====== Idarucizumab ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1hymIO_L1ro2Fr1J6AV7TuZm37Tv60E8mNZhQfheK_4bMRlgpa/?limit=15&utm_campaign=pubmed-2&fc=20250614163322}} Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of [[thrombin]], the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran 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. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.) In the event of bleeding, general supportive measures are recommended and if severe, the use of non-specific hemostatic agents such as [[prothrombin complex concentrate]]s and [[recombinant factor VIIa]] must be considered. In 2015 a specific reversal agent (idarucizumab) is in development ((Enriquez A, Baranchuk A, Redfearn D, Simpson C, Abdollah H, Michael K. Dabigatran for the prevention and treatment of thromboembolic disorders. Expert Rev Cardiovasc Ther. 2015 Apr 5:1-12. [Epub ahead of print] PubMed PMID: 25843430. )). Andexanet alfa and aripazine are currently being evaluated in clinical trials ((Siegal DM. Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. J Thromb Thrombolysis. 2015 Jan 14. [Epub ahead of print] PubMed PMID: 25586208.)) ((Mo Y, Yam FK. Recent advances in the development of specific antidotes for target-specific oral anticoagulants. Pharmacotherapy. 2015 Feb;35(2):198-207. doi: 10.1002/phar.1532. Epub 2015 Feb 3. PubMed PMID: 25644580. )) ((Siegal DM. Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. J Thromb Thrombolysis. 2015 Apr;39(3):395-402. doi: 10.1007/s11239-015-1167-9. PubMed PMID: 25586208.)). Intracranial hemorrhage in patients taking anticoagulants and/or antiplatelets can have either a benign or malignant clinical course. All patients with intracranial hemorrhage taking dabigatran should be admitted for close neurological monitoring and serial imaging ((Wassef SN, Abel TJ, Grossbach A, Viljoen SV, Jackson AW, Howard MA 3rd, Greenlee JD. Traumatic intracranial hemorrhage in patients taking dabigatran: report of 3 cases and review of the literature. Neurosurgery. 2013 Aug;73(2):E368-73; discussion E373-4. doi: 10.1227/01.neu.0000430763.95349.5f. Review. PubMed PMID: 23670031. )). ---- Efficacy of Idarucizmab in Patients with [[Intracranial Hemorrhage]] Preconditioned with [[Dabigatran]] ((Karibe H, Akamatsu Y, Narisawa A, Hayashi T, Kameyama M. [Efficacy of Idarucizmab in Patients with Intracranial Hemorrhage Preconditioned with Dabigatran]. No Shinkei Geka. 2018 Dec;46(12):1117-1120. doi: 10.11477/mf.1436203878. Japanese. PubMed PMID: 30572310. )). ---- Idarucizumab completely reversed the [[anticoagulant]] effect of [[dabigatran]] within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.). "We are very pleased to offer Praxbind®, the first specific reversal agent for a novel oral anticoagulant, now approved by the FDA," said Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. "With this approval, Boehringer Ingelheim is again leading the evolution of anticoagulation care, as we did with the introduction of Pradaxa®. While we anticipate that Praxbind® will be rarely used in clinical practice, the availability of a specific reversal agent has the potential to give physicians and patients added confidence in choosing Pradaxa®." The FDA granted Praxbind® Breakthrough Therapy Designation and the application received Priority Review.5 Praxbind® was approved under an Accelerated Approval Pathway.6 The application included data from healthy volunteers as well as results from an interim analysis of the RE-VERSE AD™ trial (NCT 02104947).2,3,7,8 In the studies, the reversal effects of Praxbind® were evident immediately, within minutes after administration of 5 grams of Praxbind®. No procoagulant effect was observed after the administration of Praxbind®. "The emergence of novel oral anticoagulants, or NOACs, marked a significant advancement in anticoagulation care. While general management strategies for NOAC-related bleeding are available, until today, there was no option for specific and immediate reversal of the anticoagulant effect of a NOAC in a patient in rare emergencies where speed matters, such as life threatening bleeding or the need to quickly perform surgery or interventions," said Dr. Charles Pollack, lead investigator of RE-VERSE AD™, Professor of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA. "The availability of Praxbind® now provides a unique option for reversing anticoagulation in patients taking Pradaxa®." Boehringer Ingelheim is committed to making Praxbind® available as widely as possible. Praxbind® is currently being assessed by different regulatory authorities, including Health Canada. Further submissions are ongoing. About the Praxbind® Clinical Trial Programme Praxbind® was discovered and developed by Boehringer Ingelheim scientists.4 The research programme was initiated in 2009, before Pradaxa® was launched in the U.S. in 2010.4,9 The company completed three phase I trials of Praxbind® in human volunteers, and included these data in the Praxbind® biologics license application (BLA) it submitted to the U.S. Food and Drug Administration.4,6-8 Boehringer Ingelheim is continuing to evaluate Praxbind® in RE-VERSE AD™, a phase III global study that includes patients taking Pradaxa® who have uncontrolled bleeding or require emergency procedures.2,10 The study is the first of its kind in patients, and has been underway since May 2014, enrolling patients in more than 35 countries.11 Data from an interim analysis from RE-VERSE AD™ was also included in the Praxbind® application.2,3,6 About Praxbind® Praxbind® is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.10 Praxbind® binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.10 Boehringer Ingelheim The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 146 affiliates and a total of more than 47,700 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine. Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability. In 2014, Boehringer Ingelheim achieved net sales of about 13.3 billion euros. R&D expenditure corresponds to 19.9 per cent of its net sales. For more information please visit www.boehringer-ingelheim.com This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. Further Media Channels: www.newshome.com www.facebook.com/boehringeringelheim www.twitter.com/Boehringer www.youtube.com/user/boehringeringelheim www.youtube.com/user/CVTV www.pinterest.com/biglobal www.instagram.com/boehringer_ingelheim A Prospective Cohort Study of Idarucizumab for Reversal of Dabigatran-Associated Hemorrhage ((Starke RM, Komotar RJ, Connolly ES. A Prospective Cohort Study of Idarucizumab for Reversal of Dabigatran-Associated Hemorrhage. Neurosurgery. 2015 Dec;77(6):N11-3. doi: 10.1227/01.neu.0000473806.53232.3e. PubMed PMID: 26584318.)) ===== Indications ===== [[Idarucizumab Indications]]. ===== References ===== 1.PRAXBIND® US Prescribing Information, 2015 2.Pollack C. V. et al. Idarucizumab for dabigatran reversal. NEJM. 2015 June 22 (Epub ahead of print). Available at http://dx.doi.org/10.1056/NEJMoa1502000 3.Pollack C.V. Initial results of the RE-VERSE AD trial: idarucizumab reverses the anticoagulant effects of dabigatran in patients in an emergency setting of major bleeding, urgent surgery, or interventions. Oral presentation on Monday 22 June 2015 at the International Society of Thrombosis and Haemostasis 2015 Congress, Toronto, Canada. 4.Boehringer Ingelheim Data on File. 5.Boehringer Ingelheim Press Release – 30 June 2014. U.S. FDA grants Breakthrough Therapy Designation to Pradaxa® (dabigatran etexilate) specific investigational antidote. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/30_june_2014_dabigatranetexilate.html. Last accessed August 2015. 6.Boehringer Ingelheim Press Release – 03 March 2015. Boehringer Ingelheim submits applications for approval of idarucizumab, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2015/03_march_2015_dabigatranetexilate.html. Last accessed August 2015. 7.Glund S. et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113:943–951. 8.Glund S. et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects. Oral presentation on 8 December 2014 at The 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA. Blood 2014; 124: Abstract 344. 9.PRADAXA US Prescribing Information, 2015 10.Pollack C. V. et al. Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost. 2015 May 28;114(1). http://dx.doi.org/10.1160/TH15-03-0192. 11.Boehringer Ingelheim Press Release – 22 May 2015. Antidote for rapid reversal of Pradaxa® (dabigatran etexilate) progresses into next stage of clinical investigation with study in patients. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/22_may_2014_dabigatranetexilate.html  Last accessed August 2015. 12.Pradaxa European Summary of Product Characteristics, 2015. 13.Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95. 14.Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40. 15.Stangier J. et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.