More than half a century after the blood thinner warfarin was first sold in the United States, a major challenger has come on the scene. Pradaxa (dabigatran), which was approved in October 2010, helps to prevent strokes, requires less maintenance than warfarin and is designed to have fewer side effects. After a year on the market, 16 percent of patients with atrial fibrillation (irregular heartbeat) were taking Pradaxa, compared with 44 percent who were taking warfarin. The remaining patients did not take medication. In late 2011, Xarelto (rivaroxaban) joined the anticoagulant market.
By August 2012, more than 3.7 million U.S. patients had filled prescriptions for Pradaxa. In 2011, Boehringer Ingelheim, the German manufacturer of Pradaxa, spent $464 million to promote the drug, and it has paid off: In 2012, Pradaxa sales passed the $1 billion mark. The anticoagulant therapy market is estimated to bring in $10 billion a year in the United States alone.
Just two years after its arrival, however, Pradaxa is being blamed for more than 500 deaths. Patients and their families report instances of hemorrhaging and uncontrollable bleeding. Some are taking action against Boehringer Ingelheim by filing a Pradaxa lawsuit.
For many years, warfarin — and its brand-name versions Coumadin and Jantoven — has been the standard anticoagulant treatment for patients at risk for strokes and other conditions caused by blood clots. Heparin is another anticoagulant with a longer history, available since 1936, but it is not popular as it must be taken intravenously. Warfarin treatment can be difficult, as it requires regular doctor visits, blood tests and diet restrictions. In addition, side effects of warfarin can be debilitating, causing brain hemorrhages and other types of internal bleeding. A Duke University cardiologist noted that warfarin is one of the leading causes of emergency room fatalities in the United States.
Pradaxa and warfarin both treat patients with atrial fibrillation (AF) who do not have heart disease but are at risk for stroke and blood clots. In clinical trials, Pradaxa outperformed warfarin, reducing the risk of stroke more effectively than warfarin. Pradaxa is also easier to administer, as it does not have the strict requirements that come with warfarin. However, Pradaxa sells at a higher price and still causes some of the same side effects. Warfarin costs about $200 a year, while Pradaxa runs about $3,000 a year.
Warfarin and Pradaxa both prevent blood clots, but they function in different ways. Warfarin thins blood by decreasing the activity of vitamin K , which is essential to the chemical reaction that forms blood clots. Pradaxa inhibits the action of thrombin (a clotting protein) and is part of a drug class called direct thrombin inhibitors. The European Medicines Agency advises doctors to check a patient’s kidney function before prescribing Pradaxa.
Pradaxa is administered in 75, 120 and 150 mg capsules, with most people taking 150 mg capsules twice a day. People with kidney problems may take lower doses. Suddenly discontinuing Pradaxa or missing doses may increase the risk of stroke. Pradaxa is used to treat atrial fibrillation and venous thromboembolism.
Atrial fibrillation (AF) affects more than 2 million Americans and occurs when the heartbeat becomes irregular, which can cause blood to pool in the upper chamber of the heart. It can cause chest pain, heart failure or stroke, which occurs when blood clots travel to the brain. People with AF are around five times more likely to have a stroke than those who do not. For some, AF only occurs occasionally and is not disruptive; for others, it can be a long-term heart problem with serious consequences.
Venous Thromboembolism (VTE)
In Europe and other countries, Pradaxa is used to prevent venous thromboembolism (VTE) following knee or hip replacement surgery. VTE is a lethal disorder that includes deep vein thrombosis (where blood clots form in a deep vein) and pulmonary embolism (where a blood clot in the veins travels to the lungs). The orthopedic procedure of knee or hip surgery puts patients at the highest risk category for developing VTE. Patients begin treatment one to four hours after surgery. Treatment usually lasts for 10 days for knee replacement and around a month for hip replacement.
VTE affects 1.5 million people and causes 500,000 deaths annually. In the 2012 American Heart Association Scientific Sessions, evidence was presented showing that Pradaxa was both safe and effective for VTE. The FDA has not approved this indication for Pradaxa, but Boehringer Ingelheim is in the process of conducting clinical trials to show the efficacy of Pradaxa for VTE. If this indication is approved in the United States , the number of Pradaxa users is expected to drastically increase.
Common Side Effects
Similar to other anticoagulants, Pradaxa may cause bruising or bleeding from minor cuts. Taking blood thinners requires users to alert doctors and dentists before undergoing surgeries or medical procedures in order to prevent bleeding complications. The medication guide that comes with the prescription informs users that the drug can cause bleeding that can be serious and lead to death, therefore users must be aware of side effects and bleeding risks.
Side effects for most people taking Pradaxa will be minimal, which can deceive people into thinking this is a safe drug.
These common side effects include:
- Stomach pain
The risk of bleeding is highest in people:
- Age 75 and over
- With kidney problems
- With stomach or intestine bleeding that is recent or recurring due to a stomach ulcer
To prevent drug interactions, patients need to inform their doctor if they are taking other medications such as anticoagulants, aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).
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Serious Side Effects
In addition to common side effects, Pradaxa can have serious side effects, including uncontrolled bleeding, heart attack, liver failure and even death. The most frequently reported serious side effect was bleeding. Bleeding can cause death, and hemorrhages in the brain and central nervous system can be just as harmful as a stroke, which is what Pradaxa is taken to prevent.
Patients should speak to a physician immediately or seek medical treatment if they experience:
- Unusual bruising
- Coughing up blood
- Vomit that looks like coffee grounds
- Pink or brown urine
- Swelling or joint pain
- Headaches, dizziness or weakness
Pradaxa was one of the most frequently mentioned drugs in the FDA’s database of adverse event reports for 2011, according to QuarterWatch, a publication for the nonprofit Institute of Safe Medication Practices. The FDA received 817 reports of adverse events involving Pradaxa in 2011. QuarterWatch gathered additional reports from manufacturers, databases and health professionals, documenting 3,781 serious adverse events from Pradaxa in 2011; 542 of these events were fatal.
While Pradaxa is supposed to protect people from having a stroke, studies found that patients taking Pradaxa were more likely to have heart attacks and chest pain than those taking warfarin or placebo. In a report published in January 2012 in the Archives of Internal Medicine, researchers from the Cleveland Clinic reviewed seven clinical trials and found Pradaxa was “significantly associated with a higher risk” of heart attacks and chest pain.
Lead researchers Ken Uchino and Adrian V. Hernandez said, “Clinicians should consider the potential of these serious, harmful cardiovascular effects.”
A March 2012 study, published in the Journal of the American College of Cardiology by Dr. Ramin Artang and colleagues, analyzed five trials of 30,470 patients, using information from the U.S. National Institute of Health MEDLINE database. The researchers found “an overall trend toward increased rate of myocardial infarction (heart attack)” linked to Pradaxa compared with warfarin. The study also suggests that doctors use caution in prescribing the drug to patients with coronary artery disease.
That same month, another study by Cleveland Clinic appeared in the Archives of Internal Medicine with similar results, revealing that Pradaxa causes a 33 percent increased risk of heart attack or severe symptoms of heart disease — which can include chest pain, dizziness, shortness of breath and loss of consciousness — compared with warfarin.
QuarterWatch reported more than 2,300 Pradaxa adverse events related to bleeding in 2011. Patients taking Pradaxa and seeking medical attention for falls or minor injuries may find that a hospital visit is not enough.
The FDA released a report in November 2012, concluding that Pradaxa does not present a higher bleeding risk than warfarin. However, the report did not comment on the fact that there is no antidote if a Pradaxa patient starts bleeding. If patients taking warfarin experience bleeding, vitamin K can often stop the bleeding. Boehringer Ingelheim reports that it is working on an antidote.
Japan and Australia have issued a safety warning for Pradaxa regarding bleeding risk. The Japanese Ministry of Health, Labour and Welfare (MHLW) has received 81 reports of serious side effects from Pradaxa, including gastrointestinal bleeding, and responded by sending a safety advisory to physicians. The advisory recommended that physicians monitor patients for signs of bleeding, anemia or renal impairment. The Therapeutic Goods Administration (TGA), Australia’s regulatory authority, has received 203 adverse event reports from Pradaxa use, including 47 serious bleeding events. The TGA encouraged doctors to consider the clinical need and suitability of patients, before subjecting them to unnecessary risk.
After experiencing side effects like hemorrhaging, Pradaxa patients and their families have filed product liability claims against Boehringer Ingelheim. There are more than 250 lawsuits in federal court. They have been combined into a multidistrict litigation (MDL) in the U.S. District Court for the Southern District of Illinois.
Lawyers predict that with the number of people filling Pradaxa prescriptions and the magnitude of adverse events, thousands more lawsuits could follow.