Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults

Background: Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin. Methods: We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as patients hospitalized for a primary diagnosis of bleeding and were matched with 3 control subjects on age, race, sex, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications. Results: Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All 6 specific antibiotic drug classes examined (azole antifungals [aOR, 4.57; 95% CI, 1.90-11.03], macrolides [aOR, 1.86; 95% CI, 1.08-3.21], quinolones [aOR, 1.69; 95% CI, 1.09-2.62], cotrimoxazole [aOR, 2.70; 95% CI, 1.46-5.05], penicillins [aOR, 1.92; 95% CI, 1.21-2.07], and cephalosporins [aOR, 2.45; 95% CI, 1.52-3.95]) were associated with an increased risk of bleeding. Conclusion: Among older continuous warfarin users, exposure to antibiotic agentsparticularly azole antifungalswas associated with an increased risk of bleeding.