Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

Abstract 

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 agents—particularly azole antifungals—was associated with an increased risk of bleeding.

Keywords:  Antibiotics , Major bleeding , Older adults , Patient safety , Pharmacoepidemiology , Warfarin