FDA Approves Praxbind (idarucizumab), the First Reversal Agent for Pradaxa (dabigatran etexilate)

 In FDA

The FDA granted accelerated approval of Praxbind (idarucizumab) on October 16, 2015 for use as a specific reversal agent of the anticoagulant effects of Pradaxa (dabigatran etexilate) during emergency surgery/urgent procedures or in episodes of life-threatening or uncontrolled bleeding. This is the first drug to be approved for this indication.  Praxbind is currently not available on the market yet; however, the manufacturer stated that it will be available from major U.S. hospital pharmacy distributors as quickly as possible.

Pradaxa (dabigatran) had been given FDA approval in 2010 as the first direct thrombin inhibitor for the indications of (1) to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (2) for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days and (3) to reduce the risk of recurrence of DVT and PE in patients who have been previously treated.  Unlike Coumadin (warfarin), Pradaxa does not require extensive lab monitoring and is given as 75mg BID or 150mg BID. However, there had been no antidotes to its anticoagulant affect until this point.

Praxbind (idarucizumab) is a monoclonal antibody fragment that is to be given IV only at a recommended dose of 5g, provided as two separate 2.5g/50mL vials to be given consecutively. Praxbind specifically binds to Pradaxa and does not interfere with the anticoagulant effects of other anticoagulants or the coagulation cascade.

Under the accelerated approval process, the FDA approves medications for serious conditions that fill an unmet medical need based on an intermediate clinical endpoint in a clinical trial that is reasonably likely to predict a clinical benefit to patients. This allows patients to gain earlier access to promising new medications, but the company is still required to submit additional clinical information after approval to support the clinical benefits of the drug.

Due to the accelerated approval process, Praxbind has only been studied in healthy patients (i.e. patient who do not require an anticoagulant) in 3 clinical trials of a total of 224 subjects. Therefore, the safety and risk profile for patients who do require an anticoagulant has not been assessed.  Additionally, because the clinical trials were conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to other drugs and the rates may not reflect those observed in clinical practice.

Currently, there are no contraindications for Praxbind.  However there are warnings and precautions in regards to (1) increased thromboembolic risks to the patient’s underlying disease due to reversal of dabigatran’s anticoagulant effects (2) re-elevation of coagulation markers (i.e. activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT)) (3) Hypersensitivity reaction and (4) risk of serious adverse reactions in patients with hereditary fructose intolerance due to sorbitol excipient.

The role of Praxbind in the hospice setting will be limited, due to the limited use of Pradaxa and expense.  Anticoagulant use in generally is not recommended in hospice patients due to the risk of bleeding, especially in the unpredictable declining status of hospice patients.  Exception to this is if the patient has a high level of function, relatively longer prognosis for life and a reasonable quality of life, who is deemed to be at high-risk for thrombotic events.  However, Praxbind does provide a safety net for life-threatening or uncontrolled bleeding in patients using Pradaxa in an otherwise helpless situation, as no other antidote for Pradaxa had been available up until this point.

Click here for more information.

References

  1. Praxbind® [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.
  2. Pradaxa® [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.
  3. FDA. FDA approves Praxabind, the first reversal agent for the anticoagulant Pradaxa.  Accessed October 20, 2015.

Leave a Comment