Pradaxa Bleeding

Patients with non-valvular atrial fibrillation celebrated the release of the new anticoagulant Pradaxa (dabigatran) in October 2010. Whereas warfarin (Coumadin) had been the most frequent option available for reducing the risk of blood clots and stroke, it required regular blood test monitoring and dietary changes, which many patients found inconvenient.

Pradaxa, on the other hand, was marketed as being a no-hassle option, with standardized dosages and no dietary requirements, as well as no need for regular blood test monitoring. Thousands of patients filled prescriptions, with many switching from warfarin to the more convenient option.

It wasn’t long, however, before the FDA started receiving concerning reports regarding side effects, which included Pradaxa bleeding and even death. Though both Pradaxa and warfarin present an increased risk of uncontrolled bleeding, the reports connected with Pradaxa seemed to be much more numerous than those with warfarin, and further, seemed to include an alarming number of patients who had suffered Pradaxa-related deaths.

In May 2012, the Institute for Safe Medication Practices released its “Quarterwatch” report reviewing data from the third and fourth quarters of 2011. They concluded that Pradaxa had the most reports of serious, disabling, and fatal events, accounting for 3,781 domestic reports overall in 2011, including 542 patient deaths. It surpassed all other regularly monitored drugs in reports of hemorrhage, acute renal failure, and stroke.

Warfarin, on the other hand, accounted for 1,106 cases overall in 2011, including 72 deaths.

No antidote for Pradaxa internal bleeding

Patients with atrial fibrillation have hearts that beat erratically and quickly, and are unable to pump with enough strength to get all the blood out of the heart and into the body. As a result, blood can pool and stagnate in the heart, increasing the risk of blood clots, which may travel to the brain and cause a stroke.

Pradaxa “thins” the blood, reducing its ability to clot, which helps reduce the risk of stroke, but at the same time, increases the risk of Pradaxa bleeding. Though both Pradaxa and warfarin have this risk, patients who are injured on warfarin and experience uncontrolled bleeding can be treated. Doctors can administer high doses of vitamin K, which will reverse the blood-thinning property of the drug and allow the blood to clot again, saving the patient’s life in many cases.

Pradaxa, however, has no such readily available antidote, which makes uncontrollable bleeding more likely to lead to Pradaxa-related deaths. Doctors have few options when trying to treat patients, except to do all they can while they wait for the drug to be processed by the body. This can take many hours, and some patients are unable to survive.

FDA looks into reports of Pradaxa related-deaths

For a long while the FDA remained silent concerning the alarming number of reports linked to internal bleeding. Then, in December 2011, the agency released a public safety communication stating they were “evaluating post-marketing reports of serious bleeding events in patients taking Pradaxa.”

They added, however, that they continued to believe that Pradaxa provided an important health benefit when used as directed: “FDA is working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected.”

About a year later, the FDA issued an update to this communication, stating that after evaluating new information about the risks of Pradaxa side effects, they found that the bleeding rates associated with Pradaxa “do not appear to be higher than bleeding rates associated with the new use of warfarin.” The agency concluded they were not changing their recommendations regarding the medication. They did not address the lack of an antidote for Pradaxa, however.

The nonprofit organization Observations Medical Outcomes Project, which was formed by the FDA, questioned the results of this analysis, and recommended the FDA conduct further research.

In early 2013, the FDA published an editorial in the New England Journal of Medicine stating that the large number of adverse event reports associated with Pradaxa may have been influenced by the newness of the drug and the related media coverage.

Reports and medical trials illustrate the danger of Pradaxa side effects

In September 2011, New Zealand began an investigation into the drug after five elderly patients suffered from Pradaxa related deaths and another 36 suffered internal bleeding from Pradaxa. Media outlets reported that some families claimed the fatal chain of events began when the patients switched from warfarin to Pradaxa.

A short time later, Japanese regulators ordered manufacturer Boehringer Ingelheim to warn physicians and patients of the risks associated with the medication, and of the fact that there was no antidote to reverse its effects.

In March 2012, the New England Journal of Medicine published a letter to the editor noting that the original test trial Boehringer used to gain FDA approval of Pradaxa was skewed, in that the age and weight of the participants did not reflect the age and weight of real patients who were actually prescribed the drug.

“We are concerned,” the researchers wrote, “that the potential risks of this medication are not generally appreciated.”

In May 2012, researchers at the Thrombosis and Hemostatis Summit of North America in Chicago stated that in over 2,000 study participants, only .88 percent on warfarin experienced complications, while 11.5 percent of those taking Pradaxa did. Side effects included internal bleeding, deep vein thrombosis, heart attack, and death, and were more likely to affect women and the elderly.

That same month, a case report in the Journal of Neurosurgery detailed the case of an elderly patient who was treated with Pradaxa, experienced uncontrollable bleeding in the brain after a ground-level fall, and later died because doctors had no antidote to stop the bleeding. “To date,” the researchers wrote, “no effective reversal agent for dabigatran in the event of catastrophic hemorrhage has been identified.”

Risk factors for Pradaxa bleeding

Over the past couple of years, scientists have identified some risk factors that can make patients more vulnerable to bleeding.

Patients more susceptible to Pradaxa side effects may include:

• Older patients, typically 70 years and older
• Patients with kidney problems
• Patients with a stomach ulcer or recurrent stomach bleeding
• Patients with a low body weight

In addition, patients who take other medications or herbs that reduce blood clotting may also be at an increased risk of internal bleeding. Such medications may include:

• Over-the-counter pain relievers, like aspirin and ibuprofen
• Other anti-coagulant medications like Plavix and Effient
• Other atrial fibrillation medications like Multaq
• Drugs used to treat infection like Nizoral
• Heparin-containing drugs
• Herbs with blood-thinning properties, such as garlic, turmeric, ginger, white willow bark, cayenne pepper, ginkgo, bromelain, and more

Where does Pradaxa bleeding occur?

According to post-marketing reports and studies, internal bleeding may occur:

• From the gums
• As heavy menstrual bleeding
• Through blood coughing
• In the urine
• As nose bleeds
• Through vomiting
• Bleeding and worsening bruises
• Gastrointestinal bleeding
• Bleeding on the brain or in the skull

Can Pradaxa bleeding be stopped?

Because there is no readily available antidote to Pradaxa bleeding, it can lead to death in some cases. Doctors have tried dialysis, thinking that if they can help the kidneys clean the drug out of the body, they may save the patient, but this internal bleeding treatment has proved difficult. That means that patients who fall and start bleeding may be unable to stop.

Methods doctors may use to stop the bleeding may include:

• Stop administering the drug—it has a half-life of about 12-14 hours. If the patient can survive that long, the blood’s ability to clot will return.
• Kidney dialysis, in an attempt to flush the drug out of the body.
• Stop recently taken Pradaxa from being absorbed in the gut with activated charcoal.

These treatments have not proven to be very effective, however, and doctors are still looking for other ways to address the problem.

When a Pradaxa lawyer can help

Individuals who took Pradaxa and then suffered side effects like uncontrollable bleeding may be able to recover damages in court by filing a Pradaxa lawsuit. Families who lost loved ones to Pradaxa-related deaths can also bring claims against Boehringer Ingelheim.

In August 2012, the Pradaxa MDL (multidistrict litigation) was formed in the Southern District of Illinois, where plaintiffs will share pre-trial discovery. People who believe they have been injured by the anticoagulant are encouraged to consult a qualified Pradaxa lawyer to discuss the pros and cons of filing litigation.