“The anticoagulant effects of Dabigatran (Pradaxa) are important and life-saving for some patients, but there are situations where reversal of the drug’s effects is medically necessary,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology
Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval offers the medical community an important tool for managing patients taking Dabigatran (Pradaxa) in emergency or life-threatening situations when bleeding can’t be controlled.”
The FDA approved Dabigatran (Pradaxa) in 2010 to prevent stroke and systemic blood clots in patients with atrial fibrillation, as well as for the treatment and prevention of deep venous thrombosis and pulmonary embolism. Idarucizumab (Praxbind) is the first reversal agent approved specifically for Dabigatran (Pradaxa) and works by binding to the drug compound to neutralize its effect. Idarucizumab (Praxbind) solution is for intravenous injection.
The safety and effectiveness of Idarucizumab (Praxbind) were studied in three trials involving a total of 283 healthy volunteers taking Dabigatran (Pradaxa) (i.e., people who did not require an anticoagulant). In the healthy volunteers who were given Idarucizumab (Praxbind), there was an immediate reduction in the amount of Dabigatran (Pradaxa) in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours. In this study, the most common side effect from use of Idarucizumab (Praxbind) was headache.
Another trial included 123 patients taking Dabigatran (Pradaxa) who received Idarucizumab (Praxbind) due to uncontrolled bleeding or because they required emergency surgery. In this ongoing trial, based on laboratory testing, the anticoagulant effect of Dabigatran (Pradaxa) was fully reversed in 89 percent of patients within four hours of receiving Idarucizumab (Praxbind). In this patient trial, the most common side effects were low potassium (hypokalemia), confusion, constipation, fever and pneumonia.
Reversing the effect of Dabigatran (Pradaxa) exposes patients to the risk of blood clots and stroke from their underlying disease (such as atrial fibrillation). The Idarucizumab (Praxbind) labeling recommends patients resume their anticoagulant therapy as soon as medically appropriate, as determined by their health care provider.
EMA Recommends Approval of Idarucizumab (Praxbind), a Dabigatran (Pradaxa)-Specific Antidote – The European Medicines Agency (EMA) has recommended the approval of Idarucizumab (Praxbind), a specific antidote to reverse the anticoagulant effect of the direct oral thrombin inhibitor Dabigatran (Pradaxa).
The recommendation for approval follows an accelerated assessment from the Committee for Medicinal Products for Human Use (CHMP). Based on its review, the CHMP recommends use of the Dabigatran (Pradaxa)-specific antidote in Dabigatran (Pradaxa)-treated patients who need to undergo emergency surgery or when life-threatening or uncontrolled bleeding occurs.
As reported by heartwire from Medscape, real-world testing of Idarucizumab (Praxbind) has shown the agent safely and effectively reverses the anticoagulant effects of Dabigatran (Pradaxa). In the RE-VERSE AD study, which was recently presented at the European Society of Cardiology 2015 Congress in London, UK, investigators presented positive data when the agent was tested in patients with atrial fibrillation (AF) who needed emergency surgery or intervention. In the same trial, investigators also showed the drug was effective in managing patients with uncontrolled bleeding.
The risk of bleeding has been a concern with Dabigatran (Pradaxa) since the agent was approved by the European Commission in 2008, according to the EMA. In the US, Boehringer Ingelheim reached a settlement in 2014 and paid out $650 million as part of state and federal lawsuits to patients who claimed Dabigatran (Pradaxa) caused serious adverse events, the majority of which were bleeding-related.
Dabigatran (Pradaxa) is approved in Europe for prevention of stroke and pulmonary embolism in patients with AF as well as for the primary prevention of thromboembolic events in adult patients who have undergone total-hip- or total-knee-replacement surgery. It is also used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE) and to prevent the reoccurrence of DVT/PE.
The CHMP opinion to recommend approval will now be sent to the European Commission, which will make the final decision on a European Union-wide marketing authorization.