Amiloride and Lisinopril: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amiloride
No brand names on recordLisinopril
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.
Both of your medicines can raise the amount of potassium in your blood. Amiloride is a "potassium-sparing" water pill, meaning it helps your body hold onto potassium. Lisinopril also lowers a hormone called aldosterone, which has the same effect. Using them together can push your potassium higher than either one alone.
Too much potassium can affect your heartbeat, so this is worth taking seriously. The good news is that your care team can manage this easily with simple blood tests to check your potassium and by tailoring your doses. Keep taking both as prescribed, and talk with your pharmacist or doctor about how often you should have your levels checked.
Effect: Additive hyperkalemia. Lisinopril (ACE inhibitor) reduces aldosterone, decreasing renal potassium excretion; amiloride (potassium-sparing diuretic) independently blocks ENaC-mediated sodium/potassium exchange in the distal nephron. Combined use has raised serum K+ by roughly 1 to 1.5 mEq/L versus monotherapy, occasionally causing serious arrhythmias and death.
- Direction: Pharmacodynamic (additive), not a metabolic interaction.
- Onset: Delayed. Evidence: Probable. Severity: Major.
- Management: Monitor serum potassium and renal function at baseline and periodically; individualize dosing. Greater caution with renal impairment, diabetes, volume depletion, or supplemental potassium.
What happens
Increased risk of hyperkalemia
Interaction Deep Dive
By reducing aldosterone concentrations, angiotensin-converting enzyme (ACE) inhibitors may promote the retention of potassium1. When a potassium-sparing diuretic (spironolactone, canrenoate potassium, aMILoride, or triamterene) is taken together with an ACE inhibitor, serum potassium has been reported to rise by 1 to 1.5 mEq/L relative to the level seen with either agent given on its own23. In some cases this combination has produced serious arrhythmias and death45.
Why it happens (mechanism)
Increased potassium retention secondary to lowered aldosterone levels
How to manage this interaction
Your care team can manage this combination safely, and it is sometimes used on purpose. Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise.
- Expect periodic blood tests to check your potassium and kidney function.
- Your doses may need to be adjusted and individualized by your care team based on those results.
- Avoid adding potassium supplements or potassium-based salt substitutes unless your prescriber approves.
- Report symptoms like muscle weakness, tingling, an irregular or slow heartbeat, or feeling faint.
Bring up any concerns, or any new medicines or supplements, with your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A study assessed the safety of combining an ACE inhibitor (captopril) with a thiazide/potassium-sparing diuretic in 332 hypertensive patients whose blood pressure had not been brought to normal by the diuretics alone. Only a single instance of hyperkalemia (6 mmol/liter) was observed, along with a very low rate of hypotension (1.6%) 6.
b) The impact of adding spironolactone to an ACE inhibitor plus a loop diuretic was studied in 214 patients with severe chronic congestive heart failure. Patients were assigned at random to one of five parallel treatment arms: placebo or spironolactone given once daily at 12.5 mg, 25 mg, 50 mg, or 75 mg over 12 weeks. Hypokalemia (serum potassium below 3.4 mmol/L) was seen in 10% of placebo-treated patients and in 0.5% of those receiving spironolactone. The rate of hyperkalemia (serum potassium at or above 5.5 mmol/L) was 5% in the placebo group, while it was 5%, 13%, 20%, and 24% in the 12.5-, 25-, 50-, and 75-mg spironolactone treatment groups, respectively. Factors predicting hyperkalemia included the use of ACE inhibitors other than captopril, the ACE inhibitor dose, and elevated baseline serum creatinine or potassium levels. The authors concluded that daily doses of 12.5 mg to 25 mg of spironolactone given together with conventional therapy of ACE inhibitors, loop diuretics, and digitalis are relatively safe, as long as serum potassium levels are monitored 7.
Common questions
Can I take Amiloride and Lisinopril together?
Taking amiloride and lisinopril together can push your blood potassium higher, which occasionally causes dangerous heart rhythm problems. Keep taking both as prescribed and let your care team monitor your potassium with blood tests. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amiloride and Lisinopril 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 is the Amiloride and Lisinopril interaction managed?
Your care team can manage this combination safely, and it is sometimes used on purpose. Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise. Expect periodic blood tests to check your potassium and kidney function. Your doses may need to be adjusted and individualized by your care team based on those results. Avoid adding potassium supplements or potassium-based… Management is individual — always follow your own care team's guidance.
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 Amiloride or Lisinopril 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. PubMed
- 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.
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