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

• Published in: The American journal of medicine Vol. 125; no. 2; pp. 183 - 189
• Main Authors: Baillargeon, Jacques, Holmes, Holly M., Lin, Yu-Li, Raji, Mukaila A., Sharma, Gulshan, Kuo, Yong-Fang
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2012; Elsevier; Elsevier Sequoia S.A
• Subjects: Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Biological and medical sciences; Case-Control Studies; Comorbidity; Drug Interactions; Female; General aspects; Hemorrhage; Hemorrhage - chemically induced; Humans; Insurance Claim Review - statistics & numerical data; Internal Medicine; Logistic Models; Major bleeding; Male; Medical sciences; Medicare Part D - statistics & numerical data; Older adults; Older people; Patient safety; Pharmaceuticals; Pharmacoepidemiology; Pharmacology. Drug treatments; Risk factors; United States; Warfarin; Warfarin - adverse effects; Warfarin - therapeutic use; United States; Pharmacoepidemiology; Patient safety; Warfarin; Antibiotics; Older adults; Major bleeding; Human; Coumarine derivatives; Concurrent; Use; Risk; Anticoagulant; Hemorrhage; Medicine; Antivitamin K; Antibiotic; Concomitant disease; Risk factor; Antibacterial agent; Elderly
• ISSN: 0002-9343; 1555-7162; 1555-7162
• DOI: 10.1016/j.amjmed.2011.08.014

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. 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. 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. Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding.