Spironolactone

ATC code

C03DA01

Therapeutic class

Potassium-sparing diuretic · Aldosterone antagonist

Forms

oral tablet

Brand names

Aldactone (ES) · Qaialdo (EU) · Aldactone (US)

Overall confidence

high

Regulatory sources consulted

ema-epar-EMEA/H/C/005535
aemps-cima-54900
PubMed PMID:39374998 ↗
PubMed PMID:37993292 ↗
PubMed PMID:41871713 ↗
KDIGO 2024 CKD Guideline
ESC 2021 Heart Failure Guidelines

Approved indications

In the management of refractory oedema associated with congestive cardiac failure; hepatic cirrhosis with ascites and oedema, malignant ascites, nephrotic syndrome, diagnosis and treatment of primary aldosteronism, essential hypertension.
Heart failure with reduced ejection fraction (HFrEF) (NYHA Class II-IV) to reduce morbidity and mortality, in addition to standard therapy.

Contraindications

Absolute

Hyperkalemia (serum potassium > 5.0 mEq/L at treatment initiation).
Severe renal impairment (eGFR < 30 mL/min/1.73m²).
Addison's disease.
Concomitant use with eplerenone or other potassium-sparing diuretics.

Clinical warnings

Major warning · Hyperkalemia: Significant risk of increased serum potassium, which can be fatal. The risk is increased by renal impairment, diabetes, advanced age, and concomitant use of ACE inhibitors, ARBs, NSAIDs, or potassium supplements. — EMA SPC
Hormonal effects: May cause gynecomastia, breast tenderness, menstrual irregularities, and decreased libido due to its antiandrogenic and progestogenic activity. Gynecomastia is usually reversible upon discontinuation. — EMA SPC

Drug interactions

ModerateACE inhibitors (e.g., Ramipril), ARBs (e.g., Losartan)C09AA05
Mechanism: Both reduce aldosterone production/effect, decreasing potassium excretion. Additive risk of hyperkalemia, especially in patients with renal impairment.
Recommendation: Use with extreme caution. Start with low doses of spironolactone and monitor serum potassium frequently (e.g., at 1 week, 1 month, and then periodically).
EMA SPC
ModerateNSAIDs (e.g., Ibuprofen)M01AE01
Mechanism: NSAIDs can reduce the diuretic and antihypertensive effect, and increase the risk of nephrotoxicity and hyperkalemia by inhibiting renal prostaglandin synthesis.
Recommendation: Avoid chronic concomitant use if possible. Monitor blood pressure, renal function, and serum potassium, especially at initiation.
EMA SPC
HighTrimethoprimJ01EA01
Mechanism: Trimethoprim inhibits the epithelial sodium channel (ENaC) in the renal distal tubule, similar to amiloride, causing potassium retention. Very high risk of severe hyperkalemia.
Recommendation: Avoid the combination. If absolutely necessary, requires hospitalization and very close monitoring of serum potassium.
PMID:25475490

Adverse events

Common (≥1%)

hyperkalemia · gynecomastia · breast pain/tenderness · menstrual irregularities · decreased libido · headache · dizziness · nausea · leg cramps

Rare but serious

severe hyperkalemia · agranulocytosis · Stevens-Johnson syndrome (SJS) · toxic epidermal necrolysis (TEN) · acute kidney injury

Pregnancy and lactation

Contraindicated in pregnancy due to its antiandrogenic effects and the potential for feminization of a male fetus. It is excreted in breast milk; a decision should be made whether to discontinue nursing or to discontinue the drug, weighing the benefit to the mother.

Recent literature (PubMed)

Executive summary of the Spanish consensus for the diagnosis, management, and follow-up of primary hyperaldosteronism.
Araujo-Castro M, et al. · Endocrinol Diabetes Nutr (Engl Ed) · 2024 · Relevance 5/5
Resumen ejecutivo de un consenso multidisciplinario español sobre el hiperaldosteronismo primario (HP). Reafirma que el HP es la causa más común de hipertensión secundaria y está infradiagnosticado. Subraya la importancia del diagnóstico precoz y el tratamiento adecuado (incluyendo ARM como espironolactona) para reducir la morbimortalidad cardiometabólica asociada al exceso de aldosterona.
Primary aldosteronism: Practical recommendations for treatment and follow-up.
Araujo-Castro M, et al. · Hipertens Riesgo Vasc · 2023 · Relevance 4/5
Revisión que establece recomendaciones prácticas para el manejo del hiperaldosteronismo primario (HP). Destaca que los antagonistas del receptor mineralocorticoide (ARM), como la espironolactona, son el tratamiento de elección para las formas bilaterales de HP, con el objetivo de revertir los efectos cardiovasculares adversos, normalizar el potasio y la presión arterial.
Health status and effects of spironolactone in people at high risk of heart failure: The Heart OMics in AGEing (HOMAGE) randomized trial.
Aguiar-Neves I, et al. · Rev Port Cardiol · 2026 · Relevance 3/5
Análisis post-hoc del ensayo HOMAGE que evaluó el efecto de la espironolactona sobre la calidad de vida en personas con riesgo de desarrollar insuficiencia cardíaca. El estudio encontró que la espironolactona no influyó en el estado de salud o la calidad de vida durante un seguimiento de 9 meses en esta población de prevención primaria.