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Peginterferon alfa-2b

Clinical data
Trade names	PegIntron, Sylatron, ViraferonPeg, others
AHFS/Drugs.com	Professional Drug Facts
MedlinePlus	a605030
Routes of administration	Subcutaneous injection
ATC code	L03AB10 (WHO) L03AB60 (WHO)
Legal status
Legal status	US: ℞-only EU: Rx-only
Pharmacokinetic data
Elimination half-life	22–60 hrs
Identifiers
IUPAC name PEGylated human interferon alpha 2b
CAS Number	215647-85-1
IUPHAR/BPS	7462
DrugBank	DB00022
ChemSpider	none
UNII	G8RGG88B68
KEGG	D02745
ChEMBL	ChEMBL1201561
ECHA InfoCard	100.208.164
Chemical and physical data
Formula	C860H1353N229O255S9
Molar mass	19269.17 g·mol
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Pegylated interferon alfa-2b is a drug used to treat melanoma, as an adjuvant therapy to surgery. Also used to treat hepatitis C (typically, in combination with ribavarin), it is no longer recommended due to poor efficacy and adverse side-effects. Subcutaneous injection is the preferred delivery method.

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

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. Ribivarin helped in increasing the Sustained Virologic Response (SVR) even more. 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.

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. A 2012 meta-analysis had found PEGylated interferon alfa-2a to be the more effective variant for treatment-naive patients.

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. No longer recommended, the use of PEGylated interferon alfa-2b has essentially ceased in all countries, where DAA therapeutics are available.

Melanoma

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

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. Meta-analyses have suggested that the drug might be more helpful for patients with ulcerated primary lesion.

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. No publication (or preprint) yet exists; the phase II trial was poorly designed and not robust.

Side effects

Adverse side effects are common and often require dose reduction or outright discontinuation.

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

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, 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.

References

1. "PegIntron- peginterferon alfa-2b injection, powder, lyophilized, for solution PegIntron- peginterferon alfa-2b kit". DailyMed. Retrieved 28 September 2020.
2. "Sylatron- peginterferon alfa-2b kit". DailyMed. 28 August 2019. Retrieved 28 September 2020.
3. ^ "Peginterferon Alfa-2b (Professional Patient Advice) - Drugs.com". www.drugs.com. Archived from the original on 16 January 2017. Retrieved 12 January 2017.
4. ^ "Peginterferon alfa-2b (PegIntron)". Hepatitis C Online. Infectious Diseases Education & Assessment, University of Washington. January 2021. Retrieved 12 January 2017.
5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
6. ^ "eEML - Electronic Essential Medicines List". list.essentialmeds.org. Retrieved 21 May 2021.
7. ^ Hsu CS, Chao YC, Lin HH, Chen DS, Kao JH (May 2015). "Systematic Review: Impact of Interferon-based Therapy on HCV-related Hepatocellular Carcinoma". Scientific Reports. 5 (1): 9954. doi:10.1038/srep09954. PMC 4428066. PMID 25963067.
8. ^ The Selection and Use of Essential Medicines: Report of the WHO Expert Committee (PDF). WHO Technical Report Series: 985. Geneva: World Health Organization. 2013. p. 42.
9. Druyts E, Thorlund K, Wu P, Kanters S, Yaya S, Cooper CL, Mills EJ (April 2013). "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. doi:10.1093/cid/cis1031. PMID 23243171.
10. Singal AK, Jampana SC, Anand BS (August 2011). "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. doi:10.1007/s10620-011-1765-0. PMID 21643737. S2CID 34328390.
11. Pockros PJ. "Direct-acting antivirals for the treatment of hepatitis C virus infection". UpToDate. Retrieved 21 May 2021.
12. Spengler U (March 2018). "Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection". Pharmacology & Therapeutics. 183: 118–126. doi:10.1016/j.pharmthera.2017.10.009. PMID 29024739. S2CID 3337006.
13. Di Trolio R, Simeone E, Di Lorenzo G, Grimaldi AM, Romano A, Ayala F, et al. (September 2012). "Update on PEG-interferon α-2b as adjuvant therapy in melanoma". Anticancer Research. 32 (9): 3901–9. PMID 22993335.
14. Herndon TM, Demko SG, Jiang X, He K, Gootenberg JE, Cohen MH, et al. (2012). "U.S. Food and Drug Administration Approval: peginterferon-alfa-2b for the adjuvant treatment of patients with melanoma". The Oncologist (in Chinese). 17 (10): 1323–8. doi:10.1634/theoncologist.2012-0123. PMC 3481898. PMID 23002124.
15. Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. (July 2008). "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" (PDF). Lancet. 372 (9633): 117–26. doi:10.1016/S0140-6736(08)61033-8. PMID 18620949. S2CID 665063.
16. ^ Trinh VA, Zobniw C, Hwu WJ (August 2017). "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. doi:10.1080/14740338.2017.1343301. PMID 28627943. S2CID 22139797.
17. ^ Borana R (24 April 2021). "DCGI Approves Virafin for Moderate COVID. Where's the Evidence It Works?". The Wire Science. Retrieved 20 May 2021.
18. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. (September 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. Bibcode:2009Natur.461..399G. doi:10.1038/nature08309. PMID 19684573. S2CID 1707096.
19. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, et al. (October 2009). "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature. 461 (7265): 798–801. Bibcode:2009Natur.461..798T. doi:10.1038/nature08463. PMC 3172006. PMID 19759533.

External links

• Medicines patent loophole 'found' at the BBC, 2007
• PEG-Intron (Peginterferon Alfa-2B) — Platelet Count Decreased from DrugLib.com

• Medicine
• Viruses

• Immunostimulants
• Drugs developed by Schering-Plough
• Drugs developed by Merck & Co.
• World Health Organization essential medicines