Interferons (IFNs) are small, secreted glycoproteins and members of the cytokine family of proteins.
IFNs have activity against Hepatitis B (HBV), HCV, HDV, human papilloma virus (HPV), Herpes simplex viruses (HSV) 1 and 2, cytomegalovirus (CMV), vesicular stomatitis virus (VSV), human immunodeficiency virus (HIV), poliovirus, rhinoviruses, adenoviruses, coronaviruses and vaccinia.
Interferons inhibit varying stages of viral replication including viral entry, uncoating, mRNA synthesis and protein synthesis. IFNs have profound immunomodulatory properties. The immune response to IFN-alpha appears to be critical to clearance of hepatitis B and C infection.
In many chronic infections, viruses evade the immune response by mutation of viral peptides, which can bind HLA and T-lymphocyte receptor but do not activate the T cell.
Interferons induce cell surface proteins including Class I (all IFNs) and Class II (IFN-gamma only), beta-2 microglobulin, growth factors and receptors, the Fc family of receptor proteins and complement components. They also enhance natural killer cell function as well as T lymphocyte and macrophage activation.
Interferon-alpha is well absorbed after subcutaneous or intramuscular administration, with a bioavailability greater than 80%. The bioavailability of peginterferon alpha-2a is 61%. Interferon-alpha volume of distribution has been reported to range from 12-40L, with a mean of 31L or 0.4L/kg in healthy volunteers. Pegylation of interferon-alpha reduces the volume of distribution to about 8-20L. Pegylation also decreases the clearance of interferon, thus, increasing the elimination half-life. Total body clearance of interferon-alpha is nearly twice the glomerular filtration rate, suggesting active tubular secretion, renal catabolism, or extrarenal elimination.
The most common adverse effects are a flu-like syndrome characterized by fever, fatigue or malaise, myalgia, chills, headache, and arthralgia. Other adverse effects include neutropenia, thrombocytopenia, anemia, fatigue, headache, irritability, anxiety, dizziness, nausea, vomiting, diarrhea, edema, tachycardia, chest pain, flushing, diaphoresis, proteinuria and alopecia.
Interferon alfa-2a:
Prefilled syringe solution for injection – 3 million units/0.5ml, 6 million units/0.5ml, 9 million units/0.5ml
Interferon alfa-2b:
Powder for infection – 10 million IU, 18 million IU, 50 million IU
Vials for injection –10 million IU, 18 million IU, 25 million IU
Multidose Pen Solution for Injection – 6 doses of 3 million IU (22.5 million IU/1.5ml), 6 doses of 5 million IU (37.5 million IU/1.5ml), 6 doses of 10 million IU (75 million IU/1.5ml)
Interferon alfa-n3:
Solution for injection – 5000000 units/ml
Interferon alfacon-1:
Solution for injection – 15mcg/0.5ml, 9mcg/0.3ml
Interferon beta-1a:
Powder for injection – 30mcg/ml
Solution for Injection in Prefilled Syringes – 30mcg/0.5ml
Interferon beta -1b:
Powder for Injection – 0.3mg/1.2ml (0.25mg/ml)
Interferon gamma-1b:
Solution for Injection – 100mcg (2 million IU)/0.5ml
Peginterferon alfa-2a: 180mcg/ml vials, 180mcg/0.5ml prefilled syringes
Peginterferon alfa-2b: 50mcg/0.5ml, 80mcg/0.5ml, 120mcg/0.5ml, and 150mcg/0.5ml vials for injection. 50mcg/0.5ml, 80mcg/0.5ml, 120mcg/0.5ml, 150mcg/0.5ml Redipen.
Hepatitis C:
Genotype 1: Pegylated Interferon-2a 180mcg/week SC x 48 weeks
Pegylated Interferon-2b 1.5mcg/kg/week SC x 48 weeks
Genotype 2,3: Interferon alpha 3 million units SC three times/week x 24 weeks
Pegylated Interferon-2a 180mcg/week SC x 24 weeks
Pegylated Interferon-2b 1.5mcg/kg/week SC x 24 weeks
Adult Hepatitis B: Interferon alpha 5 million units daily or 10 million units three times/week x 16 weeks
Pegylated Interferon-2a 180mcg/week SC x 24-48 weeks
Pediatric Hepatitis B: Interferon alpha 6 million units/m2 SC three times/week x 16 weeks
Condyloma Acuminata: Interferon alpha 2b- 1 million units via intra-lesion injection three times/week x 3 weeks
Interferon beta – 1 million units via intra-lesion injection three times/week x 3 weeks
Genital Herpes: Interferon alpha 6 million units SC x 1 to 3 days. Doses may range from 6-18 million units.
AIDS-Related Kaposi’s Sarcoma: 30 million units/m2 SC or IM for 16 weeks or until no further evidence of tumor
Chronic granulomatous disease: Interferon gamma-1b 50mcg/m2 SC three times a week.
Hairy Cell Leukemia: Interferon alfa-2b: 3 million IU SC daily x16-24 weeks
Malignant melanoma: Interferon alfa-2a: 20 million IU/m2 IV over 20 minutes 5 days/week x4 weeks.
Multiple sclerosis Interferon beta-1a: 30mcg IM QWeek
Interferon beta-1b: 0.25mcg SQ every other day
Renal Impairment: Caution should be exercised in patients with severe renal insufficiency, although no specific dose adjustments exist.
Hepatic Impairment: No dose adjustment necessary
Depression and suicidal behavior including suicidal ideation, suicidal attempts and suicides have been reported in association with alfa interferons.
There are drug interactions between interferons and myelosuppressive drugs, drugs metabolized by the CYP450 enzyme system and drugs with CNS or cardiac toxicity.
Category C: Risk unknown. Human studies inadequate.
CBC, LFT’s and TSH should be monitored regularly while a patient is on interferon. For hepatitis treatment, prior to starting therapy a liver biopsy and an eye examination should be done and blood glucose, anti- nuclear antibody and urine protein should be checked.
Roferon® A/Hoffmann La Roche Inc
Intron® A, Intron® A Multidose Pen /Schering Corp
Alferon® N/Interferon Sciences Inc
Infergen®/Amgen Inc, Intermune Inc
Avonex®/Biogen Inc
Rebif®, Rebif® Titration Pack/Serono Inc
Betaseron®/Berlex Laboratories Inc
Actimmune®/Intermune Inc
Peg-Intron
Pegasys