Warfarin, antibiotic interactions may not be clinically significant in ambulatory setting

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1. Patients on chronic warfarin who were also receiving antibiotics had an increased INR compared to healthy controls.

2. However, the absolute risk of harm associated with prescribing antibiotics to people on chronic warfarin was low in the ambulatory care setting

Evidence Rating Level: 2 (Good)

Study Rundown: Patients on chronic warfarin and practitioners who care for them must always be strict to maintain an optimal range of anticoagulation. Drug-to-drug interactions pose significant challenges to this. Warfarin’s interactions with antibiotics are particularly difficult because of their short term, intermittent use. Despite this recognition, little is known about the clinical significance of INR variations related to antibiotics in the real world setting. The results of the study suggested that although there was an increase in the INR in patients prescribed antibiotics, it was not clinically relevant in terms of the risk for thromboembolism and significant bleeding, two consequences of chronic warfarin use that most often require hospitalization.

The strengths of this study include the large number of patients in an actual ambulatory care setting with fairly unified documentation and prescribing practices. They also had good patient follow up data in the charts and the outcome events were examined by multiple, blinded reviewers. The weaknesses of this study include the reliance on ICD-9 codes for the clinical outcomes and potential for practitioners to preemptively change the dose of warfarin prior to prescribing antibiotics. Also, the definition of acute illness in this study was “URI type symptoms,” which is very vague and could include a wide variety of infections, each of which could affect the anticoagulation level to varying degrees. Lastly, there is no way to know whether all patients who were prescribed antibiotics actually took the full course.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Systematic overview of warfarin and its drug and food interactions

In-Depth [retrospective cohort study]: The study consisted of patients of Kaiser Permanente Colorado (KPCO) who were on warfarin therapy between January 2005 and March 2011. Active warfarin users were divided into three groups, acutely ill on antibiotics, acutely ill not on antibiotics controls, and healthy controls.  A total of 12,006 patients met the inclusion criteria, of which 5875 received antibiotics, 570 were acutely ill but not prescribed antibiotics, and 5579 were healthy controls. The proportion of patients who had a follow-up INR of 5.0 or more was 3.2% for antibiotic group, 2.6% for sick control, and 1.2% for healthy control (P<0.001 antibiotic vs healthy control group; P<0.017 sick control vs healthy control; P=0.44 antibiotic vs sick control). Clinically relevant bleeding and thromboembolic events (defined as those requiring hospital care) were infrequent (0.1%) and similar across groups (all P>0.05).

By: Anees Daud and James Jiang

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