BMJ 2011; 343:d5228 doi: 10.1136/bmj.d5228 (Published 12 September 2011)
Cite this as: BMJ 2011; 343:d5228
Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study
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Tony Antoniou, clinical pharmacy specialist12,
Tara Gomes, epidemiologist13,
Muhammad M Mamdani, director1345,
Zhan Yao, analyst3,
Chelsea Hellings, project manager3,
Amit X Garg, professor36,
Matthew A Weir, assistant professor of medicine6,
David N Juurlink, division head137
+ Author Affiliations
1University of Toronto, Toronto, ON, Canada
2Department of Family and Community Medicine, St Michael’s Hospital, Toronto
3Institute for Clinical Evaluative Sciences, Toronto
4Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto
5King Saud University, Riyadh, Saudi Arabia
6Division of Nephrology, University of Western Ontario, London, ON, Canada
7Sunnybrook Research Institute, Toronto
Correspondence to: T Antoniou, 410 Sherbourne Street, 4th Floor, Toronto, ON, Canada, M4X 1K2 tantoniou@smh.toronto.on.ca
Accepted 22 July 2011
Abstract
Objectives To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.
Design Population based nested case-control study.
Setting Ontario, Canada, from 1 April 1992 to 1 March 2010.
Participants Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case’s index date.
Main outcome measures Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia.
Results During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17 859/165 754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4)
Conclusions Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.
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