Identification

Name
Human interferon beta
Accession Number
DB14999
Description

Human interferon beta is a polypeptide used in the management of relapsing forms of Multiple Sclerosis (MS), and was initially approved by the FDA in 1992.9 Multiple Sclerosis is a devastating neurodegenerative disease that is usually progressive and significantly debilitating with a profound impact on the quality of life.3

Interferon beta is currently being studied as a possible treatment for COVID-19, which results from infection with the novel 2019 SARS-CoV-2 virus.8 Interferon-beta has been used in the past in clinical studies with other coronaviruses due to its demonstrated activity against the virus causing Middle Eastern Respiratory Syndrome (MERS). It is therefore a potential drug candidate for SARS-CoV-2 based on viral genetic similarity.2,10

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
Protein Chemical Formula
Not Available
Protein Average Weight
40036.0 Da
Sequences
Not Available
Synonyms
  • Fibroblast interferon
  • FIF
  • Interferon beta
  • Interferon beta (human)
  • Interferon-beta
External IDs
  • SNG 001
  • SNG-001
  • SNG001

Pharmacology

Indication

This drug is indicated to treat relapsing forms of Multiple Sclerosis (MS) in adults, which includes clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease.9

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Interferon-beta has antiviral and immunomodulatory effects. It reduces demyelination, the main component of Multiple Sclerosis pathophysiology, reducing the clinical frequency of MS attacks and slowing disease progression.1,3,12

In vitro studies have shown that beta interferon reduces the replication of certain coronaviruses in lung tissue.7 Retrospective studies using combinations of mycophenolate mofetil and beta interferon showed improved survival against MERS-CoV, the virus that causes Middle Eastern Respiratory Syndrome (MERS). 6

Mechanism of action

Part of the pathophysiology of MS is immune cell activation in addition to degradation of the blood–brain barrier (BBB), resulting in both neural demyelination and axon injury. Immunomodulating drugs such as interferon-beta decrease the inflammation that results in demyelination of nerves. Binding of interferon-beta to type 1 interferon receptors induces a series of beneficial transcriptional JAK/STAT pathway changes. This decreases antigen presentation as well as the proliferation of inflammatory T-cells, reducing the inflammation associated with MS. It also changes the expression of cytokine and matrix metalloproteinase (MMP).1,4

TargetActionsOrganism
AInterferon alpha/beta receptor 1
binder
Humans
Absorption

Beta interferon has a bioavailability of about 30% after subcutaneous or intramuscular administration, demonstrating peak serum concentrations within several hours of a dose. Peak interferon beta-1b concentrations are achieved between 1-8 hours post-dose, measuring about 40 IU/mL.9 After injection, it is absorbed mainly by the lymphatic route.5 Prescribing information for interferon beta-1b indicates a bioavailability of 50%.12 Concentrations of beta interferon are detectable in the circulation 1-2 to days after administration.5

Volume of distribution

The average state volume of distribution for beta interferon is 0.25 L/kg to 2.88 L/kg.12 Another reference mentions a volume of distribution of 120 L.5 Beta interferon is distributed throughout the body after extravasation across the vascular wall into the tissue after injection. It likely does not cross the blood-brain barrier, and it is unclear whether beta interferon crosses the placenta.5

Protein binding
Not Available
Metabolism

Data regarding the metabolism of beta interferon is not readily available in the literature.

Route of elimination

Beta interferon is excreted by hepatic and renal pathways, with renal pathways accountable for about 40% of its clearance.5

Half-life

The mean terminal elimination half-life of interferon-beta varies from 8 minutes to about 4 hours.5,9

Clearance

Average serum clearance in a pharmacokinetic study of beta-interferon 1b ranged from 9.4 mL/min•kg-1 to 28.9 mL/min•kg-1.12 Another study revealed a clearance ranging between 0.3 to 1.4 L/h/kg.5

Adverse Effects
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Toxicity

LD50 information for beta interferon is not readily available in the literature.

Overdose information

Following an overdose with a very high dose of beta interferon, one patient described in a case report experienced a modest rise in body temperature with diffuse limb and truncal erythema. The symptoms resolved within 24 hours. Biochemical and hematologic parameters were nonremarkable after the overdose.6 In the case of an overdose, discontinue beta interferon and resume when the patient has returned to baseline function.

Affected organisms
  • SARS-CoV-2
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
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Human interferon beta.
BromotheophyllineThe metabolism of Bromotheophylline can be decreased when combined with Human interferon beta.
CaffeineThe metabolism of Caffeine can be decreased when combined with Human interferon beta.
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Human interferon beta.
MercaptopurineThe metabolism of Mercaptopurine can be decreased when combined with Human interferon beta.
OxtriphyllineThe metabolism of Oxtriphylline can be decreased when combined with Human interferon beta.
PentoxifyllineThe metabolism of Pentoxifylline can be decreased when combined with Human interferon beta.
TheophyllineThe metabolism of Theophylline can be decreased when combined with Human interferon beta.
ZidovudineThe risk or severity of adverse effects can be increased when Human interferon beta is combined with Zidovudine.
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
No interactions found.

Products

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
V9GU1EM8SF
CAS number
74899-71-1

References

General References
  1. 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]
  2. Al Ghamdi M, Alghamdi KM, Ghandoora Y, Alzahrani A, Salah F, Alsulami A, Bawayan MF, Vaidya D, Perl TM, Sood G: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis. 2016 Apr 21;16:174. doi: 10.1186/s12879-016-1492-4. [PubMed:27097824]
  3. Huang WJ, Chen WW, Zhang X: Multiple sclerosis: Pathology, diagnosis and treatments. Exp Ther Med. 2017 Jun;13(6):3163-3166. doi: 10.3892/etm.2017.4410. Epub 2017 Apr 28. [PubMed:28588671]
  4. Kasper LH, Reder AT: Immunomodulatory activity of interferon-beta. Ann Clin Transl Neurol. 2014 Aug;1(8):622-31. doi: 10.1002/acn3.84. Epub 2014 Jul 23. [PubMed:25356432]
  5. Hegen H, Auer M, Deisenhammer F: Pharmacokinetic considerations in the treatment of multiple sclerosis with interferon-beta. Expert Opin Drug Metab Toxicol. 2015;11(12):1803-19. doi: 10.1517/17425255.2015.1094055. Epub 2015 Sep 30. [PubMed:26419922]
  6. 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]
  7. Chan RW, Chan MC, Agnihothram S, Chan LL, Kuok DI, Fong JH, Guan Y, Poon LL, Baric RS, Nicholls JM, Peiris JS: Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J Virol. 2013 Jun;87(12):6604-14. doi: 10.1128/JVI.00009-13. Epub 2013 Apr 3. [PubMed:23552422]
  8. World Health Organization: Landscape analysis of therapeutics as of February 17 2020 [Link]
  9. FDA approved products: Extravia (interferon beta-1b) subcutaneous injection [Link]
  10. Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
  11. Product monograph: Avonex pen (interferon beta 1a) [Link]
  12. FDA approved products: Betaseron (interferon beta 1b) subcutaneous injection [Link]
  13. EMD Serono MSDS: Interferon beta 1a [Link]
  14. ThPDB: Interferon beta1a [Link]
  15. DailyMed: Avonex (interferon beta1a) solution for injection [Link]
RxNav
4381
MSDS
Download (43.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDisseminated Sclerosis1
4CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4WithdrawnTreatmentRelapsing Multiple Sclerosis (RMS)1
3CompletedTreatmentDisseminated Sclerosis1
3CompletedTreatmentDisseminated Sclerosis / Macular Edema / Uveitis, Intermediate1
3CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3RecruitingTreatmentInfections, Coronavirus / Novel Coronavirus Infectious Disease (COVID-19) / Severe Acute Respiratory Syndrome1
3RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3TerminatedTreatmentRelapsing Multiple Sclerosis (RMS)1
3Unknown StatusTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
hydrophobicity-0.427http://crdd.osdd.net/raghava/thpdb/display_thppid_sub.php?details=Th1049
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

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
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. 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]
  2. Kasper LH, Reder AT: Immunomodulatory activity of interferon-beta. Ann Clin Transl Neurol. 2014 Aug;1(8):622-31. doi: 10.1002/acn3.84. Epub 2014 Jul 23. [PubMed:25356432]
  3. Haji Abdolvahab M, Mofrad MR, Schellekens H: Interferon Beta: From Molecular Level to Therapeutic Effects. Int Rev Cell Mol Biol. 2016;326:343-72. doi: 10.1016/bs.ircmb.2016.06.001. Epub 2016 Jul 20. [PubMed:27572132]
  4. Kole A, He J, Rivollier A, Silveira DD, Kitamura K, Maloy KJ, Kelsall BL: Type I IFNs regulate effector and regulatory T cell accumulation and anti-inflammatory cytokine production during T cell-mediated colitis. J Immunol. 2013 Sep 1;191(5):2771-9. doi: 10.4049/jimmunol.1301093. Epub 2013 Aug 2. [PubMed:23913971]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
Curator comments
Data regarding this enzyme action of interferon beta are scarce in the literature. This is unlikely to result in any CYP1A2 mediated drug interactions.
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]
  2. Christensen H, Hermann M: Immunological response as a source to variability in drug metabolism and transport. Front Pharmacol. 2012 Feb 10;3:8. doi: 10.3389/fphar.2012.00008. eCollection 2012. [PubMed:22363283]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA approved products: Extravia (interferon beta-1b) subcutaneous injection [Link]

Drug created on May 20, 2019 08:40 / Updated on July 28, 2020 21:41

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