Chemistry:Peginterferon alfa-2b

From HandWiki
Short description: Pharmaceutical drug
Peginterferon alfa-2b
Clinical data
Trade namesPegIntron, Sylatron, ViraferonPeg, others
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa605030
License data
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life22–60 hrs
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC860H1353N229O255S9
Molar mass19269.17 g·mol−1
 ☒N☑Y (what is this?)  (verify)

Pegylated interferon alfa-2b is a drug used to treat melanoma, as an adjuvant therapy to surgery.[3] Also used to treat hepatitis C (typically, in combination with ribavarin), it is no longer recommended due to poor efficacy and adverse side-effects.[4] Subcutaneous injection is the preferred delivery method.[3]

Belonging to the alpha interferon family of medications, the molecule is PEGylated to prevent breakdown.[3][4] Approval for medical use in the United States was granted in 2001.[3] It is on the World Health Organization's List of Essential Medicines as a therapy for chronic hepatitis C.[5][6]

Medical uses

Hepatitis

Till around 2010, PEGylated interferon alfa-2b in combination with ribavirin, was part of the standard regimen used in management of hepatitis C.[4][7] Ribivarin helped in increasing the Sustained Virologic Response (SVR) even more.[8] Developed by Schering-Plough, the drug was approved by Food and Drug Administration (FDA) of the United States in 2001, and has been on the World Health Organization's List of Essential Medicines as a therapy for chronic hepatitis C since 2013.[4][5][6]

A 2013 meta-analysis over Clinical Infectious Diseases noted the combination-treatment to be safe as well as effective for children and adolescents; other meta-analyses had noted the same for adult population.[9] A 2012 meta-analysis had found PEGylated interferon alfa-2a to be the more effective variant for treatment-naive patients.[10]

With the advent of Direct-Acting-Antivirals (DAAs — ), interferon-based treatment regimens gradually fell out of fashion due to relatively poor efficacy and high frequency of adverse side-effects.[4][7][11] No longer recommended, the use of PEGylated interferon alfa-2b has essentially ceased in all countries, where DAA therapeutics are available.[12][4]

Melanoma

For high-risk melanoma, it is used as an adjuvant therapy to surgery in some countries.[3][13] It was first approved for the purpose by FDA on March 29, 2011, based on a single phase III trial.[14][15]

The usage remains controversial — frequency of severe side-effects is high, overall survival benefits substantially vary across different trials, and there is no consensus on the dosage regimen.[16] Meta-analyses have suggested that the drug might be more helpful for patients with ulcerated primary lesion.[16]

COVID-19

On 23 April 2021, the Drugs Controller General of India approved emergency use of the medication (upon a request by Cadila Healthcare; trade name is Virafin) for treating moderate COVID-19 infections.[17] No publication (or preprint) yet exists; the phase II trial was poorly designed and not robust.[17]

Side effects

Adverse side effects are common and often require dose reduction or outright discontinuation.[4][8]

Common side effects include fatigue, headache, insomnia, depression, mood swings, hair loss, nausea, diarrhea, myalgia and associated skeletal pain, anorexia, fever etc.[3][4] Relatively rare effects include imbalance of thyroid hormones, xerostomia, thrombocytopenia, hepatomegaly, pharyngitis, cough, psychosis, rashes, arrythmia, anemia etc.[3] Severe side effects may include a range of potentially fatal neuropsychiatric, autoimmune, ischemic, or infectious disorders.[3][4]

Mechanism of action

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,[18] 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[19] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

References

  1. ↑ "PegIntron- peginterferon alfa-2b injection, powder, lyophilized, for solution PegIntron- peginterferon alfa-2b kit". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b70816bb-913a-467f-acb8-67ef62cf8dac. 
  2. ↑ "Sylatron- peginterferon alfa-2b kit". 28 August 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3874c95c-092e-4cd5-b104-6ed2bc391b0e. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Peginterferon Alfa-2b (Professional Patient Advice) - Drugs.com". https://www.drugs.com/ppa/peginterferon-alfa-2b.html. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 "Peginterferon alfa-2b (PegIntron)". Infectious Diseases Education & Assessment, University of Washington. January 2021. http://www.hepatitisc.uw.edu/page/treatment/drugs/peginterferon-alfa-2b-drug. 
  5. ↑ 5.0 5.1 World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  6. ↑ 6.0 6.1 "eEML - Electronic Essential Medicines List". https://list.essentialmeds.org/medicines/522. 
  7. ↑ 7.0 7.1 "Systematic Review: Impact of Interferon-based Therapy on HCV-related Hepatocellular Carcinoma". Scientific Reports 5 (1): 9954. May 2015. doi:10.1038/srep09954. PMID 25963067. 
  8. ↑ 8.0 8.1 The Selection and Use of Essential Medicines: Report of the WHO Expert Committee. WHO Technical Report Series: 985. Geneva: World Health Organization. 2013. pp. 42. https://list.essentialmeds.org/files/trs/PXjEBzgbrMCpEHRGYEuB56NGdqGSBShvFrSzvRTL.pdf. 
  9. ↑ "Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis". Clinical Infectious Diseases 56 (7): 961–7. April 2013. doi:10.1093/cid/cis1031. PMID 23243171. 
  10. ↑ "Peginterferon alfa-2a is superior to peginterferon alfa-2b in the treatment of naïve patients with hepatitis C virus infection: meta-analysis of randomized controlled trials". Digestive Diseases and Sciences 56 (8): 2221–6. August 2011. doi:10.1007/s10620-011-1765-0. PMID 21643737. 
  11. ↑ "Direct-acting antivirals for the treatment of hepatitis C virus infection". https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection. 
  12. ↑ "Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection". Pharmacology & Therapeutics 183: 118–126. March 2018. doi:10.1016/j.pharmthera.2017.10.009. PMID 29024739. 
  13. ↑ "Update on PEG-interferon α-2b as adjuvant therapy in melanoma". Anticancer Research 32 (9): 3901–9. September 2012. PMID 22993335. https://ar.iiarjournals.org/content/32/9/3901. 
  14. ↑ "U.S. Food and Drug Administration Approval: peginterferon-alfa-2b for the adjuvant treatment of patients with melanoma" (in zh). The Oncologist 17 (10): 1323–8. 2012. doi:10.1634/theoncologist.2012-0123. PMID 23002124. 
  15. ↑ "Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial" (in English). Lancet 372 (9633): 117–26. July 2008. doi:10.1016/S0140-6736(08)61033-8. PMID 18620949. https://www.zora.uzh.ch/id/eprint/13909/1/EORTC18991_Lancet_FINAL_FINAL_Eggermont_et_al_2008_2_12.pdf. 
  16. ↑ 16.0 16.1 "The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma". Expert Opinion on Drug Safety 16 (8): 933–940. August 2017. doi:10.1080/14740338.2017.1343301. PMID 28627943. 
  17. ↑ 17.0 17.1 "DCGI Approves Virafin for Moderate COVID. Where's the Evidence It Works?" (in en-GB). 2021-04-24. https://science.thewire.in/the-sciences/zydus-virafin-pegylated-interferon-alpha-2b-india-dcgi-approve-covid-trial-methods-flaw/. 
  18. ↑ "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature 461 (7262): 399–401. September 2009. doi:10.1038/nature08309. PMID 19684573. Bibcode: 2009Natur.461..399G. 
  19. ↑ "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature 461 (7265): 798–801. October 2009. doi:10.1038/nature08463. PMID 19759533. Bibcode: 2009Natur.461..798T. 

External links




Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Peginterferon_alfa-2b&oldid=3333112"