Upper Gastrointestinal Tract Hemorrhage, Warfarin, and Urinary Tract Antibiotics
Findings from a population-based investigation indicate that cotrimoxazole increased hemorrhage risk among patients on long-term warfarin therapy.
Hemorrhage is a well-known side effect of long-term warfarin use in older patients. Interactions between warfarin and certain other drugs can increase the risk for this complication. In a recent nested case-control study conducted using healthcare databases from Ontario, Canada, researchers examined the risk for upper gastrointestinal (GI) tract hemorrhage among patients receiving both warfarin and antibiotics commonly used to treat urinary tract infections.
The cohort consisted of 134,637 patients aged 66 who had been continuously treated with warfarin for 180 days. Of these patients, 45,972 had received a concomitant prescription for an antibiotic of interest. The 2151 patients (1.6%) who were hospitalized for upper GI tract hemorrhage during the study period were considered cases; up to 10 age- and sex-matched controls were selected for each case.
Cases were nearly four times as likely as controls to have received cotrimoxazole (adjusted odds ratio, 3.84; 95% confidence interval, 2.33–6.33). Ciprofloxacin use was also associated with increased bleeding risk (AOR, 1.94; 95% CI, 1.28–2.95). No significant association was seen between hemorrhage and use of amoxicillin, ampicillin, nitrofurantoin, or norfloxacin.
Comment: Although increasing drug resistance among aerobic gram-negative bacilli has limited the use of cotrimoxazole, this agent is still prescribed for urinary tract infections caused by susceptible pathogens. In addition, it has seen growing use for treating infections with Stenotrophomonas maltophilia, skin and soft tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus, and (as long-term suppressive therapy) certain medical device–related infections.
Among older patients taking warfarin, an antibiotic other than cotrimoxazole or ciprofloxacin should be prescribed. If an alternative is not feasible, both prothrombin time and the international normalized ratio should be monitored closely during and after antibiotic therapy.
Published in Journal Watch Infectious Diseases April 28, 2010
Fischer HD et al. Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: A population-based study. Arch Intern Med 2010 Apr 12; 170:617.
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