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Peginterferon alfa-2b

peg interferon alfa 2b, peg interferon alfa-2b price in india
Pegylated interferon alfa-2b, sold under the brand name is PegIntron among others, is a medication used to treat hepatitis C and melanoma For hepatitis C it is typically used with ribavirin and cure rates are between 33 and 82% For melanoma it is used in addition to surgery It is given by injection under the skin

Side effects are common They may include headache, feeling tired, mood changes, trouble sleeping, hair loss, nausea, pain at the site of injection, and fever Severe side effects may include psychosis, liver problems, blood clots, infections, or an irregular heartbeat Use with ribavirin is not recommended during pregnancy Pegylated interferon alfa-2b is in the alpha interferon family of medications It is pegylated to protects the molecule from breakdown

Pegylated interferon alfa-2b was approved for medical use in the United States in 2001 It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system The wholesale cost in the developing world is between 500 and 4,800 USD for 12 weeks In the United States this costs about 8,40000 USD, while in the United Kingdom 12 weeks costs the NHS about 159500 pounds

Contents

  • 1 Medical uses
    • 11 Host genetic factors
  • 2 Side effects
  • 3 Mechanism of action
  • 4 History
  • 5 References
  • 6 External links

Medical uses

It is used to treat hepatitis C and melanoma For hepatitis C it is typically used with ribavirin For melanoma it is used in addition to surgery

For hepatitis C it may also be used with boceprevir, telaprevir, simeprevir, or sofosbuvir

Host genetic factors

For genotype 1 hepatitis C treated with pegylated interferon-alfa-2a or pegylated interferon-alfa-2b combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment This finding, originally reported in Nature, showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more likely to achieve sustained virological response after the treatment than others A later report from Nature demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus

Side effects

Common side effects include headache, feeling tired, mood changes, trouble sleeping, hair loss, nausea, pain at the site of injection, and fever Severe side effects may include psychosis, liver problems, blood clots, infections, or an irregular heartbeat Use with ribavirin is not recommended during pregnancy

Mechanism of action

One of the major mechanisms of PEG-interferon alpha-2b utilizes the JAK-STAT signaling pathway The basic mechanism works such that PEG-interferon alpha-2b will bind to its receptor, interferon-alpha receptor 1 and 2 IFNAR1/2 Upon ligand binding the Tyk2 protein associated with IFNAR1 is phosphorylated which in turn phosphorylates Jak1 associated with IFNAR2 This kinase continues its signal transduction by phosphorylation of signal transducer and activator of transcription STAT 1 and 2 via Jak 1 and Tyk2 respectively The phosphorylated STATs then dissociate from the receptor heterodimer and form an interferon transcription factor with p48 and IRF9 to form the interferon stimulate transcription factor-3 ISGF3 This transcription factor then translocates to the nucleus where it will transcribe several genes involved in cell cycle control, cell differentiation, apoptosis, and immune response

PEG-interferon alpha-2b acts as a multifunctional immunoregulatory cytokine by transcribing several genes, including interleukin 4 IL4 This cytokine is responsible for inducing T helper cells to become type 2 helper T cells This ultimately results in the stimulation of B cells to proliferate and increase their antibody production This ultimately allows for an immune response, as the B cells will help to signal the immune system that a foreign antigen is present

Another major mechanism of type I interferon alpha IFNα is to stimulate apoptosis in malignant cell lines Previous studies have shown that IFNα can cause cell cycle arrest in U266, Daudi, and Rhek-1 cell lines

A follow-up study researched to determine if the caspases were involved in the apoptosis seen in the previous study as well as to determine the role of mitochondrial cytochrome c release The study confirmed that there was cleavage of caspase-3, -8, and -9 All three of these cysteine proteases play an important role in the initiation and activation of the apoptotic cascade Furthermore, it was shown that IFNα induced a loss in the mitochondrial membrane potential which resulted in the release of cytochrome c from the mitochondria Follow-up research is currently being conducted to determine the upstream activators of the apoptotic pathway that are induced by IFNα

History

It was developed by Schering-Plough Merck studied it for melanoma under the brand name Sylatron It was approved for this use in April 2011

References

  1. ^ a b c d e f g h i j k l "Peginterferon Alfa-2b Professional Patient Advice - Drugscom" wwwdrugscom Archived from the original on 16 January 2017 Retrieved 12 January 2017 
  2. ^ "ViraferonPeg Pen 50, 80, 100, 120 or 150 micrograms powder and solvent for solution for injection in pre-filled pen CLEAR CLICK - Summary of Product Characteristics SPC - eMC" wwwmedicinesorguk Archived from the original on 13 January 2017 Retrieved 12 January 2017 
  3. ^ a b c d "Peginterferon alfa-2b PegIntron - Treatment - Hepatitis C Online" wwwhepatitiscuwedu Archived from the original on 23 December 2016 Retrieved 12 January 2017 
  4. ^ "WHO Model List of Essential Medicines 19th List" PDF World Health Organization April 2015 Archived PDF from the original on 13 December 2016 Retrieved 8 December 2016 
  5. ^ "Inclusion of the injectable formulation of peginterferon alfa-2a and -2b is proposed for the treatment of hepatitis C among adults" PDF whoint p 11 Archived PDF from the original on 13 January 2017 Retrieved 12 January 2017 
  6. ^ British national formulary : BNF 69 69 ed British Medical Association 2015 p 639 ISBN 9780857111562 
  7. ^ Ge D, Fellay J, Thompson AJ, et al 2009 "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance" Nature 461 7262: 399–401 doi:101038/nature08309 PMID 19684573 
  8. ^ Thomas DL, Thio CL, Martin MP, et al 2009 "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus" Nature 461 7265: 798–801 doi:101038/nature08463 PMC 3172006  PMID 19759533 
  9. ^ Ward AC, Touw I, Yoshimura A January 2000 "The Jak-Stat pathway in normal and perturbed hematopoiesis" Blood 95 1: 19–29 PMID 10607680 
  10. ^ PATHWAYS :: IFN alpha
  11. ^ Thomas H, Foster G, Platis D February 2004 "Corrigendum to Mechanisms of action of interferon and nucleoside analogues J Hepatol 39 2003 S93–8" J Hepatol 40 2: 364 doi:101016/jjhep200312003 
  12. ^ Sangfelt O, Erickson S, Castro J, Heiden T, Einhorn S, Grandér D March 1997 "Induction of apoptosis and inhibition of cell growth are independent responses to interferon-alpha in hematopoietic cell lines" Cell Growth Differ 8 3: 343–52 PMID 9056677 Archived from the original on 2014-04-26 
  13. ^ Thyrell L, Erickson S, Zhivotovsky B, et al February 2002 "Mechanisms of Interferon-alpha induced apoptosis in malignant cells" Oncogene 21 8: 1251–62 doi:101038/sjonc1205179 PMID 11850845 

External links

  • "Peginterferon alfa-2b Approval Information" Drugs: Development & Approval Process US Food and Drug Administration 2009 
  • "Peg Intron Website"
  • "Medicines patent loophole 'found'" BBC News 2 January 2007 
  • "PEG-Intron Peginterferon Alfa-2B — Platelet Count Decreased — Suspected Cause — Side Effect Reports" DrugLibcom 
  • Pharmacy and pharmacology portal
  • Medicine portal

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