Peginterferon alfa-2a

Identification

Name
Peginterferon alfa-2a
Accession Number
DB00008
Description

Peginterferon alfa-2a is a form of recombinant interferon used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 3. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) resulting in less use of Peginterferon alfa-2a. Peginterferon alfa-2a is derived from the alfa-2a moeity of recombinant human interferon and acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Use of Peginterferon alfa-2a is associated with a wide range of severe adverse effects including the aggravation and development of endocrine and autoimmune disorders, retinopathies, cardiovascular and neuropsychiatric complications, and increased risk of hepatic decompensation in patients with cirrhosis. The use of Peginterferon alfa-2a has largely declined since newer interferon-free antiviral therapies have been developed.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) no longer recommend Peginterferon alfa-2a for the treatment of Hepatitis C 1. Peginterferon alfa-2a was used alongside Ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 2.

Peginterferon alfa-2a is available as a fixed dose injector (tradename Pegasys) used for the treatment of chronic Hepatitis C. Approved in 2002 by the FDA, Pegasys is indicated for the treatment of HCV with Ribavirin or other antiviral drugs Label. When combined together, Peginterferon alfa-2a and Ribavirin have been shown to achieve a SVR between 36% for genotype 1 and 59% for genotypes 2-6 after 48 weeks of treatment.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
Protein Structure
Db00008
Protein Chemical Formula
Not Available
Protein Average Weight
60000.0 Da
Sequences
>Peginterferon alfa-2a sequence
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
Download FASTA Format
Synonyms
  • PEG-IFN alfa-2A
  • PEG-Interferon alfa-2A
  • Peginterferon alfa-2a
  • Pegylated Interfeaon alfa-2A
  • Pegylated interferon alfa-2a
  • Pegylated interferon alpha-2a
  • Pegylated-interferon alfa 2a
External IDs
  • RO 25-8310/000
  • RO-25-8310/000
  • RO-258310000

Pharmacology

Indication

Peginterferon alfa-2a is indicated for the treatment of HCV in combination with other antiviral drugs in patients over 5 years of age with compensated liver disease Label. May be used as a monotherapy in patients with contraindications to or significant intolerance to other anti-viral therapies.

Peginterferon alfa-2a is also indicated as a monotherapy for adult patients with HBeAg positive and HBeAg negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation Label.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Peginterferon alfa-2a induces the body's innate antiviral response Label.

Mechanism of action

Peginterferon alfa-2a is derived from recombinant human interferon's alfa-2a moeity Label. It binds to and activates human type 1 interferon receptors causing them to dimerize. This activates the JAK/STAT pathway. Activation of the JAK/STAT pathway increases expression of multiple genes in multiple tissues involved in the innate antiviral response.

TargetActionsOrganism
AInterferon alpha/beta receptor 2
agonist
Humans
AInterferon alpha/beta receptor 1
agonist
Humans
Absorption

Peginterferon alfa-2a reaches peak plasma concentration 72-96 hours after subcutaneous administration Label. Trough concentrations at week 48 are approximately 2 fold higher than week 1. The peak to trough ratio at week 48 is 2.

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

The mean terminal half-life of peginterferon alfa-2a is 164 in a range of 84-353 hours Label.

Clearance

The mean systemic clearance of peginterferon alfa-2a is 94 milliliters per hour Label.

Adverse Effects
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Toxicity

Peginterferon alfa-2a may manifest neuropsychiatric complications include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose Label. Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed in patients using Peginterferon alfa-2a. Peginterferon alfa-2a may produce myelosuppression as well as the development or aggravation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. Peginterferon alfa-2a causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with Peginterferon alfa-2a. Peginterferon alfa-2a may decrease or produce loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment. Peginterferon mayy be related to increased ischemic and hemorrhagic cerebrovascular events. Patients with cirrhosis on Peginterferon alfa-2a are at risk of hepatic decompensation. Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis may be induced or aggravated by Peginterferon alfa-2a. Serious and severe infections (bacterial, viral, or fungal) have been reported during treatment with Peginterferon alfa-2a. Ulcerative and hemorrhagic/ischemic colitis have been observed within 12 weeks of starting Peginterferon alfa-2a treatment. Pancreatitis and peripheral nephropathy have also been reported. Peginterferon alfa-2a is associated with growth inhibition in pediatric patients. Use of Peginterferon alfa-2a while pregant may result in delopmental abnormalities or death of the fetus.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Interferon lambda-3---(C;T) / (G;G) / (G;T) / (T;T)C > TEffect Directly StudiedPatients with this genotype in IFNL3 have a reduced likelihood of achieving sustained virologic response to peginterferon alfa-2a therapy.Details

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
AbataceptThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2a.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Peginterferon alfa-2a.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Peginterferon alfa-2a.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Peginterferon alfa-2a.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Peginterferon alfa-2a.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Peginterferon alfa-2a.
AdalimumabThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Adalimumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Peginterferon alfa-2a.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Peginterferon alfa-2a.
Additional Data Available
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  • Severity
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Food Interactions
  • Drink plenty of fluids.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PegasysSolution180 mcgSubcutaneousHoffmann La Roche2003-08-142017-07-27Canada flag
PegasysInjection, solution180 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution135 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution180 ug/0.5mLSubcutaneousGenentech, Inc.2011-03-29Not applicableUS flag
PegasysInjection, solution135 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution180 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution135 ug/0.5mLSubcutaneousGenentech, Inc.2011-11-012019-01-31US flag
PegasysInjection, solution180 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution135 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
PegasysInjection, solution135 μgSubcutaneousRoche Registration Gmb H2002-06-20Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
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    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
    Available for Purchase

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

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Pegasys RbvPeginterferon alfa-2a (180 mcg) + Ribavirin (200 mg)Solution; TabletOral; SubcutaneousHoffmann La Roche2004-05-262018-07-10Canada flag
Pegasys RbvPeginterferon alfa-2a (180 mcg) + Ribavirin (200 mg)Solution; TabletOral; SubcutaneousHoffmann La Roche2004-05-262018-07-10Canada flag

Categories

ATC Codes
L03AB11 — Peginterferon alfa-2aL03AB61 — Peginterferon alfa-2a, combinations
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
Q46947FE7K
CAS number
198153-51-4

References

General References
  1. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432]
  2. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348]
  3. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
UniProt
P01563
Genbank
J00207
PubChem Substance
46504860
RxNav
120608
ChEMBL
CHEMBL1201560
Therapeutic Targets Database
DAP001278
PharmGKB
PA164749390
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Peginterferon_alfa-2a
AHFS Codes
  • 08:18.20 — Interferons
FDA label
Download (1.13 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentViral Hepatitis B1
4CompletedNot AvailableHepatitis B Chronic Infection1
4CompletedBasic ScienceChronic Hepatitis C Virus (HCV) Infection / Liver Diseases / Virus Diseases1
4CompletedDiagnosticChronic Hepatitis C Virus (HCV) Infection1
4CompletedPreventionHepatitis C Viral Infection / Transplantation, Liver1
4CompletedTreatmentAnemia1
4CompletedTreatmentAntiviral Agents / Chronic Liver Diseases (CLD) / Hepatitis C Virus (HCV) Infection / Therapeutic Uses / Virus Hepatitis1
4CompletedTreatmentAsian Americans / Chronic Hepatitis C Virus (HCV) Infection / Novel Genotypes / Treatments1
4CompletedTreatmentChronic Hepatitis C Genotype 11
4CompletedTreatmentChronic Hepatitis C Genotype 1 / Chronic Hepatitis C, Genotype 11

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous135 μg
Injection, solutionSubcutaneous135 MCG
Injection, solutionSubcutaneous135 ug/0.5mL
Injection, solutionSubcutaneous180 μg
Injection, solutionSubcutaneous180 mcg/ml
Injection, solutionSubcutaneous180 ug/1mL
Injection, solutionSubcutaneous180 MCG
Injection, solutionSubcutaneous180 ug/0.5mL
Injection, solutionSubcutaneous90 μg
SolutionSubcutaneous180 mcg
Injection, solutionSubcutaneous135 mcg/0.5ml
Injection, solutionSubcutaneous180 mcg/0.5ml
Solution; tabletOral; Subcutaneous
Prices
Unit descriptionCostUnit
Pegasys (1 Kit = Four 180 mcg/ml Vials Prefilled Syringes) Box2634.53USD box
Pegasys 180 mcg/0.5 ml conv.pk2533.2USD each
Pegasys 180 mcg/ml vial642.64USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2172664No2000-10-032016-03-26Canada flag
CA2203480No2009-06-302017-04-23Canada flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °CBeldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
isoelectric point5.99Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Yano H, Ogasawara S, Momosaki S, Akiba J, Kojiro S, Fukahori S, Ishizaki H, Kuratomi K, Basaki Y, Oie S, Kuwano M, Kojiro M: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 2006 Oct;26(8):964-75. [PubMed:16953837]
  3. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Yano H, Ogasawara S, Momosaki S, Akiba J, Kojiro S, Fukahori S, Ishizaki H, Kuratomi K, Basaki Y, Oie S, Kuwano M, Kojiro M: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 2006 Oct;26(8):964-75. [PubMed:16953837]
  3. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Begre S, von Bardeleben U, Ladewig D, Jaquet-Rochat S, Cosendai-Savary L, Golay KP, Kosel M, Baumann P, Eap CB: Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers. J Clin Psychopharmacol. 2002 Apr;22(2):211-5. [PubMed:11910269]
  2. Peg-interferon FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on November 27, 2020 08:19

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