Spironolactone is a "potassium-sparing" diuretic used to treat fluid retention and heart failure, and also to control blood pressure. As the name suggests, it helps the body retain potassium, so your potassium level needs to be checked with blood tests.
Also known as: Aldactone
Severe hyperkalaemia. Combining an ACE inhibitor (Enalapril) with a potassium-sparing diuretic (Spironolactone) significantly increases the risk of hyperkalaemia, especially in patients with renal impairment, diabetes or potassium supplements.
Enalapril reduces aldosterone production and spironolactone blocks the aldosterone receptor in the distal tubule: the combined effect is a marked reduction in potassium excretion. Hyperkalaemia is more frequent in patients with renal impairment, diabetes, advanced age or taking potassium supplements, and may present with muscle weakness, paraesthesias and arrhythmias. The combination is valid and common in heart failure with reduced ejection fraction, where benefit is proven — what is required is surveillance: potassium and creatinine about 1 week after starting or adjusting the dose, and reassessment if renal function worsens.
ACE inhibitor + aldosterone antagonist: additive potassium retention, with risk of hyperkalaemia, especially with reduced GFR, diabetes or advanced age. Monitor potassium and creatinine about 1 week after starting or adjusting.
Enalapril lowers aldosterone (less K+ excretion), an effect amplified by Spironolactone, which directly blocks the aldosterone receptor — serum K+ rises through two pathways.
Serum K+ and creatinine in week 1, then every 4–6 weeks for the first 3 months.
Muscle weakness, paraesthesia, arrhythmias, tall T waves on ECG.
Check serum K+ one week after starting. Consider dose reduction or therapeutic alternatives. Educate the patient on hyperkalaemia symptoms.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73564b3d-8ede-4008-b75c-1277153b5bb6
ARB with a potassium-sparing diuretic raises hyperkalaemia risk.
Both valsartan (ARB) and spironolactone (aldosterone antagonist) reduce renal potassium excretion through complementary pathways — valsartan decreases aldosterone by blocking the AT1 receptor, and spironolactone blocks the mineralocorticoid receptor at the effector end. The spironolactone label classifies "ARBs" among the "agents that increase serum potassium" and recommends "checking serum potassium levels when ACE inhibitor or ARB therapy is altered in patients receiving spironolactone"; the valsartan label warns that "potassium-sparing diuretics, potassium supplements or salt substitutes may lead to increases in serum potassium". The combination is used in HF (RALES demonstrated benefit) but requires rigorous monitoring. Contraindicated if K+ > 5,0 mEq/L or creatinine clearance < 30 mL/min; stop potassium supplements; monitor K+ and creatinine at 3–7 days and 1 month, then quarterly.
Valsartan + spironolactone: additive hyperkalaemia (ARB + K-sparing diuretic). Monitor potassium and renal function; avoid in CKD or K+ > 5,0.
Both spare potassium; risk rises with reduced renal function.
Potassium, heart rhythm.
Hyperkalaemia or arrhythmia.
Monitor potassium; avoid in advanced renal failure.
DailyMed (FDA) — approved Valsartan label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a8af3d9-4053-4233-82a7-e8c7bc9e302f ; approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57d1c333-c229-54aa-e063-6394a90a84ce — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Loop plus potassium-sparing diuretic: risk of electrolyte imbalance.
Spironolactone (potassium-sparing diuretic) and bumetanide (loop diuretic, which excretes potassium) are often used together in heart failure to balance potassium — bumetanide removes K+ and spironolactone retains it. The spironolactone label states that "concomitant administration may lead to hyperkalaemia" and classifies potassium-depleting diuretics as an interaction to monitor; the bumetanide label was not individually analysed, but the net effect depends on renal function and relative doses. In patients with creatinine clearance > 50 mL/min, the balance is generally favourable; in CKD (clearance < 30 mL/min), the risk of hyperkalaemia increases. Monitor potassium and creatinine before initiation and 1 week after; adjust doses according to potassium (if K+ < 3,5 increase spironolactone or reduce bumetanide; if K+ > 5,0 reduce spironolactone or increase bumetanide).
Spironolactone + bumetanide: combination used to regulate potassium in HF (loop loses K, spironolactone spares). Balance depends on renal function; monitor K+.
Used together to manage potassium; balance depends on renal function.
Potassium, creatinine, diuresis.
Cramps, arrhythmia or hypotension.
Monitor electrolytes; avoid in advanced renal failure.
DailyMed (FDA) — approved Bumetanide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4a9229c8-89ba-423e-8e36-f56bc329ed38 ; approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57d1c333-c229-54aa-e063-6394a90a84ce — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
No clinically relevant interaction. The combination is sometimes used intentionally for synergistic diuresis with less hypokalaemia.
Spironolactone (potassium-sparing diuretic) and hydrochlorothiazide (thiazide) have complementary mechanisms in the renal tubule: the thiazide increases sodium and potassium excretion, while spironolactone antagonises aldosterone and retains potassium. The combination is sometimes used intentionally to potentiate diuresis and natriuresis with less hypokalaemia than the thiazide alone. There is no clinically relevant adverse interaction, but the electrolyte balance must be monitored: the main risks are hyperkalaemia in patients with renal impairment or potassium supplements, and hyponatraemia in the elderly.
No clinically relevant interaction. The combination is sometimes used intentionally for synergistic diuresis with less hypokalaemia.
DailyMed/FDA (NIH/NLM) — approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73564b3d-8ede-4008-b75c-1277153b5bb6 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565
ACE inhibitor + spironolactone: serious risk of hyperkalaemia.
Both reduce renal potassium excretion. The combination can cause severe and potentially fatal hyperkalaemia. Monitor K+ and renal function closely.
DailyMed/FDA (NIH/NLM) — approved Lisinopril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e6898cf8-34c8-44d5-8a86-fbe3be847b16
ARB + spironolactone: serious risk of hyperkalaemia.
Both reduce renal potassium excretion. The combination can cause severe hyperkalaemia. Monitor K+ and renal function.
DailyMed/FDA (NIH/NLM) — approved Losartan label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1dadbe02-289c-4312-9e65-40f3314dcc31
Digoxin + spironolactone: spironolactone reduces renal digoxin excretion and raises its plasma levels (QUADRO 2).
Spironolactone competes with digoxin for renal tubular secretion (P-gp) and may increase digoxin plasma concentrations; it may also interfere with some digoxin immunoassays, overestimating the result. QUADRO 2 of Annex 7 records this interaction in the digoxin section. Clinical relevance is greater with high spironolactone doses and in patients with reduced renal function. Monitor signs of digitalis toxicity (nausea, bradycardia, arrhythmias), renal function and potassium — both hypo- and hyperkalaemia potentiate digoxin arrhythmias. Consider adjusting the digoxin dose and use the same laboratory for digoxin level follow-up.
Spironolactone + digoxin: spironolactone reduces tubular secretion of digoxin and interferes with immunoassays — risk of digitalis toxicity; monitor.
Spironolactone reduces renal digoxin excretion, raising plasma levels and digitalis toxicity (QUADRO 2, Digoxin: "Spironolactone: reduces renal excretion... raises plasma digoxin levels").
Monitor ECG and signs of digitalis toxicity (nausea, bradycardia, arrhythmias).
Digitalis toxicity in a patient taking digoxin + spironolactone.
Monitor digoxin levels when starting spironolactone; consider reducing the digoxin dose.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Digoxin)
ACE inhibitor plus potassium-sparing diuretic raises hyperkalaemia risk.
Combining an ACE inhibitor (ramipril) with a potassium-sparing diuretic (spironolactone) reduces potassium excretion through two pathways: ramipril lowers aldosterone production and spironolactone blocks the aldosterone receptor in the distal tubule. The result is potassium retention, clinically relevant especially in patients with reduced renal function, diabetes or advanced age. This combination is common in heart failure with reduced ejection fraction, where the benefit is proven — what is required is surveillance: potassium and creatinine about 1 week after starting or adjusting, and reassessment if renal function worsens. Severe hyperkalaemia presents with muscle weakness, paraesthesias and arrhythmias and requires immediate correction.
ACE inhibitor + aldosterone antagonist: additive potassium retention, with a hyperkalaemia risk, especially with reduced GFR, diabetes or advanced age. Monitor potassium and creatinine.
Ramipril lowers aldosterone and spironolactone retains potassium; the effect is additive.
Potassium, creatinine.
Hyperkalaemia (weakness, arrhythmia).
Monitor potassium and renal function; avoid in renal impairment.
DailyMed (FDA) — approved Ramipril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3806abdc-6aec-4252-bd79-e2c115b849aa ; approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57d1c333-c229-54aa-e063-6394a90a84ce — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Spironolactone + captopril: additive hyperkalaemic effect when a potassium-sparing diuretic is combined with an ACE inhibitor (QUADRO 2).
Captopril (ACE inhibitor) reduces aldosterone and spironolactone blocks its receptor; both decrease renal potassium excretion and the effect is additive, with a risk of hyperkalaemia. QUADRO 2 of Annex 7 records this interaction in the potassium-sparing diuretic section. The risk is higher in the elderly, renal impairment, diabetes or concomitant potassium supplements and NSAIDs. Monitor potassium and creatinine before and after starting the combination and periodically; avoid potassium supplements and warn about hyperkalaemia symptoms (weakness, palpitations, paraesthesia). Consider dose adjustment or an alternative if GFR is low.
Captopril + spironolactone: additive potassium retention — risk of hyperkalaemia; monitor potassium and renal function.
Potassium-sparing diuretics and ACE inhibitors both raise serum potassium — additive hyperkalaemic effect (QUADRO 2, Potassium-sparing diuretics: "ACEI: additive hyperkalaemic effect").
Monitor potassium and creatinine after starting/adjusting the combination.
Hyperkalaemia (weakness, arrhythmias, ECG changes) in a patient on spironolactone + ACEI.
Monitor serum potassium and renal function; consider dose reduction in at-risk patients (elderly, CKD, diabetes).
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Potassium-sparing diuretics)
Spironolactone + potassium: risk of severe hyperkalaemia.
Spironolactone is a potassium-sparing diuretic that antagonises aldosterone in the distal convoluted tubule, reducing renal potassium excretion. Concomitant potassium supplements (potassium chloride) additively increase the risk of hyperkalaemia, which can be severe and potentially fatal (ventricular arrhythmias, cardiac arrest). The risk is even higher in patients with renal impairment, diabetes or advanced age, and with other potassium-raising drugs (ACE inhibitors, ARBs, other potassium-sparing agents). The combination should generally be avoided; if clinically unavoidable (e.g., severe hypokalaemia in an already treated patient), use the lowest potassium dose, monitor serum potassium frequently and watch the ECG, warning the patient about symptoms such as muscle weakness, palpitations or paraesthesias.
Spironolactone + potassium: risk of severe, potentially fatal hyperkalaemia. Avoid the combination; if unavoidable, monitor serum potassium and ECG.
Spironolactone (potassium-sparing diuretic) reduces renal K+ excretion; additive supplementation may cause potentially fatal hyperkalaemia.
Serum potassium, ECG, renal function.
Weakness, arrhythmias, peaked T waves, cardiac arrest.
Avoid the combination; if unavoidable, monitor potassium frequently and stop the supplement.
DailyMed (FDA) — approved Spironolactone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac487ae2-e15f-4781-bae3-a03058cfcfe4 ; approved Potassium chloride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb56a807-ea94-4edb-9811-a04b19568468 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Spironolactone retains potassium; high dietary potassium or salt substitutes increase the risk of hyperkalaemia.
Avoid potassium-containing salt substitutes and excessive intake of potassium-rich foods.
EMC-UK (MHRA) — approved Spironolactone SmPC: https://www.medicines.org.uk/emc/product/2898/smpc
Spironolactone is contraindicated in hyperkalaemia and severe renal impairment because of the risk of potentially fatal hyperkalaemia.
Do not use with elevated potassium or severely reduced renal function; monitor potassium and creatinine.
EMC-UK (MHRA) — approved Spironolactone SmPC: https://www.medicines.org.uk/emc/product/2898/smpc
Spironolactone crosses the placenta; antiandrogenic effects were seen in male fetuses in animal studies, so caution is advised.
Use only if the benefit outweighs the risk; avoid in the 1st trimester whenever possible.
Canrenone (active metabolite) is excreted into breast milk; use during breastfeeding should be avoided.
In women of childbearing age, rule out pregnancy before starting long-term treatment.
EMC-UK (MHRA) — approved Spironolactone SmPC: https://www.medicines.org.uk/emc/product/2898/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Potassium-sparing diuretic and antihypertensive, acting through aldosterone antagonism. It is effective in oedematous states with secondary hyperaldosteronism (congestive heart failure, hepatic cirrhosis, nephrotic syndrome) and in primary hyperaldosteronism. It may be used alone or with diuretics that act more proximally in the renal tubule.
Specific aldosterone antagonist: binds competitively to the receptors of the aldosterone-dependent sodium-potassium exchange site in the distal convoluted tubule, increasing sodium and water excretion while retaining potassium.
Peak plasma levels of spironolactone occur on average at 2.6 hours and of canrenone at 4.3 hours. Food increases bioavailability by about 95%, so a consistent routine with regard to meals is recommended. Plasma protein binding is over 90%.
Rapidly and extensively metabolised. The active metabolites include canrenone (without the sulphur of the parent molecule) and the sulphur-containing TMS and HTMS, with potencies of about one third relative to spironolactone. The metabolites are excreted mainly in urine and secondarily in bile.
The half-life of spironolactone is about 1.4 hours; the half-lives of the metabolites canrenone, TMS and HTMS are approximately 16.5, 13.8 and 15 hours, respectively. The terminal half-life may be increased in cirrhotic ascites.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
