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Spironolactone Combined with Sulfamethoxazole-Trimethoprim - Drug Interaction May Increase Risk of Sudden Death in Elderly

February 24, 2015

A recent case-control study in patients receiving spironolactone examined rates of sudden death within 14 days of receiving one of the following antibiotics: amoxicillin, ciprofloxacin, nitrofurantoin, norfloxacin, and sulfamethoxazole-trimethoprim. All patients were at least 66 years of age and 90% were 75 years of age or older. Amoxicillin was used as the reference antibiotic in this study (ie, odds ratio of sudden death = 1) for its lack of a known association with sudden death or a drug-drug interaction with spironolactone. The risk of sudden death was highest with sulfamethoxazole-trimethoprim (OR 2.46; 95% CI: 1.55-3.9) compared with amoxicillin. Risk of sudden death was elevated by a lesser extent with ciprofloxacin (OR 1.55; 95% CI: 1.02-2.38) and nitrofurantoin (OR 1.03; 95% CI: 1.03-2.79). Risk of sudden death was not elevated with norfloxacin (OR 0.86; 95% CI: 0.47-1.58). When adjusted for several covariates in a sensitivity analysis, elevated risk of sudden death was no longer statistically significant with sulfamethoxazole-trimethoprim (OR 1.94: 95% CI: 0.93-4.04) or other antibiotics compared with amoxicillin.

The authors suggest that additive hyperkalemia is the most likely reason that sudden death increased when spironolactone and sulfamethoxazole-trimethoprim were used together. The authors recommend avoiding combined use of spironolactone and sulfamethoxazole-trimethoprim if possible due to this drug interaction. If spironolactone and sulfamethoxazole-trimethoprim must be used at the same time, serum potassium monitoring and limiting the duration of combined use are recommended.

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Updated
February 24, 2015, University of Utah, Drug Information Service. Copyright 2015, Drug Information Service, University of Utah, Salt Lake City, UT.