title: Warfarin-antibiotic interactions in older adults of an outpatient anticoagulation clinic.
abstract: BACKGROUND
  Several classes of drugs, such as antibiotics, may interact with warfarin to cause an increase in warfarins anticoagulant activity and the clinical relevance of warfarin-antibiotic interactions in older adults is not clear.
  
  
  OBJECTIVE
  The aim of this study was to determine the effect of oral antibiotics, such as amoxicillin, azithromycin, cephalexin, ciprofloxacin, levofloxacin, and moxifloxacin, on the international normalized ratio (INR) in patients ≥65 years on stable warfarin therapy. The secondary objective was to compare the effect of warfarin-antibiotic interactions on outcomes of overanticoagulation.
  
  
  METHODS
  Data for this retrospective cohort study were collected through a medical record review of patients in an outpatient anticoagulation clinic of a Veterans Affairs medical center. Patients aged ≥65 years on stable warfarin therapy and with at least 1 prescription of an oral antibiotic of interest during the period from January 1, 2003 to March 1, 2011 were included. A mixed-effects repeated-measures ANOVA model was used to determine the effect of antibiotics on the mean change in patients' INR. The Fisher exact test was used to determine the association between the antibiotics and secondary outcomes of overanticoagulation, using cephalexin as the control. Statistical significance was defined as a P value <0.05.
  
  
  RESULTS
  A total of 205 patients had 364 prescriptions for warfarin and antibiotics concomitantly, and there was a significant interaction between antibiotic and time (F(15, 358) = 1.9; P = 0.0221). Antibiotics with a significant increase in INR were amoxicillin (P = 0.0019), azithromycin (P < 0.0001), ciprofloxacin (P = 0.002), levofloxacin (P < 0.0001) and moxifloxacin (P < 0.0001). There was a significant association between type of antibiotic and secondary outcomes of overanticoagulation.
  
  
  CONCLUSIONS
  In older patients on stable warfarin therapy, antibiotics may lead to an increase in INR. However, this may not result in clinically significant outcomes of bleeding or hospitalization, suggesting that antibiotics may be prescribed for older adults taking warfarin as long as their INR is being routinely monitored.
authors.affiliation: Geriatric Pharmacotherapy Program, Department of Pharmacotherapy and Outcomes Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Parinaz K
authors.initials: PK
authors.lastname: Ghaswalla
authors.forename: Spencer E
authors.initials: SE
authors.lastname: Harpe
authors.forename: Daniel
authors.initials: D
authors.lastname: Tassone
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Slattum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States; D014493:United States Department of Veterans Affairs; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D014859:Warfarin