Idarucizumab
(Praxbind®) Approved
An antidote for rapid reversal of dabigatran-induced anticoagulation indicated for emergency surgery (urgent procedures) and life-threatening or uncontrolled bleeding in patients treated with dabigatran.
BI-655075
CAS No.1362509-93-0
1-225-Immunoglobulin G1, anti-(dabigatran) (human-Mus musculus γ1-chain) (225→219′)-disulfide with immunoglobulin G1, anti-(dabigatran) (human-Mus musculus κ-chain)
Other Names
- BI 655075
- Idarucizumab
- Praxbind
Protein Sequence
Sequence Length: 444, 225, 219multichain; modified (modifications unspecified)
Idarucizumab, sold under the brand name Praxbind, is a monoclonal antibody designed for the reversal of anticoagulant effects ofdabigatran.[1][2]
This drug was developed by Boehringer Ingelheim Pharmaceuticals. A large study sponsored by the manufacturer found that idarucizumab effectively reversed anticoagulation by dabigatran within minutes.[3] It was FDA approved in October 2015.[4] In the United States the wholesale cost is $3500 US.[5]
On October 16, 2015, the U. S. Food and Drug Administration granted accelerated approval to idarucizumab (Praxbind Injection, Boehringer Ingelheim Pharmaceuticals, Inc.) for the treatment of patients treated with dabigatran (Pradaxa) when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures, or in life-threatening or uncontrolled bleeding.
The approval was based on three randomized, placebo-controlled trials enrolling a total of 283 healthy volunteers who received either dabigatran and idarucizumab or dabigatran and placebo. The primary endpoint in healthy volunteer trials was the reduction of unbound dabigatran to undetectable levels after the administration of 5 g idarucizumab. This reduction of dabigatran plasma concentration was observed over the entire 24 hour observation period.
These trials are supported by an ongoing open-label trial in which data from 123 patients receiving dabigatran who had life-threatening or uncontrolled bleeding, or who required emergency surgery/urgent procedures was available for evaluation. This open-label trial continues to enroll and follow patients. The primary endpoint is the reversal of dabigatran’s anticoagulant effect (measured by ecarin clotting time or dilute thrombin time) in the first four hours after administration of 5 g idarucizumab. In these 123 patients, the anticoagulant effect of dabigatran was completely reversed in more than 89% of patients within four hours of receiving idarucizumab. Between 12 and 24 hours after idarucizumab administration, elevated coagulation parameters have been observed in a limited number of patients.
Safety data were evaluated in 224 healthy volunteers who received at least one dose of idarucizumab and 123 patients who received idarucizumab. Headache was the most common adverse event reported in more than 5% of healthy volunteers. Among the 123 patients treated with idarucizumab in the ongoing open-label trial, adverse events reported in more than 5% of patients were hypokalemia, delirium, constipation, pyrexia and pneumonia.
Praxbind is the first approved reversal agent. It is specific for dabigatran.
Continued approval for this indication may be contingent upon the results of completion of the ongoing open-label trial.
The recommended dose for idarucizumab is 5 g (2.5g per vial) administered intravenously as two consecutive 2.5 g infusions or bolus injection by injecting both vials consecutively one after another via syringe.
References
- Statement On A Nonproprietary Name Adopted By The USAN Council – Idarucizumab, American Medical Association.
- World Health Organization (2013). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 109” (PDF). WHO Drug Information 27 (2).
- Pollack, Charles V.; Reilly, Paul A.; Eikelboom, John; Glund, Stephan; Verhamme, Peter; Bernstein, Richard A.; Dubiel, Robert; Huisman, Menno V.; Hylek, Elaine M. (2015-08-06).“Idarucizumab for Dabigatran Reversal”. The New England Journal of Medicine 373 (6): 511–520. doi:10.1056/NEJMoa1502000. ISSN 1533-4406. PMID 26095746.
- “Press Announcements – FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa”. www.fda.gov. Retrieved 2015-10-17.
- Elia, Joe. “Dabigatran-Reversal Agent Price Set”. Retrieved 20 October 2015.
| Monoclonal antibody | |
|---|---|
| Type | Fab fragment |
| Source | Humanized (from mouse) |
| Target | Dabigatran |
| Clinical data | |
| Trade names | Praxbind |
| Identifiers | |
| CAS Number | 1362509-93-0 |
| ATC code | V03AB37 (WHO) |
| IUPHAR/BPS | 8298 |
| ChemSpider | none |
| Chemical data | |
| Formula | C2131H3299N555O671S11 |
| Molar mass | 47.8 kg/mol |
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