Coagulation factor VIIa Drugbank ID : DB00036 Protein Chemical formula : C1972H3076N560O597S28 Protein average weight : 45079.1000

Description : Indication : Pharmacodynamics : Recombinant human coagulation Factor VIIa (rFVIIa), intended for promoting hemostasis by activating the extrinsic pathway of the coagulation cascade. NovoSeven is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues. Cloned and expressed in hamster kidney cells, the protein is catalytically active in a two-chain form. Indication : For treatment of hemorrhagic complications in hemophilia A and B Pharmacodynamics : Used in the treatment of bleeding episodes in hemophilia A or B. NovoSeven is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local clotting.

Volume of distribution : Mechanism of action : NovoSeven activates the coagulation or clotting cascade by cleaving Factor IX and Factor X, which activates them and then leads to activation of thrombin and fibrin. Volume of distribution : 121 ± 30 mL/kg [adults] 153 ± 29 mL/kg [children] 280 to 290 mL/kg [congenital Factor VII deficiency]

Clearance : 33 - 37 mL/h x kg [healthy] 1375 +/- 396 mL/hr [severe hemophilia A male children] 57.3 +/- 9.5 mL/hr/kg [severe hemophilia A male children] 2767 +/- 385 mL/hr [severe hemophilia A men] 37.6 +/- 13.1 mL/hr/kg [severe hemophilia A men]

Targets : Affected organisms : Coagulation factor X,Serine protease hepsin,Tissue factor pathway inhibitor,Vitamin K-dependent gamma-carboxylase,Coagulation factor VII,Tissue factor Affected organisms : Humans and other mammals .

Categories : Sequence : Coagulants and Thrombotic Agents ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP

Brands : NovoSeven Company : Novo Nordisk Description : NovoSeven®is recombinant human coagulation Factor VIIa (rFVIIa), intended for promoting hemostasis by activating the extrinsic pathway of the coagulation cascade. NovoSeven (coagulation factor viia recombinant) is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues (MW 50 K Dalton). NovoSeven (coagulation factor viia recombinant) is structurally similar to human plasma-derived Factor VIIa. The gene for human Factor VII is cloned and expressed in baby hamster kidney cells (BHK cells). Recombinant FVII is secreted into the culture media (containing newborn calf serum) in its single-chain form and then proteolytically converted by autocatalysis to the active two-chain form, rFVIIa, during a chromatographic purification process. The purification process has been demonstrated to remove exogenous viruses (MuLV, SV40, Pox virus, Reovirus, BEV, IBR virus). No human serum or other proteins are used in the production or formulation of NovoSeven.

Used for/Prescribed for : Treatment of bleeding and prevention of bleeding for surgeries and procedures in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and people with Glanzmann’s thrombasthenia who have a decreased or absent response to platelet transfusions Treatment of bleeding and prevention of bleeding for surgeries and procedures in adults with acquired hemophilia Formulation : each vial contains approximately 0. 6 mg/mL NovoSeven (coagulation factor viia recombinant) (corresponding to 600 μg/mL). The reconstituted vials have a pH of approximately 5. 5 in sodium chloride (3 mg/mL), calcium chloride dihydrate (1. 5 mg/mL), glycylglycine (1. 3 mg/mL), polysorbate 80 (0. 1 mg/mL), and mannitol (30 mg/mL). NovoSeven (coagulation factor viia recombinant) contains trace amounts of proteins derived from the manufacturing and purification processes such as mouse IgG (maximum of 1. 2 ng/mg), bovine IgG (maximum of 30 ng/mg), and protein from BHK-cells and media (maximum of 19ng/mg). Form : sterile, white lyophilized powder Route of administration : injection

Dosage : For bleeding episodes, the recommended dose of NovoSeven (coagulation factor viia (recombinant)) for hemophilia A or B patients with inhibitors is 90 μg/kg given every two hours by bolus infusion until hemostasis is achieved, or until the treatment has been judged to be inadequate. Doses between 35 and 120 μg/kg have been used successfully in clinical trials for hemophilia A or B patients with inhibitors, and both the dose and administration interval may be adjusted based on the severity of the bleeding and degree of hemostasis achieved. For surgical interventions, an initial dose of 90 μg per kg body weight should be given immediately before the intervention and repeated at 2-hour intervals for the duration of the surgery. For minor surgery, post-surgical dosing by bolus infusion should occur at 2-hour intervals for the first 48 hours and then at 2- to 6-hour intervals until healing has occurred. For major surgery, post-surgical dosing by bolus infusion should occur at 2 hour intervals for 5 days, followed by 4 hour intervals until healing has occurred. Additional bolus doses should be administered if required. The recommended dose range for the treatment of patients with acquired hemophilia is 70-90 μg/kg repeated every 2-3 hours until hemostasis is achieved. The minimum effective dose in acquired hemophilia has not been determined. Contraindication : Hypersensitivity

Side effects : Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bleeding at the injection site; bloody stools; calf or stomach pain, tenderness, or swelling; chest pain; confusion; dizziness; fainting; numbness of an arm or leg; one-sided weakness; shortness of breath; sudden severe headache or vomiting; swelling; uncontrolled bleeding; vision or speech changes; vomiting blood or material that looks like coffee grounds; wheezing. Drug interaction : A total of 3 drugs (11 brand and generic names) are known to interact with Novoseven (coagulation factor viia) among which 2 drug (9 brand and generic names) shows moderate interaction and 1 (2 brand and generic names) shows minor interactiion .

General references : # Blackshear PJ, Holloway PA, Alberti KG: Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. Biochem J. 1975 Sep;150(3):379-87. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/2155 # Roberts HR, Monroe DM, White GC: The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood. 2004 Dec 15;104(13):3858-64. Epub 2004 Aug 24. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15328151 # Kenet G, Walden R, Eldad A, Martinowitz U: Treatment of traumatic bleeding with recombinant factor VIIa. Lancet. 1999 Nov 27;354(9193):1879. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/10584732 # O'Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM: Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006 Jan 18;295(3):293-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16418464 # Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T: Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005 Feb 24;352(8):777-85. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15728810

References : http://www. novosevenrt. com/ http://www. novonordisk. co