Lisinopril and Trimethoprim: 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
Trimethoprim
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.
You've been prescribed trimethoprim (an antibiotic) along with lisinopril (a blood pressure medicine). Here's the thing: both of these can nudge your potassium level up a little on their own. When you take them together, those effects can add up, so your potassium could rise higher than we'd like. Very high potassium can affect how your heart beats, so it's worth watching.
The good news is this is easy to manage. Your care team can simply check your potassium with a blood test and keep an eye on things while you're on both. Please keep taking both as prescribed, and let your doctor or pharmacist know if you feel unusually weak, tired, or notice a strange heartbeat.
Effect: Additive risk of hyperkalemia when trimethoprim is combined with lisinopril.
Mechanism: Trimethoprim blocks distal nephron epithelial sodium channels (amiloride-like effect), reducing potassium excretion; lisinopril (an ACE inhibitor) lowers aldosterone, also promoting potassium retention. The effects are additive. Neither is a prodrug relevant to this PD interaction.
- Direction/magnitude: Increased serum K+; observational data show markedly elevated hyperkalemia risk in elderly patients on TMP/SMX vs amoxicillin.
- Onset: Unspecified.
- Evidence: Theoretical/observational plus case reports.
- Management: Monitor serum potassium closely, especially in elderly, renally impaired, or hospitalized patients.
What happens
Increased risk of hyperkalemia
Interaction Deep Dive
When trimethoprim is given together with medications that are known to raise potassium levels, such as potassium-sparing agents, the likelihood of hyperkalemia may rise1. A population based, nested, case-control study (N=165,754) determined that, compared with amoxicillin, sulfamethoxazole/trimethoprim carried a 12-fold greater chance of producing hyperkalemia in elderly patients2. Hyperkalemia has been documented in two patients who were receiving trimethoprim/sulfamethoxazole along with an ACE inhibitor. When it is necessary to combine trimethoprim with a potassium-sparing drug, serum potassium in these patients should be monitored closely1. For hospitalized patients on both trimethoprim/sulfamethoxazole and a potassium-sparing drug, routine checking of serum potassium levels is advised5.
Why it happens (mechanism)
Additive effects of hyperkalemia
How to manage this interaction
This combination is commonly used, and your care team can manage it safely.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may check your potassium with a blood test during treatment, especially if you are older or have kidney concerns.
- Trimethoprim is usually a short course, which helps limit the risk.
- Ask your pharmacist before adding potassium supplements or salt substitutes (these often contain potassium).
- Call your doctor if you notice muscle weakness, tiredness, or an irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a population based, nested, case-control study involving patients 66 years of age or older who were given spironolactone, 6903 of 165,754 patients were hospitalized for hyperkalemia. Of these, 161 were admitted within 14 days of receiving sulfamethoxazole/trimethoprim. The primary analysis showed an elevated risk of hospitalization for hyperkalemia in patients given sulfamethoxazole/trimethoprim together with spironolactone relative to matched controls. An adjusted analysis demonstrated that patients admitted with hyperkalemia were 12.4 times more likely to have been prescribed sulfamethoxazole/trimethoprim than amoxicillin. Furthermore, a greater risk of hospital admission was linked to a double-strength formulation of sulfamethoxazole/trimethoprim compared with single-strength tablets (13.5 vs 9.7-fold increased risk). The analysis also concluded, based on the population attributable fraction, that roughly 60% of all hyperkalemia cases in older patients treated with antibiotics for urinary infection would not have occurred had sulfamethoxazole/trimethoprim not been prescribed 2.
b) Hyperkalemia with levels exceeding 7 mEq/L accompanied by azotemia (BUN, 33 mg/dL; SCr, 3.3 mg/dL) was observed 20 days after trimethoprim/sulfamethoxazole was added for mild acute pyelonephritis to a stable, 3-year regimen of quinapril 20 mg daily in a 74-year-old man being treated for hypertension. The patient had no symptoms; an ECG did not show classic signs of hyperkalemia. Withdrawal of the drugs and specific management of hyperkalemia, including insulin, dextrose, sodium polystyrene sulfonate, and calcium, was necessary, with resolution over 36 hours. Nifedipine was substituted to control blood pressure 3.
c) A 40-year-old woman who had undergone double lung transplantation developed a Pneumocystis infection 1 year after transplant. Her stabilized medications included enalapril 30 mg daily. High dose trimethoprim/sulfamethoxazole therapy (20 mg/kg/day and 100 mg/kg/day) was started. After 9 days of concurrent trimethoprim/sulfamethoxazole and enalapril therapy, the patient's potassium level rose to 6.8 mmol/L. Both drugs were stopped and the patient required treatment for her hyperkalemic condition 4.
d) Within a cohort of 25,849 hospitalized patients using a potassium-sparing diuretic and/or a renin-angiotensin system (RAS)-inhibitor, 2054 cases of hyperkalemia were identified. The use of trimethoprim/sulfamethoxazole in addition to a potassium-sparing drug was associated with a heightened risk of hyperkalemia in hospitalized patients (adjusted OR, 1.65; 95% CI 1.26 to 2.16) compared with use of a potassium-sparing drug alone. There was a trend toward a stronger association between hyperkalemia and the concurrent use of trimethoprim/sulfamethoxazole and potassium-sparing drugs in patients with an estimated GFR of 15 to 29 mL/min. The number needed to harm for hyperkalemia caused by adding trimethoprim/sulfamethoxazole to patients receiving a potassium-sparing drug was 19.5. Routine monitoring of serum potassium levels is recommended in hospitalized patients using trimethoprim/sulfamethoxazole together with a potassium-sparing drug 5.
Common questions
Can I take Lisinopril and Trimethoprim together?
Taking trimethoprim with lisinopril can raise your potassium level because both retain potassium, so keep taking both as prescribed and let your care team check your potassium with a blood test. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Trimethoprim interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Lisinopril and Trimethoprim interaction managed?
This combination is commonly used, and your care team can manage it safely. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may check your potassium with a blood test during treatment, especially if you are older or have kidney concerns. Trimethoprim is usually a short course, which helps limit the risk. Ask your pharmacist before adding potassium supplemen… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
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 Trimethoprim 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 (5)
- Product Information: SEPTRA(R) DS oral double strength tablets, trimethoprim sulfamethoxazole oral double strength tablets. Monarch Pharmaceuticals, Inc. (per FDA), New York, NY, 2013.
- Antoniou T, Gomes T, Mamdani MM, et al: Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ 2011; 343:d5228-. PubMed
- Thomas RJ: Severe hyperkalemia with trimethoprim-quinapril. Ann Pharmacother 1996; 30:413-414. PubMed
- Bugge JF: Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs. J Intern Med 1996; 240:249-251. PubMed
- Butterhoff MH, Derijks HJ, Hermens W, et al: Sulfamethoxazole-trimethoprim-induced hyperkalemia in hospitalized patients using potassium-sparing drugs: an observational study. Sr Care Pharm 2024; 39(7):259-266. PubMed
Keep reading about Trimethoprim
Keep reading about Lisinopril
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