title: Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study.
abstract: OBJECTIVE
  To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.
  
  
  METHODS
  Population based nested case-control study.
  
  
  METHODS
  Ontario, Canada, from 1 April 1992 to 1 March 2010.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: University of Toronto, Toronto, ON, Canada. tantoniou@smh.toronto.on.ca
authors.forename: Tony
authors.initials: T
authors.lastname: Antoniou
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.forename: Zhan
authors.initials: Z
authors.lastname: Yao
authors.forename: Chelsea
authors.initials: C
authors.lastname: Hellings
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Weir
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000658:Amoxicillin / Q000009:adverse effects; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects*; D016022:Case-Control Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced* / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects*; D009582:Nitrofurantoin / Q000009:adverse effects; D009643:Norfloxacin / Q000009:adverse effects; D016017:Odds Ratio; D009864:Ontario / Q000453:epidemiology; D010343:Patient Admission / Q000706:statistics & numerical data; D012306:Risk; D013148:Spironolactone / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
chemical_list: D000892:Anti-Infective Agents, Urinary; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000658:Amoxicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D009582:Nitrofurantoin; D009643:Norfloxacin