On October 16, the Food and Drug Administration (FDA) granted a special accelerated approval to Praxbind (idarucizumab). Praxbind is indicated for patients treated with Pradaxa (dabigatran etexilate) when reversal of the anticoagulant effects are needed for life-threatening or uncontrolled bleeding.
The FDA approved dabigatran 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 (DVT) and pulmonary embolism (PE). Dabigatran is the first in a new class of oral anticoagulants that act by directly blocking the activity of thrombin (factor IIa), the central enzyme in the coagulation cascade responsible for clot (thrombus) formation. The primary advantage of dabigatran is that it has a pharmacokinetic profile that produces predictable anticoagulation responses and does not require frequent laboratory monitoring.
Praxbind is a humanized monoclonal antibody fragment (Fab) designed as a reversal agent specifically for dabigatran. Praxbind works by binding to both free and thrombin-bound dabigatran to completely neutralize its anticoagulant activity without procoagulant effects. Administration of Praxbind results in an almost immediate reversal of dabigatran activity that was fully apparent in 89% of patients within four hours. This effect lasted for at least 24 hours in the majority of patients. The most common side effects reported were headache, hypokalemia, confusion, constipation, fever, and pneumonia.
The recommended dose of Praxbind is 5 grams, provided as two separate vials. In a limited number of patients, between 12 and 24 hours after Praxbind administration, elevated coagulation values were observed. If reappearance of clinically relevant bleeding and elevated coagulation values are observed, administration of an additional 5 gram dose of Praxbind may be considered. However, the safety and effectiveness of repeat treatment has not been established.
Reversing the effect of dabigatran exposes patients to the risk of blood clots and stroke from their underlying disease (such as atrial fibrillation). Patients should resume their anticoagulant therapy as soon as medically appropriate. In clinical studies, no changes in dabigatran’s pharmacokinetics or pharmacodynamics were noted upon re-initiation 24 hours after Praxbind administration.
Praxbind and Pradaxa are both marketed by Boehringer-Ingelheim Pharmaceuticals.
- Boehringer-Ingelheim. Reversal of dabigatran anticoagulant effect with idarucizumab. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine. Retrieved from: http://clinicaltrials.gov/ct2/show/study/NCT02104947 NLM Identifier: NCT02104947
- Food and Drug Administration. (16 October 2015). FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa [Press release]. Retrieved from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm467300.htm
- Ganetsky M, Babu KM, Salhanick SD, et al. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol. 2011 Dec; 7(4):281-7.
- Glund S, Moschetti V, Norris S, et al. A randomized study in healthy volunteers to investigate the safety, tolerability, and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015 May; 113(5):943-51.
- Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomized, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Aug 15; 386(9994):680-90.
- Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Aug 6; 373(6):511-20.
- Pradaxa(R) [package insert]. Ridgefield, CT: Boehringer-Ingelheim Pharmaceuticals; 2015.
- Praxbind(R) [package insert]. Ridgefield, CT: Boehringer-Ingelheim Pharmaceuticals; 2015.
This question prepared by: Justin Loden, PharmD, CSPI (Certified Specialist in Poison Information)
Regarding last week’s Question about Gabapentin-
There were a number of comments about Gabapentin. One of our psychiatrists noted that the discussion was consistent with clinical experience in addiction. Gabapentin has a street value (can trade up or supplement). It is also touted as a means to reduce alcohol use/craving.
Another physician stated that the number of patients with drug seeking behaviors in the primary care clinics caused them to institute a policy that neurontin could not be used off-label (except for diabetic neuropathy).
Thanks for sending in the comments./ ds
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Donna Seger, MD
Tennessee Poison Center
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