Patients on warfarin who take antibiotics known to interact with the anticoagulant are at a significantly increased risk of serious bleeding events, according to recent research.

Alterations in INR are common among patients who receive antibiotics, noted the study, especially those prescribed antibiotics at high risk of interacting with warfarin: trimethoprim/sulfamethoxazole (TMP/SMX), metronidazole, fluconazole, ciprofloxacin, levofloxacin, azithromycin, and clarithromycin. Cephalexin and clindamycin, which have minimal interactions with warfarin, are considered low-risk antibiotics, said the researchers.

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Their study involved military veterans treated in the Veterans Affairs healthcare system who were prescribed uninterrupted warfarin therapy for more than 30 days between October 2002 and September 2008. Thirty-six of the 8,194 patients who received low-risk antibiotics suffered serious bleeding events compared with 93 of the 14,078 patients who received high-risk antibiotics.

Patients on warfarin therapy exposed to high-risk antibiotics were 50% more likely to suffer serious bleeding events compared with patients on low-risk antibiotics, according to the study. Notably, said the researchers, azithromycin nearly doubled risk of serious bleeding events and TMP/SMX was associated with a more than twofold increase in bleeding risk.

The researchers noted infections alone might cause elevations in INR. They also pointed out that although all patients in the study received antibiotics for infection, only those receiving high-risk medications were at increased risk for bleeding events, which suggests the antibiotic-warfarin interaction is a critical risk factor.

Importantly, evaluating INR in patients on warfarin within 14 days of co-prescribing antibiotics reduced serious bleeding risks by 39%, a finding that emphasized the importance of early monitoring.

Antibiotics, one of the most frequently utilized classes of mediations, have potentially life-threatening interactions with warfarin, one of the most commonly used blood thinners, commented Dr. Michael Lane, assistant professor of medicine at the Washington University School of Medicine in St. Louis. “Our findings suggest that although elevations in INR are common, measuring it within 3 to 14 days of starting antibiotics may decrease the risk of serious bleeding,” he added.

Infections are one of the most common reasons patients are admitted to hospitals, pointed out Dr. Lane. “In order to reduce the risk of serious bleeding events, proactive measures such as repeat INR testing after antibiotic initiation should be strongly considered,” he commented. “This simple intervention could reduce the risk of serious bleeding events among warfarin users.”

The study was published online in the American Journal of Medicine.

—Dan Cook

Reference:

1. Lane MA, Zeringue A, McDonald JR. Serious bleeding events due to warfarin and antibiotic co-prescription in a cohort of veterens. Am J Med. 2014 Mar 19. [Epub ahead of print]