Peginterferon alfa-2a

Identification

Summary

Peginterferon alfa-2a is a modified form of recombinant human interferon used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses.

Brand Names

Pegasys

Generic Name

Peginterferon alfa-2a

DrugBank Accession Number

DB00008

Background

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

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

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

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.

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to treat	Chronic hepatitis c virus (hcv) infection		••••••••••••	•••••	••••••••••• ••••• •••••••	•••••••••
Treatment of	Chronic hepatitis c virus (hcv) infection		••••••••••••	•••••	••••••••••• ••••• •••••••• •••••••••••••••• •• ••••••••••• •• ••••• •••••••	•••••••••
Used in combination to treat	Chronic hepatitis c virus (hcv) infection	Regimen in combination with: Ribavirin (DB00811)	••••••••••••	•••••••••	••••••••••• ••••• •••••••	•••••••••
Treatment of	Hbeag positive chronic hepatitis b		••••••••••••	•••••••••	•••••••••• •• ••••• ••••••• •••••••••••••••• •••••• ••••• •••••••••••• •••••••••••••	•••••••••
Treatment of	Hepatitis b chronic infection		••••••••••••	•••••	••••••••••• ••••• •••••••• ••••• •••••••••••	•••••••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

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.

Target	Actions	Organism
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

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

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.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Interferon lambda-3	---	(T;T) / (C;T) / (G;G) / (G;T)	C > T	Effect Directly Studied	Patients 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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abatacept	The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon alfa-2a.
Acenocoumarol	The metabolism of Acenocoumarol can be decreased when combined with Peginterferon alfa-2a.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Peginterferon alfa-2a.
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Peginterferon alfa-2a.

Food Interactions

Drink plenty of fluids.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Pegasys	Solution	180 mcg / 0.5 mL	Subcutaneous	Zr Pharma& Gmbh	2003-08-14	Not applicable
Pegasys	Injection, solution	180 μg	Subcutaneous	Zr Pharma& Gmb H	2016-09-08	Not applicable
Pegasys	Injection, solution	180 ug/1mL	Subcutaneous	Genentech, Inc.	2002-10-16	2025-06-30
Pegasys	Injection, solution	135 μg	Subcutaneous	Zr Pharma& Gmb H	2016-09-08	Not applicable
Pegasys	Injection, solution	180 μg	Subcutaneous	Zr Pharma& Gmb H	2016-09-08	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Pegasys Rbv	Peginterferon alfa-2a (180 mcg / 0.5 mL) + Ribavirin (200 mg / tab)	Solution; Tablet	Oral; Subcutaneous	Hoffmann La Roche	2004-05-26	2018-07-10
Pegasys Rbv	Peginterferon alfa-2a (180 mcg / mL) + Ribavirin (200 mg / tab)	Solution; Tablet	Oral; Subcutaneous	Hoffmann La Roche	2004-05-26	2018-07-10

Chemical Identifiers

UNII: Q46947FE7K
CAS number: 198153-51-4

References

General References

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. [Article]
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. [Article]
American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]

External Links

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

FDA label

Download (1.13 MB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Viral Hepatitis B	1
4	Completed	Not Available	Chronic Hepatitis B Infection	1
4	Completed	Basic Science	Chronic Hepatitis C Virus (HCV) Infection / Liver Disease / Viral Disease	1
4	Completed	Diagnostic	Chronic Hepatitis C Virus (HCV) Infection	1
4	Completed	Prevention	Chronic Hepatitis B Infection	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

F Hoffmann La Roche Ltd.
F Hoffmann-La Roche Ltd.

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous
Injection, solution	Subcutaneous	135 μg
Injection, solution	Subcutaneous	135 ug/0.5mL
Injection, solution	Subcutaneous	135 MCG
Injection, solution	Subcutaneous	180 μg
Injection, solution	Subcutaneous	180 ug/1mL
Injection, solution	Subcutaneous	180 mcg/ml
Injection, solution	Subcutaneous	180 ug/0.5mL
Injection, solution	Subcutaneous	180 MCG
Injection, solution	Subcutaneous	90 μg
Solution	Subcutaneous	0.135 mg
Solution	Subcutaneous	180 mcg / mL
Solution	Subcutaneous	180 mcg / 0.5 mL
Injection, solution	Subcutaneous
Injection	Subcutaneous	135 mcg/0.5ml
Injection	Subcutaneous	180 mcg/0.5ml
Solution; tablet	Oral; Subcutaneous
Injection, solution	Subcutaneous	135 mcg/0.5ml
Injection, solution	Subcutaneous	180 mcg/0.5ml

Prices

Unit description	Cost	Unit
Pegasys (1 Kit = Four 180 mcg/ml Vials Prefilled Syringes) Box	2634.53USD	box
Pegasys 180 mcg/0.5 ml conv.pk	2533.2USD	each
Pegasys 180 mcg/ml vial	642.64USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
CA2172664	No	2000-10-03	2016-03-26
CA2203480	No	2009-06-30	2017-04-23

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	61 °C	Beldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
isoelectric point	5.99	Not Available

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Interferon alpha/beta receptor 2

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

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. [Article]
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. [Article]
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. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Details2. Interferon alpha/beta receptor 1

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

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. [Article]
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. [Article]
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. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Details1. Cytochrome P450 1A2

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

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. [Article]
Peg-interferon FDA label [File]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54

Peginterferon alfa-2a

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References

Enzymes

References