Peginterferon beta-1a

Identification

Name
Peginterferon beta-1a
Accession Number
DB09122
Description

Multiple Sclerosis (MS) is a chronic and inflammatory autoimmune disease of the central nervous system, disrupting communication between the brain and other parts of the body. Most patients diagnosed with this illness experience their initial disease symptoms between the age of 20 to 40, often the most productive years of life. Symptoms may include but are not limited to fatigue, gait changes, bowel or bladder dysfunction, abnormal muscle twitching, vision disturbance, and depressing or mood swings.11 MS is one of the most common causes of neurological disability in young adults and is found to occur more frequently in women than in men.3,12

Peginterferon beta-1a is an interferon therapy used for the management of relapsing forms of MS. It was originally approved by the FDA in 2014 for subcutaneous use, and was approved for intramuscular use in January 2021.13 Currently, it is the only approved pegylated interferon for the management of MS with an proven ability to reduce relapses and delay the progression of disability resulting from MS.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Interferons
Protein Chemical Formula
Not Available
Protein Average Weight
22500.0 Da (predicted)
Sequences
>Sequence
MSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCLKDRMNFDIPEEIKQLQQFQKEDAALTIY
EMLQNIFAIFRQDSSSTGWNETIVENLLANVYHQINHLKTVLEEKLEKEDFTRGKLMSSL
HLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINRLTGYLRN
Download FASTA Format
Synonyms
  • PEG IFN-beta-1a
  • Peginterferon beta-1a
  • Polyethylene glycol-interferon beta-1a
External IDs
  • BIIB-017
  • BIIB017

Pharmacology

Pharmacology
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Indication

Peginterferon beta-1a is indicated for the treatment of adult patients with relapsing forms of MS, including relapsing-remitting disease, clinically isolated syndrome, and active progressive secondary disease.13

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Peginterferon beta-1a likely reduces MS relapses and the progression of disability and brain lesions associated with MS by reducing inflammation.8,4 Specifically, IFN-beta decreases antigen presentation and T-cell proliferation. In addition, it modifies cytokine and matrix metalloproteinase (MMP) expression while restoring suppressor function.4

Mechanism of action

The mechanism by which peginterferon beta-1a exerts its effects in patients with multiple sclerosis is unknown13, however, it likely exerts its therapeutic actions by reducing inflammation. Through the binding of IFN-beta to its receptor9, a cascade of transcriptional events occur, decreasing the inflammation that normally results in the progression of MS. Immune cells are the most likely target of therapeutic effects exerted by IFN-beta.4

TargetActionsOrganism
UInterferon alpha/beta receptor 1
activator
downregulator
Humans
Absorption

Peginterferon beta-1a is almost completely absorbed after subcutaneous administration. After 125 microgram subcutaneous doses of peginterferon beta-1a to patient with MS, a Cmax of 280 pg/mL was reached between 1 and 1.5 days4, and the AUC over a 14 day dosing interval was 34.8 ng.hr/mL.13 The AUC ranges from 23.5-29.5 ng ml−1h, according to one pharmacokinetic study of patients with MS. Impairment of renal function may alter the Cmax and AUC of interferon beta-1a.4

Volume of distribution

The volume of distribution of peginterferon beta-1a is about 481 L.13 One pharmacokinetic study of patients administered interferon beta-1a revealed a volume of distribution in the range of 248-726 L, depending on the week of treatment.4

Protein binding

Protein binding information for peginterferon beta-1a is not readily available in the literature.

Metabolism

Peginterferon beta-1a is not extensively metabolized in the liver.13

Route of elimination

Peginterferon beta-1a is mainly cleared through the kidneys.4,13

Half-life

The mean half life of peginterferon beta-1a is approximately 78 h in patients with MS15, however, the half-life is highly variable and depends on duration of treatment and other factors.4

Clearance

The average steady state clearance of peginterferon beta-1a is about 4.1 L/h.13 One pharmacokinetic study revealed a clearance within the range of 3.68-7.89 L/h, depending on the week of treatment.4

Adverse Effects
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Toxicity

LD50 information for peginterferon beta-1a is not readily available in the literature. In clinical trials, no cases of overdoses occurred with the administration of interferon beta-1a at a dose of 75 μg administered subcutaneously 3 times a week.13 In a case report, a 38-year-old patient attempted suicide with about 6 or 7 pre-filled syringes containing 44 mug (12 MIU) of subcutaneous interferon beta-1a; symptoms were limited to malaise and skin erythema, which resolved within 24 hours with no intervention. Laboratory test results were unremarkable.10 In the case of an overdose with interferon-beta 1a, prescribing information suggests to contact the local poison control centre.15

Affected organisms
Not Available
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
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Peginterferon beta-1a.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Peginterferon beta-1a.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Peginterferon beta-1a.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Peginterferon beta-1a.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Peginterferon beta-1a.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Peginterferon beta-1a.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Peginterferon beta-1a.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Peginterferon beta-1a.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Peginterferon beta-1a.
AllopurinolThe risk or severity of adverse effects can be increased when Allopurinol is combined with Peginterferon beta-1a.
Interactions
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Food Interactions
No interactions found.

Products

Products
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International/Other Brands
Plegridy (Biogen)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PlegridyLiquid125 mcgSubcutaneousBiogen2015-09-29Not applicableCanada flag
PlegridyInjection, solution125 ug/0.5mLIntramuscularBiogen Inc.2021-01-29Not applicableUS flag
PlegridyInjection, solutionIntramuscularBiogen Netherlands B.V.2020-12-28Not applicableEU flag
PlegridyInjection, solutionSubcutaneousBiogen Netherlands B.V.2016-09-08Not applicableEU flag
PlegridyLiquid94 mcgSubcutaneousBiogenNot applicableNot applicableCanada flag
PlegridyInjection, solutionSubcutaneousBiogen Netherlands B.V.2016-09-08Not applicableEU flag
PlegridyLiquid63 mcgSubcutaneousBiogenNot applicableNot applicableCanada flag
PlegridyInjection, solutionSubcutaneousBiogen Netherlands B.V.2016-09-08Not applicableEU flag
PlegridyInjection, solutionIntramuscularBiogen Netherlands B.V.2020-12-28Not applicableEU flag
PlegridyInjection, solution125 ug/0.5mLSubcutaneousBiogen Inc.2014-08-15Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PlegridyPeginterferon beta-1a (63 mcg) + Peginterferon beta-1a (94 mcg)Kit; LiquidSubcutaneousBiogen2015-09-25Not applicableCanada flag
PlegridyPeginterferon beta-1a (63 mcg) + Peginterferon beta-1a (94 mcg)Kit; LiquidSubcutaneousBiogen2015-09-25Not applicableCanada flag
PlegridyPeginterferon beta-1a (94 ug/0.5mL) + Peginterferon beta-1a (63 ug/0.5mL)SubcutaneousBiogen Inc.2014-08-15Not applicableUS flag
PlegridyPeginterferon beta-1a (94 ug/0.5mL) + Peginterferon beta-1a (63 ug/0.5mL)SubcutaneousBiogen Inc.2014-08-15Not applicableUS flag
PLEGRİDY 63 MCG/0.5 ML+94 MCG/0.5 ML SC ENJEKSİYONLUK ÇÖZELTİ İÇEREN KULLANIMA HAZIR KALEM TEDAVİYE BAŞLAMA PAKETİ , 1 ADET 63 MGC/0.5 ML+1 ADET 94 MCG/0.5 MLPeginterferon beta-1a (63 mcg/0.5mL) + Peginterferon beta-1a (94 mcg/0.5mL)Injection; KitSubcutaneousGEN İLAÇ VE SAĞLIK ÜRÜNLERİ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
PLEGRİDY 63 MCG/0.5 ML+94 MCG/0.5 ML SC ENJEKSİYONLUK ÇÖZELTİ İÇEREN KULLANIMA HAZIR KALEM TEDAVİYE BAŞLAMA PAKETİ , 1 ADET 63 MGC/0.5 ML+1 ADET 94 MCG/0.5 MLPeginterferon beta-1a (63 mcg/0.5mL) + Peginterferon beta-1a (94 mcg/0.5mL)Injection; KitSubcutaneousGEN İLAÇ VE SAĞLIK ÜRÜNLERİ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
Plegridy PenPeginterferon beta-1a (94 ug/0.5mL) + Peginterferon beta-1a (63 ug/0.5mL)SubcutaneousBiogen Inc.2014-08-15Not applicableUS flag
Plegridy PenPeginterferon beta-1a (94 ug/0.5mL) + Peginterferon beta-1a (63 ug/0.5mL)SubcutaneousBiogen Inc.2014-08-15Not applicableUS flag

Categories

ATC Codes
L03AB13 — Peginterferon beta-1a
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
I8309403R0
CAS number
1211327-92-2

References

Synthesis Reference

Alessandra Del RioJoel Richard ; PEG-interferon-beta formulations. United States Patent US9138403B2. 2015-Sep-22

General References
  1. Newsome SD, Guo S, Altincatal A, Proskorovsky I, Kinter E, Phillips G, You X, Sabatella G: Impact of peginterferon beta-1a and disease factors on quality of life in multiple sclerosis. Mult Scler Relat Disord. 2015 Jul;4(4):350-7. doi: 10.1016/j.msard.2015.06.004. Epub 2015 Jun 14. [PubMed:26195056]
  2. Khan UT, Tanasescu R, Constantinescu CS: PEGylated IFNbeta-1a in the treatment of multiple sclerosis. Expert Opin Biol Ther. 2015 Jul;15(7):1077-84. doi: 10.1517/14712598.2015.1053206. Epub 2015 Jun 3. [PubMed:26036950]
  3. Ghasemi N, Razavi S, Nikzad E: Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. Epub 2016 Dec 21. [PubMed:28367411]
  4. Hu X, Cui Y, White J, Zhu Y, Deykin A, Nestorov I, Hung S: Pharmacokinetics and pharmacodynamics of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis in the randomized ADVANCE study. Br J Clin Pharmacol. 2015 Mar;79(3):514-22. doi: 10.1111/bcp.12521. [PubMed:25265472]
  5. Hoy SM: Peginterferon beta-1a: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs. 2015 Feb;29(2):171-9. doi: 10.1007/s40263-015-0227-1. [PubMed:25666445]
  6. Madsen C: The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis. Brain Behav. 2017 May 8;7(6):e00696. doi: 10.1002/brb3.696. eCollection 2017 Jun. [PubMed:28638705]
  7. Pestka S, Langer JA, Zoon KC, Samuel CE: Interferons and their actions. Annu Rev Biochem. 1987;56:727-77. doi: 10.1146/annurev.bi.56.070187.003455. [PubMed:2441659]
  8. Markowitz CE: Interferon-beta: mechanism of action and dosing issues. Neurology. 2007 Jun 12;68(24 Suppl 4):S8-11. doi: 10.1212/01.wnl.0000277703.74115.d2. [PubMed:17562848]
  9. Mastrangeli R, Iozzino L, Lanzoni L, Angiuoni G, Ferrao C, Izzo A, Fiumi S, Camerini F, Mascia M, Palinsky W, Bierau H: Biological Functions of Interferon beta-1a Are Enhanced By Deamidation. J Interferon Cytokine Res. 2016 Sep;36(9):534-41. doi: 10.1089/jir.2016.0025. Epub 2016 Jun 27. [PubMed:27348209]
  10. Falcone NP, Nappo A, Neuteboom B: Interferon beta-1a overdose in a multiple sclerosis patient. Ann Pharmacother. 2005 Nov;39(11):1950-2. doi: 10.1345/aph.1E416. Epub 2005 Oct 4. [PubMed:16204396]
  11. MS Society Document, Canada [Link]
  12. FDA approves new oral drug to treat multiple sclerosis [Link]
  13. FDA Approved Drug Products: PLEGRIDY (peginterferon beta-1a) injection, for subcutaneous or intramuscular use [Link]
  14. EMD Serono MSDS: Interferon beta 1a [Link]
  15. Product monograph: Avonex (interferon beta-1a) injection [Link]
  16. EMA Assessment Report: Plegridy (peginterferon beta-1a) for injection [Link]
KEGG Drug
D10483
PubChem Substance
347910413
RxNav
1546168
RxList
RxList Drug Page
Wikipedia
Peginterferon_beta-1a
AHFS Codes
  • 08:18.20 — Interferons
FDA label
Download (12.6 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)2
4RecruitingPreventionDisseminated Sclerosis1
4RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4WithdrawnSupportive CareRelapsing Remitting Multiple Sclerosis (RRMS)1
4WithdrawnTreatmentRelapsing Multiple Sclerosis (RMS)1
3CompletedTreatmentRelapsing Multiple Sclerosis (RMS)3
3RecruitingTreatmentCoronavirus (SARS-CoV) / Coronavirus Disease 2019 (COVID‑19) / INTERFERON1
3RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)2
3WithdrawnTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2Not Yet RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntramuscular
Injection, solutionIntramuscular
Injection, solutionIntramuscular125 ug/0.5mL
Injection, solutionParenteral; Subcutaneous
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous125 ug/0.5mL
Kit; liquidSubcutaneous
LiquidSubcutaneous125 mcg
LiquidSubcutaneous63 mcg
LiquidSubcutaneous94 mcg
InjectionSubcutaneous
Injection; kitSubcutaneous
SolutionSubcutaneous
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)100https://imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9BIOGN_AVONEX_KIT_30MCG_5ML_4BX.pdf
isoelectric point9.02https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch32_Lee_S_Human_Interferon-Beta_--Homo_sapiens-_-/Ch32_Lee_S_Human_Interferon-Beta_--Homo_sapiens_Human_Interferon_beta.html

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
Downregulator
Curator comments
Interferon 1 receptor is the target of beta interferon 1-a, however, the mechanism of action of this drug is not fully understood; some sources suggest down regulation of interferon 1 receptors, while others suggest activation of interferon 1 receptors.
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. Hu X, Cui Y, White J, Zhu Y, Deykin A, Nestorov I, Hung S: Pharmacokinetics and pharmacodynamics of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis in the randomized ADVANCE study. Br J Clin Pharmacol. 2015 Mar;79(3):514-22. doi: 10.1111/bcp.12521. [PubMed:25265472]
  2. Pestka S, Langer JA, Zoon KC, Samuel CE: Interferons and their actions. Annu Rev Biochem. 1987;56:727-77. doi: 10.1146/annurev.bi.56.070187.003455. [PubMed:2441659]
  3. Mastrangeli R, Iozzino L, Lanzoni L, Angiuoni G, Ferrao C, Izzo A, Fiumi S, Camerini F, Mascia M, Palinsky W, Bierau H: Biological Functions of Interferon beta-1a Are Enhanced By Deamidation. J Interferon Cytokine Res. 2016 Sep;36(9):534-41. doi: 10.1089/jir.2016.0025. Epub 2016 Jun 27. [PubMed:27348209]
  4. Hu X, Seddighzadeh A, Stecher S, Zhu Y, Goyal J, Matson M, Marbury T, Smith W, Nestorov I, Hung S: Pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-1a in subjects with normal or impaired renal function. J Clin Pharmacol. 2015 Feb;55(2):179-88. doi: 10.1002/jcph.390. Epub 2014 Sep 23. [PubMed:25187030]
  5. Liberati AM, Fizzotti M, Proietti MG, Di Marzio R, Schippa M, Biscottini B, Senatore M, Berruto P, Canali S, Peretti G, et al.: Biochemical host response to interferon-beta. J Interferon Res. 1988 Dec;8(6):765-77. doi: 10.1089/jir.1988.8.765. [PubMed:3068316]
  6. EMA Assessment Report: Plegridy (peginterferon beta-1a) for injection [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
Curator comments
A study in rats demonstrated that interferon beta-1a down regulated CYP1A2 in rats. Clinical relevance is unknown.
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. Delaporte E, Renton KW: Cytochrome P4501A1 and cytochrome P4501A2 are downregulated at both transcriptional and post-transcriptional levels by conditions resulting in interferon-alpha/beta induction. Life Sci. 1997;60(10):787-96. doi: 10.1016/s0024-3205(97)00006-4. [PubMed:9064483]

Drug created on September 23, 2015 15:59 / Updated on April 20, 2021 12:57