Alpha interferon is available worldwide as at least six dif-Alpha interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant inter-ferent products made by as many pharmaceutical companies.
It is approved for human use in the European Union and the ferons, purified natural leukocyte, and lymphoblastoid interferons. Alpha interferon is administered by subcutaneous or United States for several medical conditions, including hairy cell leukemia, chronic myelogenous leukemia, Kaposi's sar-intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse coma, condylomata acuminata, multiple myeloma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, basal cell effects of alpha interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myal-carcinoma, chronic hepatitis B, and chronic hepatitis C. Both recombinant as well as lymphoblastoid and natural leukocyte gias are common, especially with the initial injections. These early side effects of interferon are predictable and are encoun-alpha interferons have been used to treat chronic hepatitis C virus infection. tered in the majority of patients. These may not require dose modification, but can be problematic for a significant propor-PHARMACOKINETIC DATA tion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10%
Alpha interferon is usually administered by subcutaneous of patients. Neuropsychiatric side effects such as depression or intramuscular injection. Maximum serum levels occur 3 and irritability can be most troublesome; their mechanisms to 12 hours after injection, and serum levels are usually are not well understood. Granulocytes, platelets, and red below the limit of detection by 16 hours. 1 The elimination blood cell counts decrease during treatment, but the decreases half-life of interferon after both subcutaneous and intramusare usually mild, although they can be dose limiting if cell cular injections is 2 to 3 hours, and clearance from the syscounts are low initially. Interferon has important immunotemic circulation is primarily by renal catabolism. After intramodulatory properties, and treatment can induce autoimmune venous administration, serum levels of interferon are phenomena, the most frequent being autoimmune thyroiditis maximal at the end of the infusion, becoming undetectable with either hypothyroidism or hyperthyroidism, especially within 4 hours of the infusion. The elimination half-life is in predisposed patients. Other autoimmune disease can be approximately 2 hours. Measurement of serum concentraaggravated by interferon therapy. Severe and even life-threattions of different preparations of alpha interferon is problemening side effects of interferon occur in 0.1% to 1% of patients; atical because the levels achieved are low after injection of these include thyroid, visual, auditory, renal, and cardiac imtypical doses of 3 to 10 million units (MU). pairment, and pulmonary interstitial fibrosis. Some of these TOXICOLOGY side effects may be irreversible. Higher doses of interferon (above 5 million units three times weekly) cause higher rates
The alpha interferons are generally species specific. 2 Thus, of adverse events than standard doses. Contraindications to animal toxicology studies of human interferon are not very alpha interferon have been recognized. (HEPATOLOGY 1997; meaningful. Toxicology studies using human and animal in-26(Suppl 1):112S-121S.)
terferons have been completed in mice, rats, rabbits, and monkeys. Animal reproduction studies indicate that murine Alpha interferon is a cytokine with pleotropic activities alpha interferon is not teratogenic in rats or rabbits and does that include potent antiviral and antiproliferative effects, as not affect pregnancy, fetal development, or reproductive cawell as many adverse side effects. Binding of type 1 interferon pacity in offspring of treated rats. It is not clear whether to a cell surface receptor leads to the intracellular production these findings can be extrapolated to humans or whether of several gene products. Many of these interferon-induced alpha interferon can cross the placental barrier, but the bulk genes, including 2,5-oligoadenylate synthetase and b2-miof evidence suggests that interferon does not. 2 croglobulin, are accepted surrogate markers for the biological
The mechanisms for clinical toxicity caused by alpha interactivity of interferon. Which of these proteins is responsible feron are poorly understood. Inducible biochemical markers, for the antiviral activities and which for the side effects of such as 2,5-oligoadenylate synthetase activity, correlate alpha interferon in chronic hepatitis C is not known.
well with dose administered and serum concentrations of interferon, but correlate poorly with clinical response and frequency of side effects.