Pradaxa is once again in the news. Two very different stories about the drug were published on November 2, 2012. The first was published in the New York Times, written by Katie Thomas and is entitled "A Promising Drug With a Flaw." The second is a FDA Drug Safety Communication regarding Pradaxa.
The FDA undertook a review of the bleeding episodes of Pradaxa to follow-up on a FDA Safety Communication of December 7, 2011. This new safety study concludes that "the results of this Mini-Sentinel assessment indicate that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin, which is consistent with observations from the large clinical trial used to approve Pradaxa (the RE-LY trial)."
The data according to the FDA report shows that intracranial hemorrhage, which is the most dreaded bleeding complication, occurs 1.8 to 2.6 times higher in new users of warfarin than Pradaxa per 100,000 patient days at risk. The rates of gastrointestinal hemorrhage were 1.6 to 2.2 times higher for new users of warfarin than Pradaxa per 100,000 patient days at risk. The excess bleeding in warfarin users is likely due to physicians' inability to control the effect of the drug on patients and the multiple interactions of warfarin with other drugs that patients are often given without a full understanding of their medical conditions.
So what is the problem that has the New York Times so spun up? The problem is that Pradaxa has no way to be reversed. It just has to "wear off," and in that time, the bleeding may not be controllable, and the patient can die. Some conditions like intracranial hemorrhage are so devastating and unpredictable that it often doesn't matter what we do. Further, although there is an antidote for warfarin, let me lead you through the steps.
First ,we have to figure out that you are on warfarin and that you are actually anti-coagulated. The data shows that this only happens about 60% of the time. Second, you have to be "typed and crossed" to find out what blood type you are. Third, the fresh frozen plasma needs to be unfrozen. It can't be placed in a microwave. It is put in a warm water bath and gently rocked back and forth. I am not kidding. You can hop up and down all you want, but you the doctor and you the patient are not getting the fresh frozen plasma until the blood bank is good and ready to give it to you. Then you have to administer it. All of this takes precious time. In the meantime, physicians do what we can, just like always, to support the patient.
The data to approve Pradaxa and Pradaxa itself need to be better understood. First, we physicians give Pradaxa to any patient, but the oldest patient in the study to approve Pradaxa was around 80 years old. The mean age in the RE-LY study to approve was 71.4 +/- 8.6 years. The older you are, the more likely you are to have a poor outcome. Second, as I have blogged about before, the FDA made up the 75 mg dose. The RE-LY study used both a 150 mg does and a 110 mg dose.
More - and there is plenty more - next week.