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Hyperkalaemia caused by the use of trimethoprim sulfamethoxazole in patients receiving ACE inhibitors: results of a population study

Trimethoprim / sulfamethoxazole (cotrimoxazole) can cause hyperkalemia and is often prescribed in combination with angiotensin converting enzyme (ACE) inhibitors or with angiotensin receptor blockers. The purpose of a study in Canada was to determine the risk of developing hyperkalemia, which led to hospitalization, in elderly patients who received cotrimoxazole in combination with ACE inhibitors or blockers angiotensin receptors.

A population-based case-control nesting study was conducted in a cohort of patients aged 66 years and older who received long-term treatment with ACE inhibitors or angiotensin receptor blockers. The study group (“case”) of this study was composed of patients hospitalized for hyperkalemia within 14 days of administration of cotrimoxazole, amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin. In each case, up to 4 control patients were identified in the same cohort, comparable in terms of sex, age and the presence / absence of chronic renal disease and diabetes mellitus. The odds ratio was determined to identify a possible relationship between hyperkalaemia leading to patient hospitalization and previous use of antibiotics.

During the 14-year study period, 4,148 cases of hospital admission for hyperkalemia were identified, of which 371 occurred within 14 days of using antibiotics. Compared to amoxicillin, the use of cotrimoxazole increased the risk of developing hyperkalemia requiring hospitalization by almost 7 times (correlated odds ratio 6.7, 95% confidence interval 4.5- 10.0). The risk of developing hyperkalemia has not been identified when using comparisons of antibiotics.

Thus, in elderly patients receiving long-term treatment with ACE inhibitors or angiotensin receptor blockers, the use of cotrimoxazole compared to other antimicrobial drugs leads to a significant increase in the risk of hyperkalemia requiring hospitalization. If it is necessary to prescribe an antibiotic of this type, patients should consider antibiotic treatment options that do not include cotrimoxazole.