1. Interferon Alfa-2a, Recombinant
Drugbank ID : DB00034
Protein chemical formula : C860H1353N227O255S9
Protein average weight :
Half life : The IM half-life of interferon alfa-2a is 6 hours to 8 hours; the half-life for IV infusion is 3.7 hours to 8.5 hours (mean 5.1 hours).

2. Description : Indication : Pharmacodynamics :
Interferon a (human leukocyte protein moiety reduced). A type I interferon consisting of 165 amino acid residues with lysine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent. An oral form is being developed by Amarillo Biosciences.
Indication :
For the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia. Also for the treatment of oral warts arising from HIV infection.
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.

3. Mechanism of action : Absorption :
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.
Absorption :
Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

4. Volume of distribution :
Route of Elimination :
Alpha-interferons are totally filtered through the glomeruli and undergo rapid proteolytic degradation during tubular reabsorption, rendering a negligible reappearance of intact alfa interferon in the systemic circulation.
Volume of distribution :
0.223 to L/kg [healthy people]
Clearance :
* mL/min/kg [healthy]

5. Toxicity :
Interferon alfa-2 may cause serious adverse effects such as anemia; autoimmune diseases, including vasculitis, arthritis, hemolytic anemia, and erythematosus syndrome; cardiotoxicity; hepatotoxicity; hyperthyroidism or hypothyroidism; transient ischemic attacks; leukopenia; neurotoxicity; peripheral neuropathy; and thrombocytopenia. Some lesser side effects that may not need medical attention include blurred vision, change in taste or metallic taste, cold sores or stomatitis, diarrhea, dizziness, dry mouth, dry skin or itching, flu-like syndrome, increased sweating, leg cramps, loss of appetite, nausea or vomiting, skin rash, unusual tiredness, weight loss, and partial loss of hair.

6. Drug Interaction: Targets : Affected organisms :
Aminophylline : Interferon increases the effect and toxicity of theophylline
Dyphylline : Interferon increases the effect and toxicity of theophylline
Oxtriphylline : Interferon increases the effect and toxicity of theophylline
Theophylline: Interferon increases the effect and toxicity of theophyllineFood Interactions
Targets :
Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2
Affected organisms :
Humans and other mammals .

7. Patents : Sequence : Country Patent Number Approved Expires
Canada
Sequence :
CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE

8. Brands : Roferon A
Company : Hoffmann-La Roche Inc
Description : Roferon-A (interferon alfa-2a, recombinant) is manufactured by recombinant DNA technology that employs a genetically engineered Escherichia coli bacterium containing DNA that codes for the human protein. Interferon alfa-2a, recombinant is a highly purified protein containing 165 amino acids, and it has an approximate molecular weight of 19,000 daltons. Fermentation is carried out in a defined nutrient medium containing the antibiotic tetracycline hydrochloride, 5 mg/L. However, the presence of the antibiotic is not detectable in the final product.
Used for/Prescribed for : for the treatment of chronic hepatitis C and hairy cell leukemia in patients 18 years of age or older. In addition, it is indicated for chronic phase, Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients who are minimally pretreated (within 1 year of diagnosis).
Formulation : 3 million IU (11.1 mcg/0.5 mL) Roferon-A (interferon alfa-2a, recombinant) per syringe — The solution is colorless and each 0.5 mL contains 3 MIU of Interferon alfa-2a, recombinant, mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a preservative and mg ammonium acetate
Form : solution
Route of administration : subcutaneous injection

9. Dosage : The recommended dosage of Roferon-A (interferon alfa-2a, recombinant) for the treatment of chronic hepatitis C is 3 MIU three times a week (tiw) administered subcutaneously for 12 months (48 to 52 weeks). As an alternative, patients may be treated with an induction dose of 6 MIU tiw for the first 3 months (12 weeks) followed by 3 MIU tiw for 9 months (36 weeks). For Chronic Myelogenous Leukemia pateints the recommended initial dose of Roferon-A (interferon alfa-2a, recombinant) is 9 MIU daily administered as a subcutaneous injection. For Hairy cell leukimia The induction dose of Roferon-A (interferon alfa-2a, recombinant) is 3 MIU daily for 16 to 24 weeks, administered as a subcutaneous injection. The recommended maintenance dose is 3 MIU, tiw. Dose reduction by one-half or withholding of individual doses may be needed when severe adverse reactions occur. The use of doses higher than 3 MIU is not recommended in hairy cell leukemia. Contraindication : Hypersensitivity to Roferon-A (interferon alfa-2a, recombinant) or any of its components, Autoimmune hepatitis, Hepatic decompensation (Child-Pugh class B and C) before or during treatment Side effects : Injection site reactions (pain/swelling/redness), headache, tiredness, diarrhea, upset stomach, loss of appetite, back pain, dizziness, dry mouth, taste changes, nausea, or vomiting may occur. Tooth and gum problems may sometimes occur during treatment. Having a dry mouth can worsen this side effect. Drug interaction : Roferon-A (interferon alfa-2a, recombinant) has been reported to reduce the clearance of theophylline. Synergistic toxicity has been observed when Roferon-A (interferon alfa-2a, recombinant) is administered in combination with zidovudine (AZT)

10. References : http://www. fda. gov/downloads/Drugs/DrugSafety/ucm111340