Interferon Alfa-2a, Recombinant

Identification

Name
Interferon Alfa-2a, Recombinant
Accession Number
DB00034  (BTD00095, BTD00012, BIOD00095, BIOD00012, DB00037)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Interferons
Description

Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences.

Protein structure
Db00034
Protein chemical formula
C860H1353N227O255S9
Protein average weight
19241.1 Da
Sequences
>DB00034 sequence
CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
Download FASTA Format
Synonyms
  • Interferon alfa-2a
  • Interferon alfa-2a (recombinant)
  • Interferon alfa-2a, recombinant
  • Interferon alfa-2a,recombinant
  • Interferon alpha-2a
  • Interferon-alfa-2a
  • Recombinant human interferon alfa-2a
  • Recombinant human interferon-alfa-2a
  • rIFN-alpha-2a
  • SH-polypeptide-46
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Roferon A Soln Inj 6 MillionLiquid6000000 unitIntramuscular; SubcutaneousHoffmann La Roche1989-12-311997-08-26Canada
Roferon A Sterile Pws 18m Unit/vialPowder, for solution18000000 unitIntramuscular; SubcutaneousHoffmann La Roche1991-12-311996-09-30Canada
Roferon A Sterile Pws 3m Unit/vialPowder, for solution3000000 unitIntramuscular; SubcutaneousHoffmann La Roche1991-12-311996-09-30Canada
Roferon A Sterile Pws 9m Unit/vialPowder, for solution9000000 unitIntramuscular; SubcutaneousHoffmann La Roche1991-12-311996-09-30Canada
Roferon-A Solution Inj. 9million I.U./0.9mlSolution9000000 unitIntramuscular; SubcutaneousHoffmann La Roche1993-12-311997-08-26Canada
Roferon-A Sol Inj 3million Iu/vialLiquid3000000 unitIntramuscular; SubcutaneousHoffmann La Roche1989-12-311997-08-25Canada
Roferon-A Soln-liq Im Sc 4.5million I.u/mlLiquid4.5 mIntramuscular; SubcutaneousHoffmann La Roche1997-04-251999-11-02Canada
Roferon-A Soln-liq Im Sc 9million I.U./mlSolution9 mIntramuscular; SubcutaneousHoffmann La Roche1997-04-292004-11-01Canada
Roferon-A Solution 18 Million I.U./3mlSolution18 mIntramuscular; SubcutaneousHoffmann La Roche1997-01-152005-07-14Canada
Roferon-A Solution 3 Million I.U./mlSolution3 mIntramuscular; SubcutaneousHoffmann La Roche1997-02-252005-07-14Canada
International/Other Brands
Roferon A (Hoffmann-La Roche Inc) / Veldona (Amarillo Biosciences)
Categories
UNII
47RRR83SK7
CAS number
76543-88-9

Pharmacology

Indication

For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection.

Structured Indications
Not Available
Pharmacodynamics

Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.

Mechanism of action

Interferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.

TargetActionsOrganism
AInterferon alpha/beta receptor 1Not AvailableHuman
AInterferon alpha/beta receptor 2Not AvailableHuman
Absorption

Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

Volume of distribution
  • 0.223 to 0.748 L/kg [healthy people]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Alpha-interferons are totally filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption, rendering a negligible reappearance of intact alfa interferon in the systemic circulation.

Half life

The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours).

Clearance
  • 2.14 - 3.62 mL/min/kg [healthy]
Toxicity

Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AldesleukinThe risk or severity of adverse effects can be increased when Interferon Alfa-2a, Recombinant is combined with Aldesleukin.Approved
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon Alfa-2a, Recombinant.Experimental
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Interferon Alfa-2a, Recombinant.Approved
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Interferon Alfa-2a, Recombinant.Approved
MethadoneThe serum concentration of Methadone can be increased when it is combined with Interferon Alfa-2a, Recombinant.Approved
RibavirinThe risk or severity of adverse effects can be increased when Interferon Alfa-2a, Recombinant is combined with Ribavirin.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Interferon Alfa-2a, Recombinant.Approved
ZidovudineThe risk or severity of adverse effects can be increased when Interferon Alfa-2a, Recombinant is combined with Zidovudine.Approved
Food Interactions
  • Avoid alcohol.

References

General References
Not Available
External Links
UniProt
P01563
Genbank
J00207
PubChem Substance
46506712
Therapeutic Targets Database
DAP000801
PharmGKB
PA164779048
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
L03AB04 — Interferon alfa-2a
FDA label
Download (204 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAnus Neoplasms / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)2
1, 2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
2CompletedTreatmentAdenocarcinomas / Carcinoma NOS / Hypernephroid / Nephroid Carcinoma / Renal Cell / Renal Cell Adenocarcinoma1
2CompletedTreatmentBehcet's Syndrome / Mucocutaneous Ulceration1
2CompletedTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentHepatitis C, Chronic1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Papillomatosis1
2CompletedTreatmentLeukemias / Malignant Lymphomas / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMetastatic Melanoma1
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentRenal Cell Adenocarcinoma2
2TerminatedTreatmentCancer, Breast / Metastatic Cancers1
2TerminatedTreatmentCancers1
3CompletedTreatmentChronic Hepatitis C Infection1
3CompletedTreatmentRenal Cell Adenocarcinoma1
3RecruitingTreatmentBeh├žet's Disease / Uveitis1
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / End Stage Renal Disease (ESRD)1
Not AvailableCompletedNot AvailableRenal Cell Adenocarcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
LiquidIntramuscular; Subcutaneous6000000 unit
Powder, for solutionIntramuscular; Subcutaneous18000000 unit
Powder, for solutionIntramuscular; Subcutaneous3000000 unit
Powder, for solutionIntramuscular; Subcutaneous9000000 unit
SolutionIntramuscular; Subcutaneous9000000 unit
LiquidIntramuscular; Subcutaneous3000000 unit
LiquidIntramuscular; Subcutaneous4.5 m
SolutionIntramuscular; Subcutaneous9 m
SolutionIntramuscular; Subcutaneous18 m
SolutionIntramuscular; Subcutaneous3 m
SolutionIntramuscular; Subcutaneous6 m
SolutionIntramuscular; Subcutaneous36000000 unit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2172664No2000-10-032016-03-26Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubility100 mg/mlNot Available
hydrophobicity-0.336Not Available
isoelectric point5.99Not 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
Yes
General Function
Type i interferon receptor activity
Specific Function
Associates with IFNAR2 to form the type I interferon receptor. Receptor for interferons alpha and beta. Binding to type I IFNs triggers tyrosine phosphorylation of a number of proteins including JA...
Gene Name
IFNAR1
Uniprot ID
P17181
Uniprot Name
Interferon alpha/beta receptor 1
Molecular Weight
63524.81 Da
References
  1. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717]
  2. Cironi P, Swinburne IA, Silver PA: Enhancement of cell type specificity by quantitative modulation of a chimeric ligand. J Biol Chem. 2008 Mar 28;283(13):8469-76. doi: 10.1074/jbc.M708502200. Epub 2008 Jan 29. [PubMed:18230610]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Type i interferon receptor activity
Specific Function
Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are direc...
Gene Name
IFNAR2
Uniprot ID
P48551
Uniprot Name
Interferon alpha/beta receptor 2
Molecular Weight
57758.24 Da
References
  1. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717]
  2. Cironi P, Swinburne IA, Silver PA: Enhancement of cell type specificity by quantitative modulation of a chimeric ligand. J Biol Chem. 2008 Mar 28;283(13):8469-76. doi: 10.1074/jbc.M708502200. Epub 2008 Jan 29. [PubMed:18230610]

Drug created on June 13, 2005 07:24 / Updated on November 06, 2017 06:43