Clarithromycin, direct oral anticoagulant concomitant use may confer hemorrhagic risk
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Among older patients on a direct oral anticoagulant, those who took clarithromycin had a small, statistically significant increased risk for major hemorrhage at 30 days vs. those taking azithromycin, researchers found.
“We demonstrated a clear and consistent risk of serious bleeding (requiring presenting to an emergency room or hospitalization) within a short time period (30 days) with clarithromycin and DOAC use,” Manish M. Sood, MD, FRCPC, MSc, associate professor of medicine at University of Ottawa School of Epidemiology and Public Health, scientist at The Ottawa Hospital Research Institute and Jindal Research Chair for the Prevention of Kidney Disease at the University of Ottawa, told Healio.
In a study published in JAMA Internal Medicine, Kevin Hill, MD, of the department of medicine at University of Ottawa in Canada, and colleagues analyzed data from 24,943 patients (mean age, 78 years; 12,493 women) aged at least 66 years who were currently taking a direct oral anticoagulant, particularly apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), dabigatran (Pradaxa, Boehringer Ingelheim) or rivaroxaban (Xarelto, Janssen). These patients were also newly prescribed clarithromycin (n = 6,592; 43% aged 76 to 85 years; 49% women), which was the exposure of interest, or azithromycin (n = 18,351; 43% aged 76 to 85 years; 50% women), which was the active comparator.
“It is a well-suited comparator for clarithromycin because it is prescribed to similar ambulatory patient populations in terms of characteristics, comorbid illnesses, medication use, cause of infection, prescribing physician and hemorrhagic risk,” Hill and colleagues wrote.
The outcome of interest was an ED visit or hospital admission for a major hemorrhage up to 30 days after the antibiotic was dispensed.
Among the cohort, 40% were taking rivaroxaban, 31.9% were taking apixaban and 28.1% were taking dabigatran.
Within 30 days of antibiotic prescription, hospital admission for major hemorrhage occurred in 0.77% of patients prescribed clarithromycin and 0.43% of those prescribed azithromycin (absolute risk difference, 0.34 percentage points; adjusted HR = 1.71; 95% CI, 1.2-2.45).
Similar results were observed in multiple additional analyses.
“[This can have clinical implications on] awareness and recognition that the combination of clarithromycin and DOACs can lead to a higher risk of serious bleeding,” Sood said in an interview. “Furthermore, physicians should take pause before prescribing the combination in individuals for high risk of bleeding (previous bleeding, on additional blood thinning medication such as aspirin, advanced age); consider alternatives if possible and monitor carefully.”
For more information:
Manish M. Sood, MD, FRCPC, MSc, can be reached at msood@toh.on.ca.
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