Coagulation factor VIIa Recombinant Human

Identification

Name
Coagulation factor VIIa Recombinant Human
Accession Number
DB00036  (BTD00006, BIOD00006)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Blood factors
Description

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.

Protein structure
Db00036
Protein chemical formula
C1972H3076N560O597S28
Protein average weight
45079.1 Da
Sequences
>DB00036 sequence
ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGS
CKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL
LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGG
TLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTN
HDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVL
NVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTG
IVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP
Download FASTA Format
Synonyms
  • Coagulation factor VIIa
  • Coagulation factor VIIa (recombinant)
  • Eptacog alfa
  • Eptacog alfa (activated)
  • rFVIIa
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NiastasePowder, for solution1.2 mgIntravenousNovo Nordisk1999-08-052013-07-22Canada
NiastasePowder, for solution2.4 mgIntravenousNovo Nordisk1999-08-052013-07-22Canada
NiastasePowder, for solution4.8 mgIntravenousNovo Nordisk1999-08-052013-07-22Canada
Niastase RTKit; Powder, for solution1 mgIntravenousNovo Nordisk2015-05-05Not applicableCanada
Niastase RTKit; Powder, for solution2 mgIntravenousNovo Nordisk2010-08-05Not applicableCanada
Niastase RTKit; Powder, for solution1 mgIntravenousNovo Nordisk2010-08-25Not applicableCanada
Niastase RTKit; Powder, for solution8 mgIntravenousNovo NordiskNot applicableNot applicableCanada
Niastase RTKit; Powder, for solution5 mgIntravenousNovo Nordisk2010-08-25Not applicableCanada
Niastase RTKit; Powder, for solution2 mgIntravenousNovo Nordisk2015-05-05Not applicableCanada
Niastase RTKit; Powder, for solution5 mgIntravenousNovo Nordisk2015-05-05Not applicableCanada
International/Other Brands
NovoSeven (Novo Nordisk)
Categories
UNII
AC71R787OV
CAS number
102786-61-8

Pharmacology

Indication

For treatment of hemorrhagic complications in hemophilia A and B

Structured Indications
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.

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.

TargetActionsOrganism
UCoagulation factor XNot AvailableHuman
UTissue factorNot AvailableHuman
USerine protease hepsinNot AvailableHuman
UTissue factor pathway inhibitorNot AvailableHuman
UVitamin K-dependent gamma-carboxylaseNot AvailableHuman
UCoagulation factor VIINot AvailableHuman
Absorption
Not Available
Volume of distribution
  • 121 ± 30 mL/kg [adults]
  • 153 ± 29 mL/kg [children]
  • 280 to 290 mL/kg [congenital Factor VII deficiency]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
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]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. 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:2155]
  2. 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:15328151]
  3. Kenet G, Walden R, Eldad A, Martinowitz U: Treatment of traumatic bleeding with recombinant factor VIIa. Lancet. 1999 Nov 27;354(9193):1879. [PubMed:10584732]
  4. 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:16418464]
  5. 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:15728810]
External Links
UniProt
P08709
Genbank
M13232
KEGG Drug
D00172
KEGG Compound
C03378
PubChem Substance
46507544
PharmGKB
PA164748389
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Factor_VII
ATC Codes
B02BD08 — Eptacog alfa (activated)
AHFS Codes
  • 20:28.16 — Hemostatics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHemophilia1
1CompletedDiagnosticCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B With Inhibitors1
1CompletedTreatmentCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B / Haemophilia B With Inhibitors / Hemophilia A1
1CompletedTreatmentHealthy Volunteers / Hemostasis1
1TerminatedTreatmentHealthy Volunteers / Hemostasis1
1TerminatedTreatmentIntracranial Hemorrhages1
1WithdrawnTreatmentCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B / Haemophilia B With Inhibitors / Healthy Volunteers / Hemophilia A1
2Active Not RecruitingTreatmentStrokes1
2CompletedTreatmentAcquired Bleeding Disorder / Dengue Hemorrhagic Fever1
2CompletedTreatmentAcquired Bleeding Disorder / Fusion of Spine (Disease)1
2CompletedTreatmentAcquired Bleeding Disorder / Intracerebral Hemorrhage1
2CompletedTreatmentCongenital Hematological Disorder / Haemophilia B / Hemophilia A1
2CompletedTreatmentIntracerebral Hemorrhage1
2RecruitingTreatmentCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B With Inhibitors1
2Unknown StatusTreatmentHemophilia A With Inhibitors1
2, 3CompletedTreatmentHemophilia A, Hemophilia B1
2, 3RecruitingTreatmentHemophilia A With Inhibitors / Hemophilia B With Inhibitors1
3Active Not RecruitingTreatmentHemophilia A1
3CompletedNot AvailableHemophilia A1
3CompletedTreatmentAcquired Bleeding Disorder / Intracerebral Hemorrhage1
3CompletedTreatmentCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B With Inhibitors1
3CompletedTreatmentHemophilia A With Inhibitors / Hemophilia B With Inhibitors1
3CompletedTreatmentMinor burns1
3RecruitingTreatmentHemophilia1
3TerminatedTreatmentAcquired Bleeding Disorder / Traumas1
4CompletedTreatmentCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B With Inhibitors1
4CompletedTreatmentHemophilia A1
4CompletedTreatmentPostpartum Hemorrhage1
Not AvailableCompletedNot AvailableAcquired Bleeding Disorder / Acquired Haemophilia / Congenital FVII Deficiency / Congenital Hematological Disorder / Glanzmann's Disease1
Not AvailableCompletedNot AvailableCongenital Hematological Disorder / Glanzmann's Disease1
Not AvailableCompletedNot AvailableCongenital Hematological Disorder / Haemophilia A With Inhibitors / Haemophilia B With Inhibitors6
Not AvailableCompletedNot AvailableCongenital Hematological Disorder / Haemophilia B / Hemophilia A1
Not AvailableCompletedNot AvailableCongenital Factor VII deficiency1
Not AvailableCompletedTreatmentSevere Hemophilia A With an Inhibitor1
Not AvailableRecruitingNot AvailableMassive Blood Loss / Massive Blood Transfusion; Thrombocytopenia / Massive Hemorrhage1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous1.2 mg
Powder, for solutionIntravenous2.4 mg
Powder, for solutionIntravenous4.8 mg
Kit; powder, for solutionIntravenous1 mg
Kit; powder, for solutionIntravenous2 mg
Kit; powder, for solutionIntravenous5 mg
Kit; powder, for solutionIntravenous8 mg
Injection, powder, for solutionIntravenous100 KIU
Injection, powder, for solutionIntravenous250 KIU
Injection, powder, for solutionIntravenous400 KIU
Injection, powder, for solutionIntravenous50 KIU
Kit
Prices
Unit descriptionCostUnit
Novoseven 1200 mcg vial1.64USD vial
Novoseven 2400 mcg vial1.64USD vial
Novoseven 4800 mcg vial1.64USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)58 °CPetersen, L.C. et al., Eur. J. Biochem 261: 124-129 (1999)
hydrophobicity-0.311Not Available
isoelectric point6.09Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Malinvaud G: [Reflections on the use of PPSB fraction (Prothrombin-proconvertin-Stuart factor-antihemophilic factor B)]. Transfusion (Paris). 1966;9(3):245-54. [PubMed:5969560]
  2. BLATRIX C, SOULIER JP: [Preparation of a fraction rich in prothrombin, proconvertin, Stuart factor and antihemophilic factor B (P.P.B. fraction)]. Pathol Biol (Paris). 1959 Dec;7:2477-86. [PubMed:13801371]
  3. HERMANSKY F, VITEK J: The role of proconvertin and Stuart factor in the inactivation of tissue thromboplastin by serum. Experientia. 1960 Oct 15;16:455-6. [PubMed:13713641]
  4. GAERTNER H, CAEN J: [FUNCTIONAL RELATION BETWEEN ERYTHROPLASTIN (ERYTHROCYTE COAGULANT FACTOR) AND PLASMA FACTORS: PROACCELERIN (V), PROCONVERTIN (VII) AND STUART FACTOR(X)]. Acta Physiol Pol. 1964 Mar-Apr;15:237-43. [PubMed:14227143]
  5. DIDISHEIM P, LOEB J, BLATRIX C, SOULIER JP: Preparation of a human plasma fraction rich in prothrombin, proconvertin, Stuart factor, and PTC and a study of its activity and toxicity in rabbits and man. J Lab Clin Med. 1959 Feb;53(2):322-30. [PubMed:13621053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protease binding
Specific Function
Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemos...
Gene Name
F3
Uniprot ID
P13726
Uniprot Name
Tissue factor
Molecular Weight
33067.3 Da
References
  1. HERMANSKY F, VITEK J: The role of proconvertin and Stuart factor in the inactivation of tissue thromboplastin by serum. Experientia. 1960 Oct 15;16:455-6. [PubMed:13713641]
  2. Rogers KS, Barton CL, Benson PA, Green RA: Effects of single-dose L-asparaginase on coagulation values in healthy dogs and dogs with lymphoma. Am J Vet Res. 1992 Apr;53(4):580-4. [PubMed:1586032]
  3. Christensen NJ: Measurements of some blood clotting factors using a centrifugal analyser (Multistat III). Scand J Clin Lab Invest. 1983 Oct;43(6):521-6. [PubMed:6658368]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type peptidase activity
Specific Function
Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.
Gene Name
HPN
Uniprot ID
P05981
Uniprot Name
Serine protease hepsin
Molecular Weight
45011.01 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action...
Gene Name
TFPI
Uniprot ID
P10646
Uniprot Name
Tissue factor pathway inhibitor
Molecular Weight
35014.835 Da
References
  1. Mine S, Yamazaki T, Miyata T, Hara S, Kato H: Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor. Biochemistry. 2002 Jan 8;41(1):78-85. [PubMed:11772005]
  2. Narita M, Bu G, Olins GM, Higuchi DA, Herz J, Broze GJ Jr, Schwartz AL: Two receptor systems are involved in the plasma clearance of tissue factor pathway inhibitor in vivo. J Biol Chem. 1995 Oct 20;270(42):24800-4. [PubMed:7559599]
  3. Stassens P, Bergum PW, Gansemans Y, Jespers L, Laroche Y, Huang S, Maki S, Messens J, Lauwereys M, Cappello M, Hotez PJ, Lasters I, Vlasuk GP: Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2149-54. [PubMed:8700900]
  4. Lee AY, Vlasuk GP: Recombinant nematode anticoagulant protein c2 and other inhibitors targeting blood coagulation factor VIIa/tissue factor. J Intern Med. 2003 Oct;254(4):313-21. [PubMed:12974870]
  5. Hansen CB, Pyke C, Petersen LC, Rao LV: Tissue factor-mediated endocytosis, recycling, and degradation of factor VIIa by a clathrin-independent mechanism not requiring the cytoplasmic domain of tissue factor. Blood. 2001 Mar 15;97(6):1712-20. [PubMed:11238112]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Gamma-glutamyl carboxylase activity
Specific Function
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vit...
Gene Name
GGCX
Uniprot ID
P38435
Uniprot Name
Vitamin K-dependent gamma-carboxylase
Molecular Weight
87560.065 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bouwman CA, Van Dam E, Fase KM, Koppe JG, Seinen W, Thijssen HH, Vermeer C, Van den Berg M: Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'-hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female WAG/Rij-rats. Chemosphere. 1999 Feb;38(3):489-505. [PubMed:10901669]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type peptidase activity
Specific Function
Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, o...
Gene Name
F7
Uniprot ID
P08709
Uniprot Name
Coagulation factor VII
Molecular Weight
51593.465 Da
References
  1. Perera L, Darden TA, Pedersen LG: Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association. Biophys J. 1999 Jul;77(1):99-113. [PubMed:10388743]
  2. Shapiro A: Inhibitor treatment: state of the art. Semin Hematol. 2001 Oct;38(4 Suppl 12):26-34. [PubMed:11735107]
  3. Shapiro A: Inhibitor treatment: state of the art. Dis Mon. 2003 Jan;49(1):22-38. [PubMed:12525826]
  4. Siddiqui MA, Scott LJ: Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs. 2005;65(8):1161-77. [PubMed:15907148]
  5. Rizoli SB, Chughtai T: The emerging role of recombinant activated Factor VII (rFVIIa) in the treatment of blunt traumatic haemorrhage. Expert Opin Biol Ther. 2006 Jan;6(1):73-81. [PubMed:16370916]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33