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.