pharmacopeia
GET
/api/v1/drug/spironolactone
2D structure
S-[(7R,8R,9S,10R,13S,14S,17R)-10,13-dimethyl-3,5'-dioxospiro[2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-yl] ethanethioate
SMILES CC(=O)S[C@@H]1CC2=CC(=O)CC[C@@]2([C@@H]3[C@@H]1[C@@H]4CC[C@]5([C@]4(CC3)C)CCC(=O)O5)C
InChIKey LXMSZDCAJNLERA-ZHYRCANASA-N

Mechanism of action

Sourced from openFDA

Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained.

Aldosterone

Indications

Sourced from openFDA
  • Spironolactone is an aldosterone antagonist indicated for: The treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and to reduce the need for hospitalization for heart failure ( 1.1 ). Use as an add-on therapy for the treatment of hypertension, to lower blood pressure.ICD-10: I10, I50.9, R60.9

Contraindications

Sourced from openFDA
  • Spironolactone is contraindicated in the patients with: Hyperkalemia Addison’s disease Concomitant use of eplerenone Spironolactone is contraindicated in patients with ( 4 ): Hyperkalemia Addison’s disease Concomitant use of eplerenonecontraindicated

Dosage & administration

Sourced from openFDA

Heart Failure: Initiate treatment at 25 mg once daily ( 2.2 ). Hypertension: Initiate treatment at 25 to 100 mg daily in either single or divided doses ( 2.3 ). Edema: Initiate therapy in a hospital setting and titrate slowly. The recommended initial daily dose is 100 mg in single or divided doses ( 2.4 ). Primary hyperaldosteronism: Initiate treatment at 100 to 400 mg in preparation for surgery. In patients unsuitable for surgery use the lowest effective dosage determined for the individual patient ( 2.5 ). 2.1 General Considerations Spironolactone can be taken with or without food, but should be taken consistently with respect to food [see Clinical Pharmacology (12.3) ] . 2.2 Treatment of Heart Failure In patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m², initiate treatment at 25 mg once daily. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who develop hyperkalemia on 25 mg once daily may have their dosage reduced to 25 mg every other day [see Warnings and Precautions (5.1) ] . In patients with an eGFR between 30 and 50 mL/min/1.73 m 2 , consider initiating therapy at 25 mg every other day because of the risk of hyperkalemia [see Use in Specific Populations (8.6) ]. 2.3 Treatment of Essential Hypertension The recommended initial daily dose is 25 to 100 mg of spironolactone administered in either single or divided doses is recommended. Dosage can be titrated at two-week intervals. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure.

Warnings & precautions

Sourced from openFDA

Hyperkalemia: Monitor serum potassium within one week of initiation and regularly thereafter ( 5.1 ). Hypotension and Worsening Renal Function: Monitor volume status and renal function periodically ( 5.2 ). Electrolyte and Metabolic Abnormalities: Monitor serum electrolytes, uric acid and blood glucose periodically ( 5.3 ). Gynecomastia: Spironolactone can cause gynecomastia ( 5.4 ). 5.1 Hyperkalemia Spironolactone can cause hyperkalemia. This risk is increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers [see Drug Interactions (7.1) ] . Monitor serum potassium within 1 week of initiation or titration of spironolactone and regularly thereafter. More frequent monitoring may be needed when spironolactone is given with other drugs that cause hyperkalemia or in patients with impaired renal function. If hyperkalemia occurs, decrease the dose or discontinue spironolactone and treat hyperkalemia. 5.2 Hypotension and Worsening Renal Function Excessive diuresis may cause symptomatic dehydration, hypotension and worsening renal function, particularly in salt-depleted patients or those taking angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Worsening of renal function can also occur with concomitant use of nephrotoxic drugs (e.g., aminoglycosides, cisplatin, and NSAIDs). Monitor volume status and renal function periodically.

Adverse reactions

Sourced from openFDA

The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperkalemia [see Warnings and Precautions (5.1) ] Hypotension and Worsening Renal Function [see Warnings and Precautions (5.2) ] Electrolyte and Metabolic Abnormalities [see Warnings and Precautions (5.3) ] Gynecomastia [see Warnings and Precautions (5.4) ] Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites [see Use in Specific Populations (8.7) ] The following adverse reactions associated with the use of spironolactone were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure. Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Reproductive: Decreased libido, inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast and nipple pain. Hematologic: Leukopenia (including agranulocytosis), thrombocytopenia. Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis. Metabolism: Hyperkalemia, electrolyte disturbances [see Warnings and Precautions (5.1 , 5.3) ] , hyponatremia, hypovolemia. Musculoskeletal : Leg cramps. Nervous system/psychiatric: Lethargy, mental confusion, ataxia, dizziness, headache, drowsiness.

Use in specific populations

Sourced from openFDA

Pregnancy: Based on animal data, spironolactone may affect sex differentiation of the male during embryogenesis ( 8.1 ). 8.1 Pregnancy Risk Summary Based on mechanism of action and findings in animal studies, spironolactone may affect sex differentiation of the male during embryogenesis [see Data ] . Rat embryofetal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. Limited available data from published case reports and case series did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone . There are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy [see Clinical Considerations ] . Because of the potential risk to the male fetus due to anti-androgenic properties of spironolactone and animal data, avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption The mean time to reach peak plasma concentration of spironolactone and the active metabolite, canrenone, in healthy volunteers is 2.6 and 4.3 hours, respectively. Effect of food : Food increased the bioavailability of spironolactone (as measured by AUC) by approximately 95.4%.

Overdosage

Sourced from openFDA

The oral LD 50 of spironolactone is greater than 1000 mg/kg in mice, rats, and rabbits. 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. Treatment: Induce vomiting or evacuate the stomach by lavage. There is no specific antidote. Treatment is supportive to maintain hydration, electrolyte balance, and vital functions. Patients who have renal impairment may develop hyperkalemia. In such cases, discontinue spironolactone.

Approval history

Sourced from openFDA
  • Jan 21, 1960NDANDA012151Pfizer
  • Jan 27, 1961NDANDA012616Pfizer
  • Aug 3, 1979ANDAANDA086513Mylan
  • Jul 23, 1986ANDAANDA089424Sun Pharm Industries
  • Jul 2, 1987ANDAANDA089534Sun Pharm Industries
  • Aug 20, 2001ANDAANDA040424Mylan
  • Aug 29, 2006ANDAANDA040750Oxford Pharms
  • Aug 4, 2017NDANDA209478Cmp Dev Llc

FDA shortages

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Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

  • Aldactone, Tablet, 100 mg (NDC 0025-1031-31)To be discontinued
    Sponsor: Pfizer Inc.
    Updated
  • Aldactone, Tablet, 25 mg (NDC 0025-1001-31)To be discontinued
    Sponsor: Pfizer Inc.
    Updated

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
137,401 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Dyspnoea10,6887.8%
  2. 2Fatigue8,4276.1%
  3. 3Nausea8,0495.9%
  4. 4Diarrhoea7,6435.6%
  5. 5Acute Kidney Injury6,9065.0%
  6. 6Dizziness6,4204.7%
  7. 7Headache6,0784.4%
  8. 8Hypotension5,9304.3%
  9. 9Off Label Use5,7994.2%
  10. 10Drug Ineffective5,3323.9%
  11. 11Fall5,1973.8%
  12. 12Asthenia5,1093.7%
  13. 13Death5,0253.7%
  14. 14Hyperkalaemia4,9883.6%
  15. 15Vomiting4,9773.6%

Literature

View JSON

Recent PubMed references pinned to Spironolactone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 323 ClinicalTrials.gov registrations naming Spironolactone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Spironolactone. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

  • ADD1CPIC D (provisional)ClinPGx 3

Structural analogs

View JSON

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

Frequently asked questions

How does Spironolactone work?
Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained.
What is Spironolactone used for?
According to FDA labeling, Spironolactone carries indications including: Spironolactone is an aldosterone antagonist indicated for: The treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and to reduce the need for hospitalization for heart failure ( 1.1 ). Use as an add-on therapy for the treatment of hypertension, to lower blood pressure.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Spironolactone?
Spironolactone is classified as Aldosterone antagonists, Aldosterone Antagonist, Aldosterone Antagonists, Arterial Vasodilation, Decreased Blood Pressure, Decreased Distal Tubule H+ Excretion, Decreased Distal Tubule K+ Excretion, Increased Distal Tubule Na+ Excretion.
What are the brand names for Spironolactone?
Spironolactone is marketed under brand names including Aldactazide, Aldactone, Cardalis, Carospir.
What are the contraindications for Spironolactone?
Spironolactone labeling lists contraindications including: Spironolactone is contraindicated in the patients with: Hyperkalemia Addison’s disease Concomitant use of eplerenone Spironolactone is contraindicated in patients with ( 4 ): Hyperkalemia Addison’s disease Concomitant use of eplerenone. Always consult the full prescribing information and a clinician.
Note. Data for spironolactone is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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