Background: TMP-SMX increases the risk of hyperkalemia when used with spironolactone; however, previous studies have not examined whether the drug interaction is associated with an increased risk of sudden cardiac death, a predictable consequence of hyperkalemia.
Study design: Population-based, nested, case-control study.
Setting: Ontario, Canada.
Synopsis: Investigators identified 11,968 patients aged 66 years or older who suffered sudden death between 1994 and 2011 while receiving spironolactone; for 328 of these patients, death occurred within 14 days of antibiotic exposure. The rate of sudden death in patients receiving TMP-SMX was compared to the rate of sudden death in patients who instead received other study antibiotics.
Compared with amoxicillin, TMP-SMX was associated with a more than twofold increase in the risk of sudden death (OR 2.46, 95%; CI 1.55-3.90). The absolute rate of death of patients taking spironolactone who were prescribed TMP-SMX was 0.74%, compared to 0.35% in patients prescribed amoxicillin.
Because TMP-SMX and spironolactone are common medications, the likelihood of co-prescription leading to drug interaction is high. Although the study does not establish causality, it suggests that alternate antibiotics should be used in elderly patients on spironolactone when possible.
Bottom line: TMP-SMX increases the risk of sudden death in older patients taking spironolactone.
Citation: Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-E143