This article is more than 5 years old. Information may no longer be current.
TMP-SMX/spironolactone combination increased sudden death in seniors
Click Here to Manage Email Alerts
Older adults taking a combination of spironolactone and the antibiotic trimethoprim-sulfamethoxazole had more than twice the risk for sudden death than spironolactone users taking amoxicillin, according to researchers from the Canadian Drug Safety and Effectiveness Network.
“More attention needs to be given to the real risk that trimethoprim-sulfamethoxazole [TMP-SMX] can incite life-threatening hyperkalemia in susceptible individuals,” Tony Antoniou, PhD, a research scholar at the department of family and community medicine at St. Michael’s Hospital in Toronto and a scientist at the Institute for Clinical Evaluative Sciences, said in a press release. “And the risks increase when these antibiotics are prescribed with other medications that raise blood potassium, such as spironolactone.”
Tony Antoniou
To assess the mortality risk associated between the two drug types, Antoniou and colleagues conducted a population-based, nested case-control study involving more than 200,000 Ontario residents aged 66 years or older who received spironolactone between 1994 and 2011. Cases of sudden death were identified as those who died within 14 days of receiving a prescription of TMP-SMX, amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin. Each case was matched by age and sex with up to four control patients. The researchers estimated the OR for the association between sudden death and exposure to an antibiotic, with those receiving amoxicillin as the reference group.
While receiving spironolactone, 11,968 residents died of sudden death. Of these, 328 died within 14 days after antibiotic exposure. After adjusting for differences between the groups in the risk of sudden death, TMP-SMX was associated with more than a twofold increased risk for sudden death compared with amoxicillin (adjusted OR=2.46; 95% CI, 1.55-3.9). Relative to amoxicillin, ciprofloxacin (aOR=1.55; 95% CI, 1.02-2.38) and nitrofurantoin (aOR=1.7; 95% CI, 1.03-2.79) also were associated with an elevated risk for sudden death in patients taking spironolactone, but the risk with nitrofurantoin was not apparent in sensitivity analyses, the researchers said. There was no increased risk with norfloxacin (aOR=0.86; 95% CI, 0.47-1.58).
Previous research from members of this team has shown that the same drug combination of TMP-SMX and spironolactone resulted in a 12-fold increased risk for hospital admission with hyperkalemia in older adults.
Antoniou told Infectious Disease News that the heightened risk for sudden death in seniors may reflect terminal hyperkalmia resulting from a drug interaction between trimethoprim and spironolactone.
Based on these findings, the researchers advised clinicians to consider prescribing alternative antibiotics for patients taking spironolactone.
“When patients receiving spironolactone need an antibiotic, clinicians should either select antibiotics that do not contain trimethoprim or limit the dose and duration of trimethoprim-based therapies, while closely monitoring the serum potassium concentration,” Antoniou said. — John Schoen
For more information:
Antoniou T. CMAJ. 2015;doi:10.1503/cmaj.140816.
Antoniou T. BMJ. 2011;343:d5228.
Disclosure: One of the researchers served on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Hoffman-La Roche, Novartis, Novo Nordisk and Pfizer. None of the other researchers report any relevant financial disclosures.