| Primary information |
|---|
| ThPP ID | Th1189 |
| Therapeutic Peptide/Protein Name | Idarucizumab |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 47766 |
| Chemical Formula | C2131H3299N555O671S12 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | 4.5 - 10.8 hrs |
| Description | Idarucizumab, sold under the brandname Praxbind, is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran. Using recombinant expression technology, idarucizumab is produced in a well characterized recombinant (mammalian) CHO cell line and is purified using standard technology. Idarucizumab is composed of a light chain of 219 amino acids and a heavy chain fragment of 225 amino acids, covalently linked together by one disulfide bond between cysteine 225 of the heavy chain fragment and cysteine 219 of the light chain, and has an estimated molecular mass of approximately 47,766 Daltons. |
| Indication/Disease | For use in patients treated with Dabigatran when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures and in life-threatening or uncontrolled bleeding. |
| Pharmacodynamics | The primary PD readout for idarucizumab was reversal of dabigatran-induced anticoagulation. |
| Mechanism of Action | Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran with an affinity 300-fold more potent than the binding affinity of dabigatran for thrombin. The idarucizumab-dabigatran-complex showed a very rapid on-rate and slow off-rate of dabigatran to idarucizumab which results in a half-life of the idarucizumab-dabigatran complex of approximately 260 h. Approximately 20% of the absorbed dose of dabigatran is further metabolised in humans into glucuronides, which have equivalent anticoagulant activity to the parent drug. Idarucizumab also binds and reverses the effects of these acylglucuronides of dabigatran with a similar potency range as for dabigatran. |
| Toxicity | DE/Idarucizumab Dose (mg/kg) for single does in rodents: 0/0, 0/50, 0/175 after single does and 0/0, 0/150 & 0/500 after 4-week with 4-week recovery. 0/0, 12/150, 12/500, 0/500, 12/0 in rhesus monkey after a 2-dose 14-day recovery. |
| Metabolism | Pathways involve biodegradation of the antibody to smaller molecules, i.e., small peptides or amino acids which are then reabsorbed and incorporated in the general protein synthesis. |
| Absorption | NA |
| Volume of Distribution | 8.9 L |
| Clearance | 47.0 mL/min |
| Categories | Anticoagulant |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | NA |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Praxbind |
| Company | Boehringer Ingelheim Pharmaceuticals, Inc. |
| Brand Discription | PRAXBIND (idarucizumab) is a sterile, preservative-free, colorless to slightly yellow, clear to slightly opalescent solution for intravenous administration. PRAXBIND (idarucizumab) is supplied in 2 single-use vials, each containing 2.5 g of idarucizumab in 50 mL formulated as a buffered, isotonic, solution containing acetic acid glacial (10.05 mg), polysorbate 20 (10 mg), sodium acetate trihydrate (147.35 mg), sorbitol (2004.20 mg), and water for injection with an osmolality of 270-330 mOsm/kg and a pH of 5.3-5.7. |
| Prescribed for | PRAXBIND is indicated in patients treated with Pradaxa when reversal of the anticoagulant effects of dabigatran is needed. For emergency surgery/urgent procedures. In life-threatening or uncontrolled bleeding |
| Chemical Name | NA |
| Formulation | 50 mg/mL |
| Physcial Appearnce | injection |
| Route of Administration | IV |
| Recommended Dosage | The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab (see Figure 1). There is limited data to support administration of an additional 5 g of PRAXBIND |
| Contraindication | NA |
| Side Effects | Thromboembolic Risk; Hypersensitivity Reactions; Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient. |
| Useful Link | http://www.rxlist.com/praxbind-drug.htm; http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761025lbl.pdf |
| PubMed ID | 26588018, 25586208, 28222322, 27917717, 27789605, 27543264, 27125504, 27082776, 26651519 |
| 3-D Structure | N.A. |