1. Peginterferon alfa-2a Drugbank ID : DB00008
Protein average weight :
Half life : Terminal half life is 80 hours (range 50 to 140 hours).

2. Description : Indication : Pharmacodynamics :
Human interferon 2a, is a covalent conjugate of recombinant alfa-2a interferon with a single branched bis-monomethoxy polyethylene glycol (PEG) chain. The PEG moiety is linked at a single site to the interferon alfa moiety via a stable amide bond to lysine. Peginterferon alfa-2a has an approximate molecular weight of 60,000 daltons. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted into and expressed in Escherichia coli. The resultant protein is 165 amino acids. 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 :
For 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..

3. 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.

4. Drug Interaction: Targets : Affected organisms :
Aminophylline : Interferon increases the effect and toxicity of theophylline
Dyphylline : Interferon increases the effect and toxicity of theophylline
Etravirine : Etravirine (a CYP2C9 substrate), when used concomitantly with peginterferon alfa-2a, may experience a decrease in serum concentration. It is recommended to monitor effectiveness of etravirine therapy.
Oxtriphylline : Interferon increases the effect and toxicity of theophylline
Telbivudine : Co-administration of Peginterferon alpha-2a and Telbivudine may increase the risk of serious peripheral neuropathy.
Theophylline : Interferon increases the effect and toxicity of theophylline
Targets :
Interferon alpha/beta receptor 2,Interferon alpha/beta receptor 1
Affected organisms :
Humans and other mammals

5. Categories : Patents : Sequence : Immunosuppressive Agents
Country Patent Number Approved Expires (estimated)
Canada
Canada
Sequence :
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE

6. Brands : Pegasys
Company : Hoffman-La Roche Inc
Description : PEGASYS, peginterferon alfa-2a, is a covalent conjugate of recombinant alfa-2a interferon (approximate molecular weight [MW] 20,000 daltons) with a single branched bis-monomethoxy polyethylene glycol (PEG) chain (approximate MW 40,000 daltons). The PEG moiety is linked at a single site to the interferon alfa moiety via a stable amide bond to lysine. Peginterferon alfa­2a has an approximate molecular weight of 60,000 daltons. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted into and expressed in Escherichia coli.
Used for/Prescribed for : Pegasys is used to treat chronic hepatitis B or C in adults, and to treat chronic hepatitis C in children who are at least 5 years old. It is often used together with another medication called ribavirin
Formulation : Each vial of 180 mcg/mL peginterferon alfa-2a (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.05 mg), benzyl alcohol (10 mg), polysorbate 80 (0.05 mg), sodium acetate trihydrate (2.62 mg), and sodium chloride (8 mg) at pH 6 ± 0.5.
Form : sterile, preservative-free, colorless to light yellow injectable solution
Route of administration : subcutaneous injection

7. Dosage : Pegasys is usually given once per week
Dosage : Pegasys is usually given once per week. Contraindication : allergic, having failure or autoimmune hepatitis, haemoglobin blood cell disorder as sickle cell anemia or thalessimia. Side effects : Common Pegasys side effects may include: nausea, vomiting, loss of appetite; headache, muscle pain, feeling weak or tired; sleep problems (insomnia); temporary hair loss; or itching, redness, dryness, or swelling where the medicine was injected Drug interaction : A total of 181 drugs (582 brand and generic names) are known to interact with Pegasys (peginterferon alfa-2a) among which 19 major drug interactions (82 brand and generic names), 156 moderate drug interactions (477 brand and generic names) and 6 minor drug interactions (23 brand and generic names).

8. References : http://www. pegasys. com/ http://www. rxlist