Interferon Alfa
Mechanism :
Interferons are a family of naturally occurring small protein molecules that are produced and secreted by cells in response to viral infections or to various synthetic and biological inducers. Two major classes of interferons have been identified (i.e. type-I and type-II). While all alpha interferons have similar biological effects, not all the activities are shared by each alpha interferon. All type-I interferons share common biological activities generated by binding of interferon to the cell-surface receptor, leading to the production of several interferon-stimulated gene products. Type-I interferons induce pleiotropic biologic responses which include antiviral, antiproliferative and immunomodulatory effects, regulation of cell surface major histocompatibility antigen (HLA class I and class II) expression and regulation of cytokine expression.
Indication :
- Chronic active hepatitis B infection
- Chronic active hepatitis C infection
Contraindications :
Interferon is contraindicated in patients with known hypersensitivity to alpha interferons, to E coli-derived products, or to any component of the product. Should not be used in the neonatal-period. Severe pre-existing cardiac disease, severe renal, hepatic or myeloid dysfunction, epilepsy, and/or compromised CNS function are contraindications. Immunosuppressed transplant recipients and patients for whom allogenic bone marrow transplantation is planned or possible in the immediate future, thyroid disease unless well controlled, patients with debilitating conditions, including pulmonary disease, diabetes mellitus prone to ketoacidosis, coagulation disorders, patients with chronic hepatitis B, with a history of congestive heart failure and/or previous or current arrhythmic disorders should be closely monitored. A baseline ECG is advised, with monitoring as appropriate throughout treatment. Cardiac arrhythmias, usually supraventricular, respond to conventional therapy but may necessitate discontinuation of interferon alfa. Adequate hydration must be maintained to prevent fluid depletion and hypotension.
Dosing :
3-10 million units/m² usually 3 times/week for a week and given upto 6 million units/m² thrice a week subcutaneously for 16-24 weeks. Max: 10 million units/dose thrice a week.
Adverse Effect :
The common adverse effects are flu-like symptoms such as fatigue, fever, headache and myalgia. Other adverse effects include nausea, anorexia and rigors. Less common effects include diarrhea, vomiting, asthenia, arthralgia, somnolence, dizziness, alopecia, increased sweating, dry mouth, malaise, altered taste, back pain, insomnia, impaired concentration and hypotension. Abnormalities of liver function, hypo- and hyperthyroidism and ocular adverse effects have occurred rarely.
Interaction :
Narcotic Drugs, Hypnotics and Sedatives: risk of interferon affecting CNS function.
Theophylline: May interfere with oxidative metabolism; concurrent use of drugs metabolised by this route, should be undertaken with caution.
Cimetidine, Phenytoin, Diazepam, Warfarin: Monitor serum theophylline levels.
Cyclophosphamide and Doxorubicin: May reduce the activity of the cytochrome P-450 enzyme system.
Drugs metabolised by this enzyme system should be used with caution due to a risk of enhanced effects and/or toxicity.
Vinblastine or Busulfan: Concurrent administration with it may produce severe myelosuppression.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
20-50 | Dose as in normal renal function Monitor renal function closely |
10-20 | Dose as in normal renal function Monitor renal function closely |
<10 | Use with great caution. |
Dose in Patients undergoing Renal Replacement Therapies
CAPD | Not dialysed. Dose as in GFR<10 mL/min |
HD | Not dialysed. Dose as in GFR<10 mL/min |
HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min |
CAV/VVHD | Not dialysed. Dose as in GFR=10– 20 mL/min |
Hepatic Dose :
Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling. Contraindicated in patients with decompensated liver disease, severe hepatitis or autoimmune hepatitis.
Hepatotoxicity during treatment: Children and Adolescents: Permanently discontinue for severe hepatic dysfunction.