2 FDA moves would boost safety of Pradaxa

Michael Cohen, president of the Institute for Safe Medication Practices, wrote this for the "Check Up" blog.

Users of the new blood thinner Pradaxa, take note. Two new studies suggest 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 the standby 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 mostly older patients in the U.S.

Pradaxa's advantage was that it was easier to use than Coumadin, which requires close monitoring of its clotting effects.

But the FDA approved Pradaxa with only a single standard dose of 150 mg, taken twice a day. The lab test for Coumadin, called INR, was not useful for Pradaxa. And unlike Coumadin, no antidote exists for Pradaxa to halt bleeding quickly should it occur.

For many doctors, Pradaxa-linked bleeding has been a major concern. In January 2012, our QuarterWatch publication noted an unexpected surge of serious and fatal bleeding reports to the FDA, particularly in older patients with a median age of 80. In a study of Pradaxa, 3 percent to 7 percent suffered a major bleed requiring a transfusion in a year's time, depending on age and other factors, and 16 percent had some bleeding.

By the end of 2012, FDA had received 7,387 reports of serious injury linked to Pradaxa, including 1,158 patient deaths. We ranked anticoagulants as the leading drug safety risks of 2011 and 2012. We urged the FDA to reconsider a 110 mg dose of Pradaxa and called for monitoring improvements to identify high-risk older patients.

Doctors now have no option for reducing the dose. In most advanced countries, besides the available 150 mg strength, there's a 110 mg dose recommended for patients age 80 and over and those with risk factors. But the FDA disallowed this lower dose here. A 75 mg dose has been approved, but only for patients with severe kidney disease.

Two studies in the American Journal of Cardiology found that in many older patients, the lower 110 mg dose of Pradaxa is just as effective as the higher dose, while lowering the bleeding risk. The new studies also show that severe bleeding in older patients could be reduced if a lab test were available to identify high-risk patients.

This is because the new studies showed that the same 150 mg dose could make a fivefold difference in the critical blood clotting function.

The blood test, called the Hemoclot Thrombin Inhibitor kit assay, is available in the U.S. only for research. But the test would be valuable because it can help identify the 10 percent of patients at greatest risk.

These options are already available to providers in Canada, Australia, Europe, and elsewhere. The data were collected in 2009 before the approval of Pradaxa and were available to the FDA. So the agency should now reevaluate the need for making these two options available in the U.S. Some patients' lives may depend on it.