Two FDA moves would reduce bleeding risks with Pradaxa


If you use the new anticoagulant (blood thinner) Pradaxa (dabigatran), take note. Recent publication of two studies suggests that a lower dose and a lab test may limit the drug’s major drawback: high rates of bleeding.

Pradaxa was approved in late 2010 as an alternative to standard therapy with the blood thinner Coumadin (warfarin). Both are effective in reducing disabling strokes in patients with atrial fibrillation, a heart disorder that affects about 2.5 million people in the US. Pradaxa’s advantage over Coumadin is that, in the US, the drug does not require close laboratory monitoring of its clotting effects, and it does not require dose adjustments. The US Food and Drug Administration (FDA) approved Pradaxa with just one standard dose, 150 mg taken twice a day.

For many doctors, the risk of bleeding with Pradaxa has been a major concern. The lab test used to monitor the effects of Coumadin, called an international normalized ratio (INR), does not identify Pradaxa patients at high risk of bleeding. And unlike Coumadin, no antidote exists for Pradaxa to stop bleeding quickly should it occur.

One study of Pradaxa found that, within a year’s time, 3% to 7% of users, depending on age and other factors, suffered a major bleed requiring a blood transfusion. Another 16% had some bleeding. In January 2012, a QuarterWatch publication from the Institute for Safe Medication Practices (ISMP) identified an unexpected surge of reports to FDA about serious and fatal bleeding in patients who took Pradaxa, particularly older patients with an average age of 80. By the end of 2012, FDA had received 7,387 reports of serious injury linked to Pradaxa, including 1,158 patient deaths. In fact, the use of blood thinners was the leading drug safety risk in both 2011 and 2012.

Since 2011, ISMP has urged FDA to reconsider approving a lower dose of Pradaxa. We also called for monitoring improvements to identify older patients at high risk for bleeding. Right now, doctors have no option for reducing the dose. In other countries, besides the 150 mg strength, there is also a 110 mg (twice daily) dose recommended for patients age 80 and older and those with other risk factors. But FDA has not approved this lower dose in the US. A 75 mg twice daily dose has been approved by FDA, but only for patients with severe kidney disease.

Two studies published in the Journal of the American College of Cardiology in 20131 and 20142 found that, in many older patients, the lower 110 mg (twice daily) dose of Pradaxa is just as effective as the higher 150 mg (twice daily) dose, while the risk of bleeding is lower. The studies showed that a dose of 150 mg twice daily was extremely risky, mostly because there were 5-fold or greater differences from person to person in how much of the medicine was actually in the blood after this dose. The studies also show that the risk of severe bleeding in older patients may be reduced if a lab test is used to identify patients at high risk for that problem. That blood test, called the Hemoclot Thrombin Inhibitor assay, is not FDA-approved for use in the US except for research.

These options—the 110 mg dose and the blood test—are already available to healthcare providers in Canada, Australia, Europe, and elsewhere. The data in these studies were collected in 2009 and were available to the FDA before the approval of Pradaxa. We strongly believe the agency should now reevaluate the need for making these two options available in the US.


1)         Eikelboom JW, Connolly SJ, Hart RG, et al. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol. 2013;62(10):900–7.

2)         Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients. J Am Coll Cardiol. 2014;63(4):321–8.

Created on March 27, 2014

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