Antihemophilic Factor (Recombinant), PEGylated

Identification

Name
Antihemophilic Factor (Recombinant), PEGylated
Accession Number
DB09329
Description

Antihemophilic Factor (Recombinant), PEGylated, was approved by the FDA in December 2016 as the product Adynovate Label.

Antihemophilic Factor (Recombinant), PEGylated, is a recombinant full-length human coagulation factor VIII (2,332 amino acids with a molecular weight (MW) of approximately 280 kDa) covalently conjugated with at least one molecule of polyethylene glycol (MW 20 kDa) Label. It has been created to increase the half-life of factor VIII, which decreases dose frequency and decreases the occurrence of bleeding events 2, 3, Label.

PEGylation is the covalent attachment of a polyethylene glycol polymer, called PEG, to a drug or protein. PEGylation decreases factor VIII clearance and allowing for an increased duration of drug circulation in the plasma 7.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Blood factors
Protein Chemical Formula
Not Available
Protein Average Weight
284.0 Da
Sequences
Not Available
Synonyms
  • Antihemophilic Factor (Recombinant), PEGylated
  • antihemophilic factor (recombinant), PEGylated-aucl
External IDs
  • BAY 94-9027

Pharmacology

Indication

For the management of hemophilia A (congenital factor VIII deficiency) Label, 1. This medication is a human antihemophilic factor indicated in adolescent and adult patients (12 years and older) with hemophilia A (congenital factor VIII deficiency). It is also used for on-demand treatment and control of bleeding and routine prophylaxis of bleeding episodes. It is not indicated for the treatment of von Willebrand disease Label.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

This drug temporarily replaces the missing coagulation factor VIII, required for effective hemostasis in patients with congenital hemophilia A Label.

Hemophilia A patients have a deficiency of factor VIII, resulting in a prolonged, patient plasma clotting time as demonstrated by the activated partial thromboplastin time (aPTT). Treatment with recombinant factor VIII normalizes the aPTT. Hemophilia A is a sex-linked hereditary disorder of blood coagulation caused by decreased levels of Factor VIII activity, resulting in severe bleeding into the joints, muscles or internal organs, spontaneously/as a result of trauma 18, 6.

Mechanism of action

PEG with Factor VIII effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce the susceptibility of this molecule to proteolytic degradation. It is also believed that PEGylation alters the surface charge of the protein that inhibits receptor-mediated clearance 4. This drug reduces binding to the LRP1 receptor, which normally clears factor VIII from the circulation 5, Label.

The plasma levels of Factor VIII are increased with replacement therapy, which allows for a temporary correction of the factor deficiency, thus a correction of the bleeding tendency 18.

TargetActionsOrganism
Avon Willebrand factor
binder
Humans
Absorption

AUC0-Inf [IU·h/dL]:

1642 ± 752 in children aged 12 to <18 years Label 2264 ± 729 in adults ≥18 years Label

Volume of distribution

At steady state: 0.56 ± 0.18 dL/Kg in children aged 12 to <18 years Label 0.43 ± 0.11 dL/kg in adults aged ≥18 years Label

Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

14.69 ± 3.79h for adults aged ≥18 years Label

13.43 ± 4.05 for children 12 to <18 years Label

Clearance

2.27 ± 0.84 for adults ≥18 years Label

3.87 ± 3.31 for children 12 to <18 years Label

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Common adverse reactions reported in ≥1% of subjects in the clinical studies were headache and nausea Label,Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
AbciximabThe therapeutic efficacy of Antihemophilic Factor (Recombinant), PEGylated can be decreased when used in combination with Abciximab.
AcarboseAcarbose may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Antihemophilic Factor (Recombinant), PEGylated can be decreased when used in combination with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidThe therapeutic efficacy of Antihemophilic Factor (Recombinant), PEGylated can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumAclidinium may decrease the excretion rate of Antihemophilic Factor (Recombinant), PEGylated which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdynovateKit; Powder, for solution2000 unitIntravenousShire Pharma Canada Ulc2018-03-06Not applicableCanada flag
AdynovateKit; Powder, for solution1000 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution250 unitIntravenousShire Pharma Canada Ulc2018-03-06Not applicableCanada flag
AdynovateKit; Powder, for solution500 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution1500 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution1000 unitIntravenousShire Pharma Canada Ulc2018-03-06Not applicableCanada flag
AdynovateKit; Powder, for solution750 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution250 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution1500 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
AdynovateKit; Powder, for solution500 unitIntravenousShire Pharma Canada Ulc2018-03-06Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
Not Available
CAS number
1628187-15-4

References

General References
  1. Dunn AL, Ahuja SP, Mullins ES: Real-world experience with use of Antihemophilic Factor (Recombinant), PEGylated for prophylaxis in severe haemophilia A. Haemophilia. 2018 Jan 23. doi: 10.1111/hae.13403. [PubMed:29359417]
  2. Wynn TT, Gumuscu B: Potential role of a new PEGylated recombinant factor VIII for hemophilia A. J Blood Med. 2016 Jun 20;7:121-8. doi: 10.2147/JBM.S82457. eCollection 2016. [PubMed:27382347]
  3. Tiede A, Brand B, Fischer R, Kavakli K, Lentz SR, Matsushita T, Rea C, Knobe K, Viuff D: Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost. 2013 Apr;11(4):670-8. doi: 10.1111/jth.12161. [PubMed:23398640]
  4. Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [PubMed:6424437]
  5. Bovenschen N, van Dijk KW, Havekes LM, Mertens K, van Vlijmen BJ: Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice. Br J Haematol. 2004 Sep;126(5):722-5. doi: 10.1111/j.1365-2141.2004.05093.x. [PubMed:15327526]
  6. Coppola A, Di Capua M, Di Minno MN, Di Palo M, Marrone E, Ierano P, Arturo C, Tufano A, Cerbone AM: Treatment of hemophilia: a review of current advances and ongoing issues. J Blood Med. 2010;1:183-95. doi: 10.2147/JBM.S6885. Epub 2010 Aug 30. [PubMed:22282697]
  7. Adynovate Pro [Link]
  8. Adynovate assessment report EMA [Link]
  9. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients [Link]
  10. Potential role of a new PEGylated recombinant factor VIII for hemophilia A [Link]
  11. Potential role of a new PEGylated recombinant factor VIII for hemophilia A [Link]
  12. PEGylation of a Factor VIII–Phosphatidylinositol Complex: Pharmacokinetics and Immunogenicity in Hemophilia A Mice [Link]
  13. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A [Link]
  14. Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII [Link]
  15. Antihemophilic Factor (Recombinant [Pegylated]) [Link]
  16. EMA label Adate [Link]
  17. F8 gene coagulation factor VIII [Link]
  18. Advate Product Monograph [Link]
PubChem Substance
347910440
RxNav
1741397
AHFS Codes
  • 20:28.16 — Hemostatics
FDA label
Download (474 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentHemophilia A1
3CompletedPreventionHemophilia A1
3CompletedTreatmentHemophilia A2
3RecruitingTreatmentHemophilia A / Novel Coronavirus Infectious Disease (COVID-19)1
2, 3CompletedTreatmentHemophilia A1
1CompletedBasic ScienceHemophilia A2
1CompletedTreatmentHemophilia A1
Not AvailableCompletedNot AvailableHemophilia1
Not AvailableCompletedNot AvailableHemophilia A1
Not AvailableNot Yet RecruitingNot AvailableHemophilia A2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Kit; powder, for solutionIntravenous1000 unit
Kit; powder, for solutionIntravenous1500 unit
Kit; powder, for solutionIntravenous2000 unit
Kit; powder, for solutionIntravenous250 unit
Kit; powder, for solutionIntravenous3000 unit
Kit; powder, for solutionIntravenous500 unit
Kit; powder, for solutionIntravenous750 unit
Injection, powder, lyophilized, for solutionIntravenous500 IU
Injection, powder, lyophilized, for solutionIntravenous1000 IU
Injection, powder, lyophilized, for solutionIntravenous2000 IU
Injection, powder, lyophilized, for solutionIntravenous250 IU
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Protein n-terminus binding
Specific Function
Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surf...
Gene Name
VWF
Uniprot ID
P04275
Uniprot Name
von Willebrand factor
Molecular Weight
309261.83 Da
References
  1. Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [PubMed:6424437]
  2. Tiede A, Brand B, Fischer R, Kavakli K, Lentz SR, Matsushita T, Rea C, Knobe K, Viuff D: Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost. 2013 Apr;11(4):670-8. doi: 10.1111/jth.12161. [PubMed:23398640]
  3. F8 gene coagulation factor VIII [Link]
  4. Adynovate FDA label [File]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein n-terminus binding
Specific Function
Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surf...
Gene Name
VWF
Uniprot ID
P04275
Uniprot Name
von Willebrand factor
Molecular Weight
309261.83 Da
References
  1. Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [PubMed:6424437]
  2. Wynn TT, Gumuscu B: Potential role of a new PEGylated recombinant factor VIII for hemophilia A. J Blood Med. 2016 Jun 20;7:121-8. doi: 10.2147/JBM.S82457. eCollection 2016. [PubMed:27382347]
  3. Adynovate FDA label [File]

Drug created on November 18, 2015 09:20 / Updated on October 26, 2020 22:41

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