spironolactone
Aldactone

Available forms
Available by prescription only
Tablets: 25 mg
Tablets (film-coated): 25 mg, 50 mg, 100 mg

Indications and dosages
 Edema. Adults: 25 to 200 mg P.O. daily in divided doses.
Children: Initially, 3.3 mg/kg or 60 mg/m² P.O. daily in divided doses.
 Hypertension. Adults: 50 to 100 mg P.O. daily in divided doses.
Children: 1 to 2 mg/kg P.O. b.i.d. has been used.
 Diuretic-induced hypokalemia. Adults: 25 to 100 mg P.O. daily when oral potassium supplements are considered inappropriate.
 Detection of primary hyperaldosteronism. Adults: 400 mg P.O. daily for 4 days (short test) or for 3 to 4 weeks (long test). If hypokalemia and hypertension are corrected, a presumptive diagnosis of primary hyperaldosteronism is made.
 Hirsutism ◇. Adults: 50 to 200 mg P.O. daily.
 Premenstrual syndrome ◇. Adults: 25 mg q.i.d. P.O. on day 14 of menstrual cycle.
 Heart failure in patients receiving an ACE inhibitor and a loop diuretic with or without a cardiac glycoside ◇. Adults: Initially, 12.5 to 25 mg P.O. daily.
 To decrease risk of metrorrhagia ◇. Adults: 50 mg b.i.d. P.O. on days 4 through 21 of menstrual cycle.
 Acne vulgaris ◇. Adults: 100 mg P.O. daily.

Pharmacodynamics
Diuretic and potassium-sparing actions: Spironolactone competitively inhibits aldosterone effects on the distal renal tubules, increasing sodium and water excretion and decreasing potassium excretion.
 Spironolactone is used to treat edema associated with excessive aldosterone secretion, such as that associated with hepatic cirrhosis, nephrotic syndrome, and heart failure. It’s also used to treat diuretic-induced hypokalemia.
Antihypertensive action: The mechanism of action is unknown. Spironolactone may block the effect of aldosterone on arteriolar smooth muscle.
Diagnosis of primary hyperaldosteronism: Spironolactone inhibits the effects of aldosterone; therefore, correction of hypokalemia and hypertension is presumptive evidence of primary hyperaldosteronism.

Pharmacokinetics
Absorption: About 90% is absorbed after oral administration.
Distribution: Drug and its major metabolite, canrenone, are more than 90% plasma protein-bound.
Metabolism: Rapidly and extensively metabolized to canrenone.
Excretion: Canrenone and other metabolites are excreted primarily in urine, and a small amount is excreted in feces via the biliary tract; half-life of canrenone is 13 to 24 hours. Half-life of parent compound is 1 to 2 hours.

Contraindications and precautions
Contraindicated in patients with anuria, acute or progressive renal insufficiency, or hyperkalemia and in those receiving amiloride or triamterene. Use cautiously in patients with impaired renal function, hepatic disease, or fluid and electrolyte imbalances.

Interactions
Drug-drug. ACE inhibitors, potassium supplements, potassium-containing drugs such as parenteral penicillin G: Increases risk of hyperkalemia when administered with these drugs. Use together cautiously, especially in patients with renal impairment.
Anesthetics, norepinephrine: Reduces response to these drugs. Use together cautiously.
Antihypertensives: May potentiate hypotensive effects. May be used to therapeutic advantage.
Aspirin: May slightly decrease response to spironolactone. Watch for diminished effect.
Cardiac glycosides: Increases serum digoxin levels and subsequent toxicity. Monitor digoxin levels.
NSAIDs, such as ibuprofen or indomethacin: May impair renal function, thus affecting potassium excretion. Avoid use together.
Potassium-sparing diuretics: Increases risk of hyperkalemia. Avoid use together.
Drug-herb. Licorice: May block antiulcer and aldosterone-like effects of herb. Discourage use together.
Drug-food. Potassium-containing salt substitutes, potassium-rich foods (such as citrus fruit and tomatoes): Increases risk of hyperkalemia. Advise caution.

Adverse reactions
CNS: headache, drowsiness, lethargy, confusion, ataxia.
GI: diarrhea, gastric bleeding, ulceration, cramping, gastritis, vomiting.
GU: inability to maintain erection, menstrual disturbances in women.
Hematologic: agranulocytosis.
Metabolic: hyperkalemia, dehydration, hyponatremia, metabolic acidosis.
Skin: hirsutism, urticaria, maculopapular eruptions.
Other: gynecomastia, breast soreness in women, drug fever.

Effects on lab test results
• May increase BUN and potassium levels. May decrease sodium level.
• May decrease granulocyte count.

Overdose and treatment
Signs and symptoms of overdose are consistent with dehydration and electrolyte disturbance.
 Treatment is supportive and symptomatic. In acute ingestion, empty stomach by emesis or lavage. In severe hyperkalemia (more than 6.5 mEq/L), reduce serum potassium levels with I.V. sodium bicarbonate or glucose with insulin. A cation exchange resin, sodium polystyrene sulfonate (Kayexalate), given orally or as a retention enema, may also reduce serum potassium levels.

Special considerations
• Give drug with meals to enhance absorption.
• Protect drug from light.
• Spironolactone is antiandrogenic and has been used to treat hirsutism in doses of 200 mg/day.
• Avoid unnecessary use of drug. Drug has been shown to induce tumors in laboratory animals.
• Diuretic effect may be delayed 2 to 3 days if drug is used alone; maximum antihypertensive effect may be delayed 2 to 3 weeks.
• Adverse reactions are related to dose levels and duration of therapy and usually disappear with withdrawal of drug; however, gynecomastia may persist.
• Watch for hyperchloremic metabolic acidosis.
Breast-feeding patients
• Safety during breast-feeding hasn’t been established. Canrenone, a metabolite, appears in breast milk. Recommend an alternative to breast-feeding during spironolactone therapy.
Pediatric patients
• When giving drug to children, crush tablets and mix in cherry syrup as an oral suspension.
Geriatric patients
• These patients are more susceptible to diuretic effects and may need lower doses to prevent excessive diuresis.

Patient education
• Instruct patient to report mental confusion or lethargy immediately.
• Explain that adverse reactions usually disappear after drug is discontinued; gynecomastia, however, may persist.
• Caution patient to avoid hazardous activities such as driving until response to drug is known.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use