Peginterferon alpha-2b

Compound Name:Peginterferon alpha-2bMolecular Target:Type I interferon receptorsMolecular Structure:Recombinant human physiologic protein covalently conjugated to polyethylene glycolLicensed Indication:Chronic hepatitis CManufacturer and/or Distributor:Schering (Merck)Initial FDA Approval2001SummaryPeginterferon alpha-2b (Pegintron) is a recombinant human Type I interferon produced in E. coli and covalently conjugated to monomethoxy polyethylene glycol (PEG) (total MW 31 kDa). The interferon moiety has the usual physiologic effects of Type I interferons, including inhibition of viral replication, cellular proliferation, and angiogenesis; as well as pro-apoptotic and immunomodulatory activities. It binds to the Type I interferon receptor, which is widely present on many cell types. This binding initiates a signaling cascade that leads to the diverse physiological effects of Type I interferons. The addition of the PEG moiety results in a five-fold increase in the in vivo half-life of the agent. Peginterferon alpha-2b is administered by weekly subcutaneous injections.

 Peginterferon alpha-2b was approved by the FDA in 2001 for the treatment of chronic hepatitis C in patients, both adult and children (over 3 years of age) without excessive liver dysfunction. It is normally used in combination with ribavirin (a nucleotide analog) and a protease inhibitor or with ribavirin alone. It is indicated for use as monotherapy in previously untreated adult patients who cannot take ribavirin. Particularly as combination therapy, it can induce a sustained virologic response (absence of detectable virus in the blood 6 months after cessation of treatment) in about 50% of patients.

 Like other Type I interferons, peginterferon alpha-2b induces local injection site reactions and systemic flu-like symptoms. Serious safety concerns include hypersensitivity and a wide variety of manifestations affecting multiple systems: cardiopulmonary, GI, endocrine, renal system, hematopoietic, ophthalmologic, cerebrovascular, and infectious, as well as the potential to induce autoimmune syndromes and growth retardation in children. It is contraindicated in patients with hepatitic decompensation, autoimmune hepatitis, or known hypersensitivity to the product. Additional safety concerns would be related to co-administered ribavirin. Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. Additional safety concerns would be related to co-administered ribavirin.References

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1. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-965.

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