Specific reversal agent Idarucizumab led to immediate, complete and sustained reversal of Dabigatran in healthy individuals
The Lancet has published results from a healthy volunteer study investigating the reversal of the anticoagulant effect of Pradaxa ( Dabigatran etexilate ) by its specific reversal agent Idarucizumab.
The study has shown that Idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of Dabigatran.
The data support the specific reversal agent as a highly targeted treatment option if reversal of the anticoagulant effect is needed, e.g. for urgent interventions.
Idarucizumab was granted Breakthrough Therapy Designation by FDA ( Food and Drug Administration ) and has recently been submitted for approval to the FDA, EMA and Health Canada.
In the healthy volunteer study, participants first received Dabigatran etexilate and then Idarucizumab. The specific reversal agent was given two hours after the last dose of Dabigatran, when Dabigatran concentrations were at peak levels.
After a five-minute infusion of Idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above.
Idarucizumab was well tolerated by the study participants.
Similar results were also seen in elderly and renally impaired volunteers in a study presented at the Annual Meeting & Exposition of the American Society for Hematology in December 2014.
Boehringer Ingelheim is now evaluating Idarucizumab in the RE-VERSE ADTM study, the first study to investigate a reversal agent to a non-vitamin K antagonist oral anticoagulant in patients.
The approved indications for Pradaxa are: a) prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke; b) primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery; c) treatment of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) and the prevention of recurrent DVT and recurrent PE in adults.
Pradaxa, a direct thrombin inhibitor ( DTI ), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.
Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for thrombus formation.
In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment. ( Xagena )
Source: Boehringer Ingelheim, 2015