of Spironolactone administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily.

Hypokalemia: Spironolactone in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia, when oral potassium supplements or other potassium-sparing regimens are considered inappropriate.

The use of potassium supplements, potassium-rich diet (including salt substitutes), or other potassium-sparing agents is not recommended, as it may lead to hyperkalemia. Severe hyperkalemia has been reported when Spironolactone is used together with other potassium-sparing diuretics and ACE inhibitors. Spironolactone may reduce vascular responsiveness to noradrenaline; therefore, caution is required during regional or general anesthesia in patients receiving this drug. Aspirin may reduce the diuretic effect of Spironolactone by inhibiting the secretion of canrenone in the renal tubules. Indomethacin and mefenamic acid may also reduce the excretion of canrenone. Carbenoxolone may cause sodium retention and reduce the effectiveness of Spironolactone; therefore, concomitant use should be avoided. Spironolactone may enhance the metabolism of antipyrine.

Acute renal failure, significant renal impairment, anuria, hyperkalemia, or known hypersensitivity to Spironolactone.

Gynecomastia may occur with Spironolactone use. It is dose- and duration-related and is usually reversible after discontinuation, although in rare cases it may persist.

Other reported adverse effects include gastrointestinal symptoms (cramping, diarrhea), drowsiness, lethargy, headache, maculopapular or erythematous rash, urticaria, mental confusion, drug fever, ataxia, impotence, menstrual irregularities, amenorrhea, and postmenopausal bleeding. Most adverse effects are reversible after stopping the drug.

There are risks to both mother and fetus associated with heart failure, cirrhosis, and poorly controlled hypertension during pregnancy. No data are available regarding the effect of spironolactone on milk production.

Patients receiving diuretics should be monitored for fluid and electrolyte imbalance, including hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia. Serum and urine electrolyte monitoring is especially important in patients with vomiting or receiving intravenous fluids. Hyperkalemia may occur in patients with renal impairment or excessive potassium intake and can cause potentially fatal cardiac arrhythmias. Therefore, potassium supplementation is generally not recommended.

Acute overdose of Spironolactone may cause drowsiness, confusion, rash, nausea, vomiting, dizziness, or diarrhea. In rare cases, hyponatremia, hyperkalemia, or hepatic coma may occur, especially in patients with severe liver disease. Hyperkalemia is more likely in patients with renal impairment.

Potassium-sparing diuretics, Aldosterone antagonists

Keep out of reach of children. Store in a dry place below 30°C and protect from light.