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| Primary information |
|---|
| ID | 10136 |
| Therapeutic ID | Th1019 |
| Protein Name | Peginterferon alfa-2b |
| Sequence | >Th1019_Peginterferon_alfa-2b
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
|
| Molecular Weight | 31000 |
| Chemical Formula | C130H219N43O42 |
| Isoelectric Point | 5.99 |
| Hydrophobicity | NA |
| Melting point | 61 |
| Half-life | Approximately 40 hours (range 22 to 60 hours) in patients with HCV infection |
| Description | Peginterferon alfa-2b is a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol (PEG). The average molecular weight of the PEG portion of the molecule is 12,000 daltons. The average molecular weight of the PEG-Intron molecule is approximately 31,000 daltons. The specific activity of peginterferon alfa-2b is approximately 0.7 x 108 IU/mg protein. Interferon alfa-2b is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon gene from human leukocytes. The PEG strand protects the molecule in vivo from proteolytic breakdown, substantially increases its in vivo half-life, and reduces immunogenicity by wrapping around and physically hindering access to the protein portion of the molecule. |
| Indication/Disease | Used for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha who have compensated liver disease and are at least 18 years of age. |
| Pharmacodynamics | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. |
| Mechanism of Action | It binds to type I interferon receptors IFNAR1 and IFNAR2c which upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | After a single subcutaneous dose of peginterferon alfa-2b, the mean absorption half-life was 4.6 hours. |
| NA |
| Clearance | Oral cl=22 mL/hr/kg [patients with HCV infection], Renal elimination accounts for 30% of the clearance. |
| Categories | Adjuvants, Immunologic, Alcohols, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cancer immunotherapy, Compounds used in a research, industrial, or household setting, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 CYP2C9 Inducers, Cytochrome P-450 CYP2C9 Inducers (weak), Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors (weak), Cytochrome P-450 Enzyme Inducers, Cytochrome P-450 Enzyme Inhibitors, Cytokines, Drug Carriers, Ethylene Glycols, Glycols, Hepatitis C, Immunosuppressive Agents, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferon-alpha, Interferons, Macromolecular Substances, Myelosuppressive Agents, Pegylated agents, Peptides, Polymers, Proteins, Treatments for Hepatitis C |
| Patents Number | CA2329474 |
| Date of Issue | 26-Feb-2002 |
| Date of Expiry | 31-Oct-2016 |
| Drug Interaction | Dyphylline.Interferon increases the effect and toxicity of theophylline |
| Target | NA |
| Brand Name | Sylatron |
| Company | Merck Sharp & Dohme Corp. |
| Brand Description | Merck Sharp & Dohme Corp. |
| Prescribed For | SYLATRON™ is an alpha interferon indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenect |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | sterile, white to off-white lyophilized powder |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | The recommended starting dose is 6 mcg/kg/week subcutaneously for 8 doses, followed by 3 mcg/kg/week subcutaneously for up to 5 years. Premedicate with acetaminophen 500 to 1000 mg orally 30 minutes prior to the first dose of SYLATRON and as needed for subsequent doses. The recommended starting doses of SYLATRON in patients with moderate or severe renal impairment or end-stage renal disease (ESRD) are listed in Table 1 [see Use In Specific Populations]. No dose adjustment is needed for patients with a creatinine clearance (CLcr) > 50 mL/min/1.73m². |
| Contraindication | SYLATRON is contraindicated in patients with: A history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b autoimmune hepatitis hepatic decompensation (Child-Pugh score >6 [class B and C]) |
| Side Effects | Headache, joint or muscle pain; nausea, dry mouth, loss of appetite, weight loss; dizziness, sleep problems (insomnia), feeling mildly anxious, depressed, or irritable; or pain, redness, swelling, or irritation where the medicine was injected. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |