NEW YORK (Reuters Health) Feb 03 - An analysis of Medicare data has shown that adults taking warfarin had a twofold increased risk of serious bleeding when an antibiotic was introduced.
Consistent with prior studies, the highest risks were seen with azole antifungals (greater than fourfold increased risk) and cotrimoxazole (nearly threefold increased risk), according to Dr. Jacques Baillargeon of the Department of Preventive Medicine & Community Health, University of Texas Medical Branch at Galveston and colleagues.
Dr. David N. Juurlink, from the Sunnybrook Health Sciences Center in Toronto, Ontario, Canada, who was not involved in the study, told Reuters Health the findings provide "more evidence of interactions between warfarin and antibiotics and a good reminder for clinicians to be aware of this interaction."
Dr. Baillargeon told Reuters Health, "Bleeding risks among continuous warfarin users may be reduced by using antibiotics with low-risk profiles, if appropriate, based on a patient's clinical situation." He said if therapeutic substitution isn't possible, close monitoring of the International Normalized Ratio (INR) "is imperative to reduce the risk of bleeding."
In a report this month in the American Journal of Medicine, he and his colleagues say a "prudent strategy" would be to monitor INR one week after an antibiotic is started and consider more frequent monitoring in patients at higher risk of bleeding.
Using newly available Medicare Part D prescription drug data, the researchers conducted a case-control study nested within a cohort of 38,762 Medicare beneficiaries aged 65 and older who were continuous warfarin users.
Cases were 798 individuals hospitalized for a primary diagnosis of bleeding at any time during 2008. Each case patient was matched to three control subjects on age, sex, race and indication for warfarin (2,394 controls).
Warfarin users exposed to any of the six antibiotic drug classes studied were twice as likely to experience a bleeding event that required hospital admission as those who were not exposed (adjusted odds ratio 2.01), the researchers found.
Antibiotic use was associated with a 2.49 adjusted OR for non-gastrointestinal (GI) bleeding and a 1.68 adjusted OR for GI bleeding.
Individuals whose antibiotic prescriptions started up to 15 days or 16-60 days before the event/index date were more likely to have been hospitalized for bleeding compared with the reference group, patients who were not current antibiotic users (adjusted OR 2.37 and 2.11, respectively).
In contrast, antibiotic-exposed individuals whose antibiotic prescription started more than 60 days before the event/index date did not have a statistically significant increased of bleeding compared with nonusers.
Adjusted ORs for bleeding requiring hospitalization by antibiotic class were 4.57 for azole antifungals; 2.70 for cotrimoxazole; 2.45 for cephalosporins; 1.92 for penicillins; 1.86 for macrolides; and 1.69 for quinolones.
The current study, say the authors, joins a number of other studies indicating that concomitant use of antibiotics and warfarin is associated with a high risk of over coagulation.
As with any study, the current one has its share of limitations, including reliance on ICD-9 bleeding codes, which "are not always accurate or complete," the authors point out.
Also, the authors didn't have data on a number of potential confounding factors, such as diet and use of alcohol, herbal supplements, or over-the-counter medications. "Many over-the-counter medications, including aspirin and nonsteroidal anti-inflammatory drugs, interact with warfarin to increase the risk of bleeding," they note.
They also had no information on the intensity of anticoagulation therapy.
SOURCE: http://bit.ly/AqXyQe
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