Concomitant use of ACE inhibitors, ARBs with trimethoprim/sulfamethoxazole associated with increased risk of hyperkalemia-associated hospitalization in older adults, data indicate

Among older adults receiving long-term therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), those who receive a concomitant prescription for the antibiotic combination of trimethoprim/sulfamethoxazole are significantly more likely to develop hyperkalemia requiring hospitalization than are those who receive other antibiotics, according to data from a population-based, nested, case-control study. The study researchers noted that ACE inhibitors...

Among older adults receiving long-term therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), those who receive a concomitant prescription for the antibiotic combination of trimethoprim/sulfamethoxazole are significantly more likely to develop hyperkalemia requiring hospitalization than are those who receive other antibiotics, according to data from a population-based, nested, case-control study.

The study researchers noted that ACE inhibitors and ARBs both have the potential to cause serious hyperkalemia, particularly in patients with other risk factors for the condition, which include the use of drugs that impair potassium excretion. They added that trimethoprim is structurally and pharmacologically similar to potassium-sparing diuretics, and that trimethoprim/sulfamethoxazole, ACE inhibitors, and ARBs are all widely used, such that the antibiotic combination is likely to be prescribed in patients who are already taking an ACE inhibitor or an ARB.

The investigators assessed the risk of hyperkalemia-associated hospitalization in patients aged 66 years or older who resided in Ontario, Canada, between April 1, 1994, and March 31, 2008. All participants were receiving long-term treatment with an ACE inhibitor or an ARB when they received a prescription for 1 of 5 antibiotics--trimethoprim/sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin.

Cases were those participants who were hospitalized within 14 days of their antibiotic prescription. Each case was matched with up to 4 controls, with cases and controls matched for age at the index date, sex, and the presence or absence of renal disease and diabetes.

During the 14-year study period, there were 4,148 hospital admissions involving hyperkalemia among 439,677 older adults included in the analysis. Of these hospitalizations, 371 occurred within 14 days of the patient receiving 1 of the 5 study antibiotics, and more than half of these 371 hospitalizations occurred in patients who received trimethoprim/sulfamethoxazole.

Relative to amoxicillin use (the reference antibiotic), the odds of a hyperkalemia-associated hospitalization were 6 to 7 times greater with use of trimethoprim/sulfamethoxazole. Specifically, the crude and adjusted odds ratios were 6.2 (95% CI, 4.3-9.1) and 6.7 (95% CI, 4.5-10), respectively, with the latter analysis adjusted for concomitant medical conditions and drug classes that could be associated with an increased risk of ACE inhibitor- or ARB-associated hyperkalemia, among other factors.

By contrast, no such increase in risk was found with the use of the other antibiotics evaluated.

"These findings support the notion of a potentially life-threatening drug interaction between trimethoprim and inhibitors of the renin-angiotensin-aldosterone system," the researchers wrote. (Antoniou T, et al. Arch Intern Med 2010;170:1045-1049.)