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.

pharmacology

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

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.

absorption

Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

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).

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.

drug interactions

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 theophylline