Idarucizumab Molecular Weight Daltons 47766 Chemical Formula C

Idarucizumab Molecular Weight (Daltons) : 47766 Chemical Formula : C 2131 H 3299 N 555 O 671 S 11 Half-Life : 4. 5 - 10. 8 hrs

• Description Idarucizumab, sold under the brandname Praxbind, is a humanized monoclonal antibody fragment (Fab) derived from an Ig. G 1 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 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 idarucizumabdabigatran-complex showed a very rapid on-rate and slow offrate 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. • Volume of distribution 8. 9 L • Clearance 47. 0 m. L/min • Category Anticoagulant

Brands : Praxbind Company : Boehringer Ingelheim Pharmaceuticals, Inc. Description : 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 m. L 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 m. Osm/kg and a p. H of 5. 3 -5. 7. Used for/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 Formulation : 50 mg/m. L Form : Solution for Injection Route of administration : Intravenous

Dosage : The recommended dose of PRAXBIND is 5 g, provided as two separate vials each containing 2. 5 g/50 m. L idarucizumab (see Figure 1). There is limited data to support administration of an additional 5 g Side of PRAXBIND Effect: Thromboembolic Risk; Hypersensitivity Reactions; Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient. Useful links http: //www. ema. europa. eu/docs/en_GB/document_library/EPAR__Public_assessment_report/human/003986/WC 500197465. pdf; http: //www. accessdata. fda. gov/drugsatfda_docs/label/2015/761025 lbl. pdf http: //www. rxlist. com/praxbind-drug. htm; http: //www. accessdata. fda. gov/drugsatfda_docs/label/2015/761025 lbl. pdf :