What Is Pradaxa?
Pradaxa (dabigatran) is an anticoagulant medication. It is used to prevent blood clot formation in those who suffer atrial fibrillation (AF) and are at risk for stroke. It is also used in patients who have a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) and as a preventative for those conditions in hip replacement surgery.
Pradaxa was developed to be an alternative to the blood thinner, warfarin, which requires frequent blood clotting tests to ensure proper dosing and is known to have serious risks. While warfarin and Pradaxa treat the same condition, they work differently.
Pradaxa works to prevent blood clot formation by inhibiting the clotting protein, thrombin and does not require blood testing. Pradaxa is given as a daily dose of 75 to 150 mg. Patients with kidney problems may need lower dosages and should be carefully monitored.
Pradaxa was approved by the Food and Drug Administration (FDA) in October of 2010. By 2012, nearly 4 million prescriptions had been written and the drug had reached over $1 billion in sales. Though many patients may have been helped by Pradaxa, it has also caused severe side effects in thousands of people and has resulted in at least 500 deaths due to uncontrolled bleeding.
Pradaxa Side Effects
Like all medications, Pradaxa may cause side effects. In most cases, the side effects of Pradaxa are not sever but others can be serious or life-threatening.
Common Side Effects of Pradaxa
Like other anticoagulants, some Pradaxa patients may experience bruising or bleeding due to minor cuts. Patients who are taking Pradaxa should notify doctors and dentists prior to surgical procedures to help avoid bleeding complications.
Symptoms of bleeding may include:
- Frequent nosebleed
- Heavier than normal menstrual period
- Pink or brown-tinged urine
- Unusual bleeding of the gums
Other common side effects may include:
- Stomach pain
Any side effects that occur while using Pradaxa should be reported to a healthcare professional.
Severe Pradaxa Side Effects
Pradaxa use may result in uncontrolled bleeding, which may be fatal. It may also increase the risk for heart attack and has caused severe allergic reactions in some patients.
Pradaxa has been shown to increase the risk of heart attack. A report, published in the Journal of the American College of Cardiology, assessed several trials with more than 30,000 patients. Results showed that Pradaxa users were 33 percent more likely to suffer heart attack when compared with warfarin.
In rare cases, Pradaxa may cause severe allergic reactions. Pradaxa patients should seek immediate medical attention if they experience reaction symptoms such as severe dizziness, rash, trouble breathing, and itching and swelling that occurs in the tongue, throat, and face.
Uncontrolled bleeding is the number one cause of severe injury and death from Pradaxa use. In 2011, more than 2,300 bleeding events were reported. Because it works by inhibiting the clotting enzyme, thrombin, administration of clotting factors is not effective as an antidote and prior to 2015, bleeding caused by Pradaxa was not reversible.
Pradaxa manufacturer Boehringer Ingleheim recommendede that bleeding episodes are treated with hemodialysis to remove Pradaxa from the bloodstream. This treatment has received criticism as many patients who suffer uncontrolled bleeding were not eligible for hemodialysis treatment. Many patients were simply monitored as Pradaxa was cleared from the body.
In 2015, a binding agent known as Praxbind was approved as an antidote. It may be effective at reversing hemorrhage when administered promptly but injury may still occur.
Increased risk factors for Pradaxa bleeding include:
- Being over the age of 75
- Stomach ulcers
- Preexisting kidney problems
- Preexisting or consistent stomach or intestinal bleeding
- Taking other medications that also increase bleeding risk
Symptoms of uncontrolled bleeding may include:
- Severe pain in abdomen or stomach
- Vomiting with blood
- Black, tarry stools
- Abdominal swelling
- Excessive tiredness
- Vision changes or slurred speech
- Weakness on one side of body
At least 500 deaths have been caused by uncontrolled bleeding in patients taking Pradaxa and symptoms of uncontrolled bleeding should be treated as a medical emergency.
Pradaxa Bleeding Complications
Soon after the successful rise of Pradaxa in 2011, 542 deaths were reported to the FDA. Pradaxa was linked to injuries and death more than 800 other drugs that were being prescribed. These medications are closely monitored by the Institute for Safe Medication Practices based in Pennsylvania.
It was noted that internal hemorrhaging and internal bleeding are both dangerous complications associated with Pradaxa usage. This is also a risk associated with Coumadin, but unlike Pradaxa bleeding, internal bleeding from Coumadin can be treated with vitamin K. While there is no antidote for Pradaxa bleeding, the recommended treatment is to filter the medication out from the patient’s blood through dialysis. However, this is a largely ineffective approach to help Pradaxa bleeding.
Many health care professionals assert that Pradaxa bleeding makes the drug too risky for medical use. Even though the medication can help prevent stroke, Pradaxa bleeding makes it a less appealing approach than other medications that are currently available.
FDA Safety Warning
In June of 2011, the first FDA notice was issued for Pradaxa. A public alert notified healthcare professionals and the public about specific storage requirements, stating that Pradaxa should only be dispensed and stored in the original prescription container or blisterpak packaging. The notice stated that improper storage or exposure to moisture could contribute to product breakdown and reduced efficacy.
Due to the number of serious adverse event reports, in December 2011, the Food and Drug Administration issued the first of several warning notices regarding the safety of Pradaxa. The first warning only notified healthcare practitioners and the public that numerous bleeding events had occurred and were being evaluated by the agency. In November of 2012, the FDA issued an update to this warning, stating that recommendations regarding Pradaxa had not changed but indicating that a large study was underway to evaluate bleeding events.
In March of 2012, a report published in the Journal of the American College of Cardiology indicated that evaluation of 30,000 patients showed an increased risk of heart attack when compared to Coumadin. No changes were made to labeling as a result of this study however in December 2012, a new and separate safety warning was issued stating that Pradaxa should not be used in patients with mechanical prosthetic (artificial) heart valves. After a clinical study in Europe was halted, the FDA required that prescribing information include a contraindication against use in patients with artificial heart valves
In April of 2013, Pradaxa’s manufacturer Boehringer Ingelheim, announced that they were adding a “black box warning” to the prescribing information. Information regarding an increased risk of clot formation and stroke when medication is suddenly discontinued was added to the top of prescribing information, enclosed in a black box. This boxed statement warning was similar to that included on other anticoagulants.
In May of 2014, the FDA issued another alert which warned that though elderly Pradaxa patients had a lower risk of stroke, cerebral bleeding, and death than similar Coumadin patients, the risk of major gastrointestinal bleeding was increased. The Medicare study used to provide this data also showed the two drugs had a similar heart attack risk. Again, no changes were required to be made to Pradaxa prescribing information.
Despite continuing reports of adverse events, Pradaxa was approved in November of 2015, to treat additional conditions including prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with hip replacements.
Pradaxa Antidote Approval
In October 2015, the FDA approved an antidote to Pradaxa through its fast-track “accelerated approval” pathway. Praxbind (idarucizumab) works to reverse Pradaxa’s anticoagulant effects by binding to the drug and its metabolites. It is given in emergency situations when bleeding cannot be controlled due to Pradaxa use. Though older medications like Coumadin already had antidotes, Pradaxa is the first of the “new” anticoagulants that can now be reversed.
Full approval for Praxbind was granted in April 2018, after final results from safety studies showed no unexpected results. Most patients show complete reversal of blood thinning effect within 4 hours of Praxbind administration after emergency bleeding event. Healthcare practitioners are advised to resume anticoagulant therapy when appropriate according to patient’s medical status.
In 2014, Boehringer Ingelheim settled nearly 4,000 lawsuits regarding complications caused by Pradaxa use. While many claims were settled, some patients may have elected not to participate in the group settlement and more injuries or deaths due to Pradaxa may have occurred.
Settlements or awards for medical injury may include compensation for medical costs, lost wages, future medical costs and pain and suffering. Patients or loved ones of those who experienced serious injury such as hemorrhage or death, should have their case evaluated by legal experts.