The anticoagulant reversal agent idarucizumab was approved as the antidote to dabigatran via the FDA's accelerated approval program.
One of the biggest advances in the world of nonvalvular atrial fibrillation was the introduction of the novel oral anticoagulants (NOACs) for decreasing thromboembolic risk. With the introduction of these agents, the medical community observed an increase in the number of individuals with high risk for stroke or systemic embolism being effectively treated with oral anticoagulation and also extension of these drugs to treat those with deep venous thromboses or pulmonary emboli. However, the lack of an antidote to these agents gave many clinicians (and patients) equipoise about their safety and willingness to start therapy.
At long last, the first reversal agent for a NOAC (Praxbind [idarucizumab]), which reverses the effects of Pradaxa (dabigatran) was approved by the FDA earlier this month based on data from three trials with 283 subjects. Idarucizumab is a neutralizing humanized monoclonal antibody that is administered intravenously and works to immediately decrease the circulating amount of serum dabigatran. It binds with high affinity to dabigatran and its metabolites.
In the first trial of healthy volunteers, the effects of idarucizumab lasted for at least 24 hours. In the second trial of 123 patients on dabigatran who needed emergency surgery, idarucizumab fully reversed the anticoagulant effect of dabigatran in 89% of patients within 4 hours. Adverse effects included headache, hypokalemia, confusion, constipation, fever, and pneumonia.
This antidote was approved under the FDA’s accelerated approval program for use in emergency situations to allow for earlier access to the drug but ongoing post-marketing surveillance and additional clinical information will be submitted to the FDA by Boehringer Ingleheim, who manufactures both dabigatran and idarucizumab. The current full indication reads:
Praxbind is a specific reversal agent for dabigatran and is indicated in adult patients treated with Pradaxa (dabigatran etexilate) when rapid reversal of its anticoagulant effects is required:
-- For emergency surgery/urgent procedures
-- In life-threatening or uncontrolled bleeding.
It is proposed that idarucizumab be restricted to hospital use only.
FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa [press release]. Silver Spring, MD: United States Food and Drug Administration; October 16, 2015.
Summary of Opinion (initial authorization) Praxbind. European Medicines Agency. London, United Kingdom: September 24, 2015
Praxbind [package insert]. Ridgefield, CT; Boehringer Ingelheim Pharmaceuticals, Inc.; 2015.