While more than 4,000 Pradaxa lawsuits have already been settled, a new group of patients, ignored by Boeringher Ingelheim’s initial payout of $650 million, have begun to file their own legal claims against the company.
Pradaxa, one of three “new generation” blood thinners to hit the US market in recent years, has been linked to an increased risk for excessive, and potentially fatal, bleeding. But all anticoagulants present some risk of bleeding; the point of a blood thinner, after all, is to inhibit the body’s ability to clot. Without clotting, even minor nicks and scrapes can come to bleed endlessly.
So what’s the problem with Pradaxa? Unlike the industry standard, a blood thinner called warfarin, Pradaxa was released without an antidote.
Pradaxa Vs. Coumadin
Doctors have been using warfarin to treat patients with atrial fibrillation for more than 60 years, and it’s proved very effective in breaking down blood clots before they become a problem. But even more importantly, warfarin’s anticoagulant effect can be quickly reversed, either with a dose of vitamin K or an infusion of donor plasma. As thousands of patients have learned after suffering injury or accident, this ability to reverse a blood thinner’s influence on clotting is a true life-saver.
But patients taking Pradaxa were left without a similar reversal agent for five years.
Warning Label “Wholly Inadequate,” Plaintiffs Say
Even more glaring, the drug’s original warning label carried only one reference to an “antidote,” and that reference, which reads “there is no antidote to dabigatran etexilate or dabigatran,” was listed under the product’s information on overdoses. Sections explicitly maintained for “Warnings and Precautions,” including a section on the drug’s “Risk of Bleeding,” were conspicuously free of even the slightest hint that Pradaxa lacked a reversal agent.
It was only on January 17, 2012, after the drug had been available for 15 months, that Boeringher Ingelheim updated Pradaxa’s “Warnings and Precautions” section with the following, FDA-approved language:
“A specific reversal agent for dabigatran is not available.”
As Plaintiffs note in their lawsuits, this “extremely modest” warning only came after thousands of patients had reported serious bleeding incidents, hundreds of which may well have been fatal. Because the blood thinner’s danger was never just theoretical; it was very real from the start.
Thousands Suffer Bleeding Side Effects On Pradaxa
Pradaxa was approved in October of 2010, and instantly hailed as a revolutionary product. Soon, hundreds of thousands of patients had been placed on the drug, and many were switched from a prior regimen of warfarin. Close observers of the pharmaceutical industry, however, noticed a troubling trend almost immediately. Within the first three months of 2011, Pradaxa had already been implicated in nearly 1,000 severe adverse events, according to the industry watchdog Institute for Safe Medication Practices.
Out of 932 adverse events reported during the first quarter of 2011:
- 505 involved hemorrhage, or bleeding
- 120 involved a patient’s death
- 25 led to permanent disability
- 543 patients required hospitalization
In terms of severe bleeding, Pradaxa’s risks appeared to trump every other medication, warfarin included, that were monitored by the Institute for Safe Medication Practices’ QuarterWatch publication. During the same time period, warfarin was only linked to 176 cases of hemorrhage, more than 65% fewer than Pradaxa.
Oddly, many of the adverse event reports filed in relation to Pradaxa were for “seemingly spontaneous bleeding from the gastrointestinal tract,” according to the Project on Government Oversight (POGO), rather than bleeds after traumatic injuries. Intra-cranial hemorrhages also appear to be particularly prevalent.
Perhaps more troubling, most of these injured patients were elderly, at a median age of 80. Nearly 25% were over the age of 84, a fact that led QuarterWatch to question whether or not physicians were regulating patients’ dosages correctly.
Does One Size Really Fit All?
Physicians, however, have little choice in adjusting the dosage of Pradaxa; the drug was approved as a “one-size-fits-all” tablet, 150 milligrams taken twice daily. This uniform dosage was one of Pradaxa’s main selling points. While patients on warfarin must be closely monitored, through routine blood testing every 1 to 4 weeks, Boeringher Ingelheim claimed in effusive marketing materials that patients on Pradaxa would require no such scrutiny.
Plaintiffs have called this assertion into question. So has at least one FDA official, the agency’s Deputy Director of Clinical Science, Dr. Robert Temple. In a presentation on the new class of anticoagulants delivered to European health officials in 2014, Temple doubted the idea that Pradaxa should be treated any differently from warfarin when it comes to dosage: “it is possible that if blood levels were not too variable a single [one-size-fits-all] dose could get most people into proper rage. We know that is not true for [Pradaxa].”
RE-LY Puts Bleeding Risks In Spotlight
But beyond any one detail, Plaintiffs have argued in their lawsuits that the fundamental theme of Boeringher Ingelheim’s marketing is a relatively simple claim: Pradaxa is “safe to use as compared to warfarin.” Where bleeds are concerned, however, even the clinical trial upon which Pradaxa’s initial approval was based, a study called RE-LY, had produced evidence to the contrary.
In the RE-LY trial, researchers compared the safety and efficacy of Pradaxa and warfarin. Pradaxa was associated with a similar rate of major bleeds. While 3.3% of patients taking Pradaxa had suffered excessive bleeding events, 3.6% of patients on warfarin had. But incidents of gastrointestinal bleeding were significantly more prevalent among Pradaxa patients, 1.6% of whom experienced a GI tract bleed, compared to only 1.1% of patients taking warfarin. RE-LY also noted how the risk of bleeding seemed to increase among older people, with Pradaxa patients over the age of 75 being around 20% more likely to suffer a major bleeding event than those on warfarin.
Few of these warning signs were left out of Pradaxa’s prescribing information, but Plaintiffs have noted that, much like the label’s scant reference to a lack of antidote, mentions of an increased bleeding risk were not contained in the labeling’s warning section.
Soon after Pradaxa’s potential risks were publicized, patients and surviving family members began to file lawsuits against Boeringher Ingelheim, claiming the company had failed to warn them of the drug’s dangers and lack of reversal agent.
Boeringher Ingelheim Faces New Wave Of Lawsuits
By 2014, more than 4,000 bleeding lawsuits had been filed, and most were consolidated in the US District Court for the Southern District of Illinois under the watchful eye of the Honorable David Herndon. After discovery, a process in which evidence is gathered, Herndon selected several “bellwether cases,” lawsuits that would proceed to trial first. But before reaching even the first trial, Boeringher Ingelheim decided to settle every one of the lawsuits, including those filed in state courts, for a total of $650 million.
But far more than 4,000 people may have been harmed by Pradaxa, and now, patients and families who were unable to file suit originally have chosen to bring their own legal actions against Boeringher Ingelheim. Their accusations are similar to those leveled during the first round of litigation, claiming that the manufacturer’s warnings remain inadequate, but this new wave of lawsuits is likely to play out in state, rather than federal, courts.
Is There An Antidote To Pradaxa?
In at least one regard, however, the situation has changed significantly. An antidote for Pradaxa, a drug called Praxbind, was approved by the FDA on October 15, 2015. In a clinical trial, Praxbind was able to fully reverse uncontrolled bleeding in 89% of 123 patients within four hours, according to an FDA press release.