Summary about Spironolactone
Spironolactone is a potassium sparing diuretic like that competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention. Spironolactone was originally developed purely for this ability before other pharmacodynamic properties of the drug were discovered. It is indicated to treat a number of conditions including heart failure, deem, hyperaldosteronism, adrenal hyperplasia, hypertension, and nephrotic syndrome. Off label uses of spironolactone involving its antiandrogenic activity include hirsutism, female pattern hair loss, and adult acne vulgaris. Spironolactone is also frequently used in medical gender transition.
|Spironolactone and alcohol may have additive effects in lowering your blood pressure. Patients may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. These side effects are most likely to be seen at the beginning of treatment, following a dose increase, or when treatment is restarted after an interruption.|
|25, 50 ,100 mg|
|A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
Excreted into human milk: Yes (as active metabolite)According to some authorities, use of this drug appears acceptable during breastfeeding.
Originally spironolactone was only studied for its potassium sparing diuretic effect. Spironolactone competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention. Inhibition of this receptor leads to increased renin and aldosterone levels.
Spironolactone is structurally similar to progesterone and as a result is associated with progestogenic and antiandrogenic effects.
Duration: Tablet: 2 to 3 days
Bioavailability: High-fat/-calorie meal increased the bioavailability of spironolactone ~90%.
Protein binding: >90%
Metabolism: Rapid and extensive; hepatic to multiple metabolites, including active metabolites canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alpha
Half-life elimination: 1.4 hours;
Time to peak, serum: 2.6 to 4.3 hours (primarily as active metabolites)
Excretion: Urine (primarily as metabolites) and bile (secondary)
|25 mg (per each): $0.19 – $0.46 |
50 mg (per each): $0.81 – $0.88
100 mg (per each): $1.42
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|Tablets of 25, 50 and 100 mg|
|Severe (NYHA class III to IV): Oral: Initial: 12.5 to 25 mg once daily; maximum: 50 mg/day. If 25 mg once daily not tolerated, may reduce to 25 mg every other day |
NYHA class II; LVEF ≤35% (off-label use): Oral: 12.5 to 25 mg once daily; maximum: 50 mg/day
Post myocardial infarction; LVEF ≤40% (off-label use): Oral: 12.5 to 25 mg once daily; maximum: 50 mg/day .
Note: Withhold treatment if potassium >5.5 mEq/L or renal function worsens; hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours.
Suspension: Serum potassium ≤5 mEq/L: Initial: 20 mg once daily. May titrate to 37.5 mg once daily or decrease to 20 mg every other day as clinically indicated.
Hypertension (alternative agent): Oral: Initial:
Tablet: 25 to 50 mg daily in 1 or 2 divided doses; may titrate every 2 weeks as needed based on patient response up to 100 mg daily
Suspension: 20 to 100 mg daily in 1 or 2 divided doses; may titrate at 2-week intervals Note: Doses >75 mg/day generally do not provide additional reductions in blood pressure.
Primary aldosteronism: Oral: Tablet:
Maintenance until surgical correction: 100 to 400 mg once daily.
Treatment of bilateral adrenal hypersecretion, or unilateral hypersecretion in patients unwilling or unable to undergo surgery: Initial: 12.5 to 25 mg once daily; gradually titrate upward if necessary to the lowest effective dose (maximum: 100 mg/day)
Acne vulgaris (females) (off-label use): Oral: 50 to 200 mg once daily
Ascites, due to cirrhosis (off-label dose): Initial: 100 mg once daily; titrate every 3 to 5 days as clinically indicated (usual maximum: 400 mg once daily); a spironolactone to furosemide dosing ratio of 100 mg (spironolactone) to 40 mg (furosemide) should be maintained
Hirsutism (off-label use): Females: Oral: Usual therapeutic dose: 100 to 200 mg/day in 2 divided doses; assess response at 6-month intervals before adjusting dose, adding additional agents, or switching to alternative therapy
Hormone therapy for transgender females (male-to-female) (adjunct) (off-label use): Oral: Initial: 25 mg twice daily in combination with other appropriate agents; increase each week based on response and tolerability to a usual dose of 100 to 300 mg/day. Adjust dose with a goal of suppressing serum testosterone levels into the normal range for females (ie, <50 ng/dL). Maximum: 200 mg twice daily
|C03DA — Aldosterone antagonists|
|Food increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.|
|100% of Medicare Part D and Medicare Advantage plans cover this drug.|
|ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia. |
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Pressor amines (e.g., norepinephrine): Spironolactone reduces the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with spironolactone.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxant may result.
Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Nonsteroidal anti-inflammatory drugs (NSAIDs): In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing and thiazide diuretics.
Combination of NSAIDs, e.g., indomethacin, with potassium-sparing diuretics has been associated with severe hyperkalemia. Therefore, when spironolactone and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Digoxin: Spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and digitalization doses when spironolactone is administered, and the patient should be carefully monitored to avoid over or underdigitalization.
Is Available Generically
Is not subject to the Controlled Substances Act.
Mechanism of Action
|Spironolactone competitively inhibits aldosterone dependant sodium potassium exchange channels in the distal convoluted tubule This action leads to increased sodium and water excretion, but more potassium retention. The increased excretion of water leads to diuretic and also antihypertensive effects.|
Non Proprietary Name
|Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Rarely, instances of hyponatremia, hyperkalemia, or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage. Hyperkalemia may occur, especially in patients with impaired renal function.|
|Use is considered contraindicated; use during pregnancy requires the benefit be weighed against the risk to the fetus. |
AU TGA pregnancy category: B3
US FDA pregnancy category: CAU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
|Use is considered contraindicated; use during pregnancy requires the benefit be weighed against the risk to the fetus. |
Comments: Adequate methods of contraception should be encouraged.
Animal studies have revealed an increased resorption rate, decreased live fetuses, and progestational and antiandrogenic effects. There are no controlled data in human pregnancy.
|Eplerenone, Canrenone, Canerenoic acid|
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance, e.g., hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal. Consequently, no potassium supplement should ordinarily be given with Spironolactone. Concomitant administration of potassium-sparing diuretics and ACE inhibitors or nonsteroidal antiinflammatory drugs (NSAIDs), e.g., indomethacin, has been associated with severe hyperkalemia. If hyperkalemia is suspected (warning signs include paresthesia, muscle weakness, fatigue, flaccid paralysis of the extremities, bradycardia and shock), an electrocardiogram. (ECG) should be obtained. However, it is important to monitor serum potassium levels because mild hyperkalemia may not be associated with ECG changes. If hyperkalemia is present, Spironolactone should be discontinued immediately. With severe hyperkalemia, the clinical situation dictates the procedures to be employed. These include the intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. These are temporary measures to be repeated as required. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.
Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.
Dilutional hyponatremia, manifested by dryness of the mouth, thirst, lethargy, and drowsiness, and confirmed by a low serum sodium level, may be caused or aggravated, especially when Spironolactone is administered in combination with other diuretics, and dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of sodium, except in rare instances when the hyponatremia is life-threatening.
Spironolactone therapy may cause a transient elevation of BUN, especially in patients with preexisting renal impairment. Spironolactone may cause mild acidosis.
Gynecomastia may develop in association with the use of Spironolactone; physicians should be alert to its possible onset. The development of gynecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when Spironolactone is discontinued. In rare instances some breast enlargement may persist when Spironolactone is discontinued.
Drugs.com [Internet]. Spironolactone Information from Drugs.com; c1996-2019 [Updated: 9 December 2018, Cited: 7 December 2019]. Available from: https://www.drugs.com/spironolactone.html
Drugbank.ca [Internet]. Spironolactone Information from Drugbank.ca; c1996-2019 [Updated: 6 December 2019, Cited: 7 December 2019]. Available from: https://www.drugbank.ca/drugs/DB00421
Uptodate.com [Internet]. Spironolactone Information from Uptodate.com; c1996-2019 [Topic 9621 Version 383.0, Cited: 7 December 2019]. Available from https://www.uptodate.com/contents/spironolactone-drug-information#F222856