There is no question that dabigatran – produced by German pharmaceutical giant Boehringer-Ingeheim (BI) and sold under the brand name Pradaxa – is dangerous and has resulted in fatal hemorrhaging in as many as 10% of patients for whom it has been prescribed. Most recently, a 92-year-old patient died prematurely after ingesting only a single dose.
Despite this, the use of Pradaxa is on the rise. Disturbingly, this includes “off-label” use of the medication. For those who aren't familiar with the term, “off-label” use refers to instances in which a physician prescribes a medication for a condition it was not originally designed to treat. Pradaxa is an anticoagulant (often called a “blood thinner,” though this is not an accurate description) that suppresses the action of the blood enzyme (thrombin) responsible for clotting. Pradaxa is specifically intended to treat patients who have a condition known as atrial fibrillation (AF), which causes irregular heartbeat and can increase the risk of stroke, and at least one other risk factor such as high blood pressure, diabetes, advanced age or a history of stroke. It is also used for patients who have had hip or knee replacements in order to prevent clotting.
According to a report on the website Heartwire, however, use of dabigatran – primarily off-label – has been on the rise, despite reports of adverse events and the introduction of a new anti-clotting medication from Bayer, rivaroxaban (sold under the brand name Xarelto). Primarily, Pradaxa is being prescribed to patients by cardiologists for general heart disease, venous thrombosis (a condition in which a clot forms within a blood vessel) and transient ischemic attacks (so-called “mini-strokes”).
Pradaxa's appeal for physicians is understandable: there are far fewer interactions with other medications, thereby requiring far less patient monitoring. In addition, the Food and Drug Administration (FDA) as well as the American Heart Association (AHA) continue to trumpet the fact that bleeding events are approximately the same for both dabigatran and the old standby, warfarin (Coumadin). Dr. Elliot Anatman of Harvard Medical School says he believes that “if physicians adhere to the recommendations for adjusting the dose if there is diminished kidney function, patients who receive a drug like dabigatran will be treated optimally.” Another physician, Dr. David Callans, a Philadelphia cardiologist, told the MedPage Today that the FDA's announcement was “nice in response to the rather tiresome lawyer ads about Pradaxa on television.”
The FDA “continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label.”
Significantly, while there is agreement on the bleeding risk for patients, neither the FDA, AHA nor BI mention the complete unavailability of an antidote. Excessive bleeding caused by warfarin can be reversed by dosing the patient with Vitamin K, but because of the way dabigatran operates, there is no reliable way to stop it. An article published by Reuters in June of 2012 reported that BI was “working at developing an antidote.” However, there is as of yet no indication that such an antidote has been found – and laypeople posting on various forums and blogs around the World Wide Web are still expressing surprise at the fact.
N/A. “Pradaxa (dabigatran etexilate mesylate): Drug Safety Communication - Safety Review of Post-Market Reports of Serious Bleeding Events.” U.S. Food and Drug Administration, 2 November 2012. Available at http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm282820.htm
N/A. “Pradaxa.” European Medicines Agency, 9 April 2012.
Neale, Todd. “AHA: No Excess Bleeding Risk with Dabigatran.” MedPage Today, 03 November 2012. Available at http://www.medpagetoday.com/MeetingCoverage/AHA/35724.
Stiles, Steven. “Dabigatran Use Climbing in U.S., On and Off-Label.” Heartwire, 28 September 2012. Available at http://www.theheart.org/article/1452779.do