Trimethoprim-sulfamethoxazole plus spironolactone may increase hyperkalemia risk in elderly

Elderly patients taking spironolactone and trimethoprim-sulfamethoxazole may be at increased risk for hospitalization due to hyperkalemia, according to a new study.

Researchers in Ontario, Canada, performed a population-based case-control study of patients 66 years of age and older who were receiving long-term treatment for spironolactone and were admitted to a hospital for hyperkalemia within two weeks of being prescribed trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin or nitrofurantoin. Each patient was matched with up to four controls from the same cohort by age, sex, chronic kidney disease and diabetes, and receipt of one of the study antibiotics within two weeks of the patient's index date. Data were obtained from government databases on prescriptions and hospital admissions.

The study's main outcome measures were the odds ratio (OR) for the association between hospital admission and use of a study antibiotic in the previous 14 days, with adjustments for conditions and other drugs that could affect hyperkalemia risk. Results appear in the Sept. 17 BMJ.

Between April 1, 1992 and March 1, 2010, 6,903 patients were admitted for hyperkalemia. Three hundred six patients were admitted within two weeks of antibiotic use, and of these, 248 (81%) were matched with 783 controls. Overall, 17,859 of 165,754 patients taking long-term spironolactone (10.8%) had also received at least one trimethoprim-sulfamethoxazole prescription. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a substantially increased risk for hospital admission due to hyperkalemia (adjusted OR, 12.4; 95% CI, 7.1 to 21.6). Nitrofurantoin was also associated with increased risk (adjusted OR, 2.4; 95% CI, 1.3. to 4.6), while norfloxacin was not (adjusted OR, 1.6; 95% CI, 0.8 to 3.4).

The authors noted that their study used only administrative data, that outpatient episodes of hyperkalemia could not be quantified, and that residual confounding might have been present, among other limitations. However, they concluded that prescribing trimethoprim-sulfamethoxazole to elderly patients taking spironolactone significantly increased risk for hospitalization due to hyperkalemia compared with the other antibiotics studied.

“Increased awareness of this drug interaction among pharmacists and physicians is needed to ensure that the potential for life threatening hyperkalemia with this drug combination is minimized, either by selection of alternative antibiotics when appropriate or by close monitoring of patients treated with both drugs,” the authors wrote.