Lisinopril and Eplerenone: 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
Eplerenone
Lisinopril
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 these medicines can raise the potassium level in your blood. Lisinopril is an ACE inhibitor that lowers a hormone called aldosterone, which makes your body hold on to potassium. Eplerenone works in a similar way and also keeps potassium in. Taken together, your potassium can climb higher than with either drug alone.
Too much potassium can affect your heartbeat, so this is worth taking seriously. The good news is that this is very manageable. Please keep taking both exactly as prescribed, and let your doctor or pharmacist know so they can check your potassium with a simple blood test and keep an eye on you.
Effect: Additive hyperkalemia. Lisinopril (ACE inhibitor) suppresses aldosterone; eplerenone is a selective aldosterone-receptor antagonist. Both reduce renal potassium excretion, producing an additive pharmacodynamic effect rather than a metabolic/CYP interaction.
- Direction: Increased serum potassium (reported rises of 1 to 1.5 mEq/L with ACE inhibitor plus potassium-sparing agents).
- Onset: Delayed. Evidence: Probable. Severity: Major (rare arrhythmias/death reported).
- Management: Monitor serum potassium and renal function at baseline and after initiation/dose changes; individualize dosing. Greater caution with renal impairment, diabetes, or added potassium supplements/salt substitutes.
What happens
Increased risk of hyperkalemia
Interaction Deep Dive
By reducing aldosterone concentrations, angiotensin-converting enzyme (ACE) inhibitors can 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 what is seen with either agent given by itself23. In some cases this has led to serious arrhythmias and fatalities45.
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 in heart conditions.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Expect blood tests to check potassium and kidney function, especially when you start or change a dose. Your doses may be adjusted and individualized by your care team.
- Ask before using potassium supplements or salt substitutes, which also contain potassium.
- Report muscle weakness, tiredness, a slow or irregular heartbeat, or palpitations to your doctor or pharmacist promptly.
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 normalized by the diuretics alone. Only one case 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 and a loop diuretic was examined in 214 patients with severe chronic congestive heart failure. Patients were randomized into one of five parallel treatment groups: placebo or spironolactone given as a single daily dose of 12.5 mg, 25 mg, 50 mg, or 75 mg for 12 weeks. Hypokalemia (serum potassium below 3.4 mmol/L) developed in 10% of placebo-treated patients and in 0.5% of the spironolactone group. The rate of hyperkalemia (serum potassium greater than or equal to 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, 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 Lisinopril and Eplerenone together?
Taking eplerenone with lisinopril can push your potassium too high, which can affect your heart, so your care team will monitor your potassium and tailor your doses. Keep taking both as prescribed and report any irregular heartbeat or unusual weakness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Eplerenone 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 Lisinopril and Eplerenone interaction managed?
Your care team can manage this combination safely, and it is sometimes used on purpose in heart conditions. Keep taking both as prescribed unless your prescriber tells you otherwise. Expect blood tests to check potassium and kidney function, especially when you start or change a dose. Your doses may be adjusted and individualized by your care team. Ask before using potassium supplements or salt su… 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 Lisinopril or Eplerenone 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.
Keep reading about Eplerenone
Keep reading about Lisinopril
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