Trimethoprim and Perindopril: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Perindopril
Trimethoprim
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
Coadministration of trimethoprim with drugs known to induce hyperkalemia, including potassium-sparing agents, may result in increased risk of hyperkalemia1. In a population based, nested, case-control study (N=165,754), sulfamethoxazole/trimethoprim was found to be 12 times more likely to cause hyperkalemia in elderly patients than amoxicillin 2. Two cases of hyperkalemia have been reported in patients who were taking trimethoprim/sulfamethoxazole concomitantly with an ACE inhibitor. If coadministration of trimethoprim with a potassium-sparing drug is necessary, close monitoring of serum potassium is warranted in such patients 1. Routine monitoring of serum potassium levels in hospitalized patients using trimethoprim/sulfamethoxazole and a potassium-sparing drug is recommended 5.
Why it happens (mechanism)
Additive effects of hyperkalemia
Literature reports
4 reports — tap to read
a) In a population based, nested, case-control study of patients aged 66 years or older administered spironolactone, 6903 of 165,754 patients were admitted to the hospital for hyperkalemia. Among them, 161 were admitted within 14 days of receiving sulfamethoxazole/trimethoprim. Primary analysis revealed an increased risk of hospital admission for hyperkalemia in patients administered sulfamethoxazole/trimethoprim and spironolactone compared with matching controls. An adjusted analysis shown that patients admitted with hyperkalemia were 12.4 times more likely to have received a prescription for sulfamethoxazole/trimethoprim than amoxicillin. In addition, a higher risk of hospital admission was associated with a double-strength formulation of sulfamethoxazole/trimethoprim when compared with single-strength tablets (13.5 vs 9.7-fold increased risk). Analysis also determined, based on the population attributable fraction, that approximately 60% of all hyperkalemia cases in older patients treated with antibiotics for urinary infection would not have taken place if sulfamethoxazole/trimethoprim was not prescribed 2.
b) Hyperkalemia levels greater than 7 mEq/L associated with azotemia (BUN, 33 mg/dL; SCr, 3.3 mg/dL) was noted 20 days after addition of trimethoprim/sulfamethoxazole 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 was asymptomatic; an ECG did not reflect classic signs of hyperkalemia. Drug withdrawal and specific treatment for hyperkalemia, including insulin, dextrose, sodium polystyrene sulfonate, and calcium, was required, with resolution over 36 hours. Nifedipine was substituted for blood pressure control 3.
c) A 40-year-old woman with double lung transplantation developed a Pneumocystis infection 1 year post-transplant. Medications she was stabilized on included enalapril 30 mg daily. High dose trimethoprim/sulfamethoxazole therapy (20 mg/kg/day and 100 mg/kg/day) was instituted. After 9 days of concurrent therapy with trimethoprim/sulfamethoxazole and enalapril, the patient's potassium level reached 6.8 mmol/L. Both medications were discontinued and the patient required treatment for her hyperkalemic condition 4.
d) Among a cohort of 25,849 patients hospitalized patients using a potassium-sparing diuretic and/or a renin-angiotensin system (RAS)-inhibitor, 2054 cases of hyperkalemia were noted. Using trimethoprim/sulfamethoxazole in addition to a potassium-sparing drug was associated with an increased risk of hyperkalemia in hospitalized patients (adjusted OR, 1.65; 95% CI 1.26 to 2.16) compared with using only a potassium-sparing drug. There was a trend of a more pronounced association between hyperkalemia and the concomitant 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 induced by adding trimethoprim/sulfamethoxazole to patients receiving a potassium-sparing drug was 19.5. Routine monitoring of serum potassium levels in hospitalized patients using trimethoprim/sulfamethoxazole and a potassium-sparing drug is recommended 5.
Common questions
Can I take Trimethoprim and Perindopril together?
Increased risk of hyperkalemia Always confirm with your pharmacist or prescriber before making any change.
How serious is the Trimethoprim and Perindopril 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 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 Trimethoprim or Perindopril 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. DOI
- 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 Perindopril
Keep reading about Trimethoprim
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