Perindopril and Spironolactone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Spironolactone
Perindopril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of hyperkalemia
Interaction Deep Dive
Angiotensin-converting enzyme (ACE) inhibitors lower aldosterone levels and can cause potassium retention1. Concurrent use of potassium-sparing diuretics (spironolactone, canrenoate potassium, aMILoride, triamterene) and an ACE inhibitor has been reported to increase serum potassium by 1 to 1.5 mEq/L when compared to either drug used alone 23. This has occasionally resulted in significant arrhythmias and death 45.
Why it happens (mechanism)
Increased potassium retention secondary to lowered aldosterone levels
Literature reports
2 reports — tap to read
a) A study evaluated the safety of adding an ACE inhibitor (captopril) to a thiazide/potassium-sparing diuretic in 332 hypertensive patients whose blood pressure had not normalized with the diuretics alone. There was only one case of hyperkalemia (6 mmol/liter) and a very low incidence of hypotension (1.6%) 6.
b) The effect of adding spironolactone to an ACE inhibitor and a loop diuretic was evaluated in 214 patients with severe chronic congestive heart failure. Patients were randomized to one of five parallel treatment groups: placebo or spironolactone at a single daily dose of 12.5 mg, 25 mg, 50 mg, or 75 mg for 12 weeks. Hypokalemia (serum potassium less than 3.4 mmol/L) occurred in 10% of placebo-treated patients and in 0.5% of the spironolactone group. The incidence of hyperkalemia (serum potassium greater than or equal to 5.5 mmol/L) was 5% for the placebo group, whereas it was 5%, 13%, 20%, and 24% for the 12.5-, 25-, 50- and 75-mg spironolactone treatment groups, respectively. Predictors of hyperkalemia included the use of ACE inhibitors other than captopril, ACE inhibitor dose, and baseline elevation of serum creatinine or potassium levels. The authors concluded that daily doses of 12.5 mg to 25 mg of spironolactone coadministered with conventional therapy of ACE inhibitors, loop diuretics, and digitalis are relatively safe, provided that serum potassium levels are monitored 7.
Common questions
Can I take Perindopril and Spironolactone together?
Increased risk of hyperkalemia Always confirm with your pharmacist or prescriber before making any change.
How serious is the Perindopril and Spironolactone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Perindopril or Spironolactone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: Prinivil(R), lisinopril. Merck & Co. Inc. Whitehouse Station, NJ, 2003. DailyMed
- Armayor GM & Lopez LM: Lisinopril: a new angiotensin-converting enzyme inhibitor. Drug Intell Clin Pharm 1988; 22:365-372. PubMed
- Burnakis TG & Mioduch HJ: Combined therapy with captopril and potassium supplementation. A potential for hyperkalemia. Arch Intern Med 1984; 144:2371-2372. DOI
- Lakhani M: Complete heart block induced by hyperkalemia associated with treatment with a combination of captopril and spironolactone (letter). Br Med J 1986; 293:271.
- Johnston RT, de Bono DP, & Nyman CR: Preventable sudden death in patients receiving angiotensin converting enzyme inhibitors and loop/potassium sparing diuretic combinations. Int J Cardiol 1992; 34:213-215. PubMed
- Schohn DC, Spiesser R, Wehrlen M, et al: Aldactazine/captopril combination, safe and effective in mild to moderate systemic hypertension: report on a multicenter study of 967 patients. Am J Cardiol 1990; 65:4K-6K. DOI
- Anon: Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (The Randomized Aldactone Evaluation Study (RALES)). Am J Cardiol 1996; 78:902-907.
Keep reading about Spironolactone
Keep reading about Perindopril
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