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| Primary information |
|---|
| ID | 10379 |
| Therapeutic ID | Th1058 |
| Protein Name | Interferon alfacon-1 |
| Sequence | >Th1058_Interferon_alfacon-1
MCDLPQTHSLGNRRALILLAQMRRISPFSCLKDRHDFGFPQEEFDGNQFQKAQAISVLHEMIQQTFNLFSTKDSSAAWDESLLEKFYTELYQQLNDLEACVIQEVGVEETPLMNVDSILAVKKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSTNLQERLRRKE
|
| Molecular Weight | 19343 |
| Chemical Formula | C860H1353N227O255S9 |
| Isoelectric Point | 5.99 |
| Hydrophobicity | -0.336 |
| Melting point | 61 |
| Half-life | 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys. |
| Description | Recombinant type-I Interferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced), composed of 165 amino acid residues with R at position 23. It resembles leukocyte secreted interferon. Widely used as an antiviral or antineoplastic agent. |
| Indication/Disease | For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma. |
| 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 | Interferon alpha 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 | There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally. |
| Metabolism | NA |
| Absorption | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. |
| NA |
| Clearance | NA |
| Categories | Adjuvants, Immunologic, Alfa Interferons, Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antineoplastic and Immunomodulating Agents, Antiviral Agents, Biological Factors, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Immunosuppressive Agents, Intercellular Signaling Peptides and Proteins, Interferon alpha, Interferon Type I, Interferons, Myelosuppressive Agents, Peptides, Proteins |
| Patents Number | CA1341567 |
| Date of Issue | 19-Feb-2008 |
| Date of Expiry | 19-Feb-2025 |
| Drug Interaction | Zidovudine, The interferon increases the effect and toxicity of zidovudine |
| Target | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 |
| Brand Name | INFERGEN |
| Company | Kadmon Pharmaceuticals, LLC., Valeant Pharmaceuticals, Inc., Three Rivers Pharmaceuticals Llc |
| Brand Description | Kadmon Pharmaceuticals, LLC., Valeant Pharmaceuticals, Inc., Three Rivers Pharmaceuticals Llc |
| Prescribed For | INFERGEN (interferon alfacon-1) is indicated for treatment of chronic hepatitis C in patients 18 years of age or older with compensated liver disease. |
| Chemical Name | NA |
| Formulation | single-use vials containing 9 mcg and 15 mcg interferon alfacon-1 at a fill volume of 0.3 mL and 0.5 mL, respectively. INFERGEN vials contain 0.03 mg/mL interferon alfacon-1, sodium chloride (5.9 mg/mL), and sodium phosphate (3.8 mg/mL) in Water for Injection, USP. |
| Physical Appearance | INFERGEN is a Sterile, clear, colorless, preservative-free liquid |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | The recommended dose of INFERGEN monotherapy for the initial treatment of chronic HCV infection is 9 mcg administered three times a week as a single subcutaneous injection for 24 weeks. |
| Contraindication | contraindicated in patients with hepatic decompensation; autoimmune hepatitis; known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis to interferon alphas or to any component of the product. |
| Side Effects | INFERGEN alone or in combination with ribavirin causes a broad range of serious adverse reactions; |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |