Warfarin interactions with antibiotics in the ambulatory care setting.
OBJECTIVE
The effect of antibiotic coadministration on the international normalized ratio (INR) in a relatively stable, real-world warfarin population has not been adequately described. Case reports and studies of healthy volunteers do not account for the potential contribution of acute illness to INR variability.


OBJECTIVE
To compare the risk of excessive anticoagulation among patients with stable warfarin therapy purchasing an antibiotic (antibiotic group) with the risk in patients purchasing a warfarin refill (stable controls) and patients with upper respiratory tract infection but not receiving an antibiotic (sick controls).


METHODS
A retrospective, longitudinal cohort study evaluated patients receiving warfarin between January 1, 2005, and March 31, 2011, at Kaiser Permanente Colorado, an integrated health care delivery system. Continuous data were expressed as mean (SD) or median (interquartile range). Multivariable logistic regression analysis was used to identify factors independently associated with a follow-up INR of 5.0 or more. A total of 5857 (48.8%), 5579 (46.5%), and 570 (4.7%) patients were included in the antibiotic, stable control, and sick control groups, respectively. Mean age was 68.3 years, and atrial fibrillation was the most common (44.4%) indication for anticoagulation.


METHODS
Warfarin therapy with a medical visit for upper respiratory tract infection or coadministration of antibiotics.


METHODS
Primary outcomes were the proportion of patients experiencing a follow-up INR of 5.0 or more and change between the last INR measured before the index date and the follow-up INR.


RESULTS
The proportion of patients experiencing an INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick, and stable groups, respectively (P < .001, antibiotic vs stable control group; P < .017, sick vs stable control group; P = .44, antibiotic vs sick control group). Cancer diagnosis, elevated baseline INR, and female sex predicted a follow-up INR of 5.0 or more. Among antibiotics, those interfering with warfarin metabolism posed the greatest risk for an INR of 5.0 or more.


CONCLUSIONS
Acute upper respiratory tract infection increases the risk of excessive anticoagulation independent of antibiotic use. Antibiotics also increase the risk; however, most patients with previously stable warfarin therapy will not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection.
Department of Clinical Pharmacy, Kaiser Permanente Colorado, Aurora 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver.
Nathan P
NP
Clark
Department of Clinical Pharmacy, Kaiser Permanente Colorado, Aurora 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver.
Thomas
T
Delate
Department of Clinical Pharmacy, Kaiser Permanente Colorado, Aurora.
Catherine S
CS
Riggs
Department of Clinical Pharmacy, Kaiser Permanente Colorado, Aurora 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver.
Daniel M
DM
Witt
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Elaine M
EM
Hylek
Division of Hematology, University of Washington, Seattle.
David A
DA
Garcia
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Walter
W
Ageno
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Francesco
F
Dentali
Division of Hematology and Thromboembolism, McMaster University, Hamilton, Ontario, Canada.
Mark A
MA
Crowther
D000368:Aged; D000553:Ambulatory Care; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D014859:Warfarin