Warfarin Interactions With Antibiotics in the Ambulatory Care Setting

Study Questions:

What is the impact of co-prescription of antibiotics for acute respiratory tract infection to patients receiving long-term warfarin therapy on clinically significant international normalized ratio (INR) increases, compared to patients receiving long-term warfarin therapy who are not ill (stable controls) and those who are acutely ill, but not receiving concomitant antibiotics (sick controls)?

Methods:

This was a retrospective, longitudinal cohort analysis conducted at Kaiser Permanente Colorado. Patients were eligible if they received long-term warfarin therapy between 2005 and 2011. Patients were categorized into one of the three groups: antibiotic (purchased a prescription for an oral antibiotic and had at least one INR measurement 3-15 days after the purchase), sick control (purchased guaifenesin with codeine or had a coded provider visit for upper respiratory tract infection and a follow-up INR measured within 15 days), and stable control (purchased a warfarin refill and had a follow-up INR measured within the next 3-30 days). Multivariable logistic regression analysis was used to identify factors independently associated with a follow-up INR of 5.0 or more, one of the primary study outcomes.

Results:

The percentage of patients experiencing a follow-up INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick control, and stable control groups, respectively. Although the risk of an INR of 5.0 or more was greater among the antibiotic and sick control groups compared with the stable control group (p < 0.017), the risk of such an outcome in the antibiotic group compared with the sick control group was not statistically significant (p = 0.44). Clinically relevant bleeding and thromboembolic outcomes were similar across groups. Female gender, active cancer, and elevated baseline INR were independently associated with excessive anticoagulation.

Conclusions:

Upper respiratory illness, independent of antibiotic use, modestly increases the risk of excessive anticoagulation, but does not result in clinically relevant bleeding and thromboembolic outcomes. Co-prescription of antibiotics with long-term warfarin therapy does not result in statistically significant differences in excessive anticoagulation, when compared to stable control patients with upper respiratory infection.

Perspective:

The limitations of the current retrospective analysis aside, the authors provide reassurance about the co-prescription of antibiotics for management of upper respiratory tract infection with long-term warfarin therapy. As the authors acknowledge, ‘the absolute risk of harm associated with co-prescribing antibiotic and warfarin therapy is low.’ Warfarin dosage reduction preemptively may not be necessary when co-prescribing antibiotics. It is not surprising that upper respiratory illness is independently associated with excessive anticoagulation; as the authors postulate, responsible mechanisms for this observation may be reduced oral intake (and decreased consumption of vitamin K-rich foods), use of over-the-counter remedies, and the catabolic impact of fever on clotting factors.

Clinical Topics: Anticoagulation Management

Keywords: Respiratory Tract Infections, Neoplasms, Follow-Up Studies, Warfarin, Colorado, Blood Coagulation Factors, Hemorrhage


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