Beta-Blockers, Trimethoprim-Sulfamethoxazole, and the Risk of Hyperkalemia Requiring Hospitalization in the Elderly

Abstract

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