Upper Gastrointestinal Tract Hemorrhage, Warfarin, and Urinary Tract Antibiotics

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.

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.

— Larry M. Baddour, MD

The journal watch Gastroenterology perspective

The results of this study suggest a possible association of upper GI bleeding with cotrimoxazole use in elderly patients taking warfarin. The retrospective nature of the study cannot control for potential confounding factors. However, the absence of the association with other antibiotics suggests that cotrimoxazole might be different. The confirmation of this association and identification of possible mechanisms of the effect will require future prospective controlled studies and might identify other potential compounds with the same effect. In the interim, this possible effect should be considered in selecting antibiotic therapy for this population, which is at a higher risk for upper GI bleeding.

— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)