Beta-blockers, trimethoprim-sulfamethoxazole, and the risk of hyperkalemia requiring hospitalization in the elderly: a nested case-control study

Background and Objectives — The simultaneous use of beta adrenergic receptor blockers (beta-blockers) and trimethoprim-sulfamethoxazole (TMP-SMX) may confer a high risk of hyperkalemia.

Design, Setting, Participants, and Measurements — Two nested case-control studies were conducted to examine the association between hospitalization for hyperkalemia and the use of TMP-SMX in older patients receiving beta-blockers. Linked health administrative records from Ontario, Canada, were used to assemble a cohort of 299,749 beta-blockers users, aged 66 years or older and capture data regarding medication use and hospital admissions for hyperkalemia.

Results — Over the study period from 1994 to 2008, 189 patients in this cohort were hospitalized for hyperkalemia within 14 days of receiving a study antibiotic. Compared with amoxicillin, the use of TMP-SMX was associated with a substantially greater risk of hyperkalemia requiring hospital admission (adjusted odds ratio, 5.1; 95% confidence interval [CI], 2.8 to 9.4). No such risk was identified with ciprofloxacin, norfloxacin, or nitrofurantoin. When dosing was considered, the association was greater at higher doses of TMP-SMX. When the primary analysis was repeated in a cohort of non-beta-blocker users, the risk of hyperkalemia comparing TMP-SMX to amoxicillin was not significantly different from that found among beta-blocker users.

Conclusions — Although TMP-SMX is associated with an increased risk of hyperkalemia in older adults, these findings show no added risk when used in combination with beta-blockers.