Active Ingredient: Recombinant Pegylated Interferon alfa-2a.
Presentation and composition:
1 disposable pre-filled syringe with 1 ml injectable solution contains: Recombinant Interferon alfa-2a (approximate Molecular Weight 20KD) 180 μg attached to a branched-chain Polyethylene Glycol polymer (approximate Molecular Weight 40KD) in a pH adjusted citrated buffer. One syringe solution medium contains sodium chloride, ammonium acetate, benzyl alcohol, polysorbate 80 and water for injection 1 ml.
Pharmacology: Pegaferon is a synthetic analogue of interferon alfa-2a. As a result of attachment of 40KD branched-chain polyethylene glycol polymer to the native molecule, the agonistic effect is more prolonged, the plasma half-life is more prolonged, in-vivo activity is enhanced and immunogenicity and antigenicity is decreased. Following binding to specific cellular receptors, Interferon alfa-2a activates the JAK-STAT signal-transduction pathway that contributes to viral resistance mediated at different stages of viral penetration, Inhibition of protein synthesis in the presence of double-stranded RNA and ameliorate viral infections by exerting direct antiviral effects and by modifying the immune response to infection. After single injection of Pegaferon, plasma levels remain at the therapeutic level for one week.
Therapeutic indications: Treatment of chronic hepatitis C and chronic Hepatitis B.
Posology and method of administration:
Pegaferon is administrated at a fixed dose of 180μg for all patients by subcutaneous injection. Chronic Hepatitis B: The recommended dosage of Pegaferon for both HBeAg-positive and HBeAg-negative chronic hepatitis B is 180μg once weekly by subcutaneous administration in the abdomen or thigh. The recommended duration of therapy is 48 weeks. Chronic Hepatitis C: The recommended dosage of Pegaferon, alone or in combination with Ribavirin, is 180μg once weekly by subcutaneous administration in the abdomen or thigh. The recommended duration of Pegaferon monotherapy is 48 weeks. The Recommended dosage and duration of therapy with Pegaferon plus Ribavirin should be individualized based on patient’s viral genotype and bodyweight.
|Genotype||Weekly Pegaferon dose||Daily Ribavirin dose||Tx Duration|
|Genotype 1, 4||180μg||<75 kg = 1000 mg≥75kg = 1200 mg||48 weeks48 weeks|
|Genotype 2, 3||180μg||800 mg||24 weeks|
The recommended dosage for HCV/HIV co-infection (in combination or without Ribavirin) regardless of viral genotype is 180μg once weekly by subcutaneous administration in the abdomen or thigh. The duration of therapy is 48 weeks.
Contraindications: Pegaferon should not be used in patients with hypersensitivity to Pegaferon or any of its components, autoimmune hepatitis, decompensated cirrhosis with or without HIV co-infection (child-pugh score greater than 6 [class B and C]) before or during treatment, neonates and infants. Pegaferon and Ribavirin combination therapy is additionally contraindicated in patients with hypersensitivity to Ribavirin, pregnant women, men with pregnant female partners, patients with thalassemia major or sickle cell anemia.
Special warnings and precautions for use:
General: Patients should be monitored for the following serious conditions, some of which may become life threaning. Patients with persistently severe or worsening signs or symptoms should have their therapy withdrawn. Pegaferon should be used with caution or avoided alltogether in patients with depression or psychiatric disorders, epilepsy or other CNS diseases. Severe neuropsychiatric reactions may manifest in patients with Pegaferon and include suicide, homocidal ideation, drug addiction and drug overdose. Pegaferon should be used with caution or avoided in patients with renal or hepatic impairment, cardiac disorders, myelosuppression, poorly controled thyroid dysfunction, pulmonary diseases, diabetes mellitus, autoimmune diseases, coagulation disorders, or a history of these conditions. Patients with psoriasis or sarcoidosis have been reported to experience exacerbations during Pegaferon therapy. Although flu-like syndrome is common during Pegaferon therapy, other causes of high or persistent fever must be ruled out, particaularly in patients with neutropenia. Blood counts should be monitored, particularly in patients at high risk of myelosuppression (e.g. dose with hematologic malignancies). Assessment of cardiac function is advised before treatment is started. Ischemic and hemorrhagic cerebrovascular events have been reported in patients treated with interferon alfa-based therapies. Patients receiving Pegaferon who have visual disturbances should receive an eye examination. A base line ocular examination is recommonded before treatment and periodic eye examinations should be performed throughout treatment in patients predisposed to retinopathy, such as those with diabetes mellitus or hypertension. Hepatic and renal function should be monitored during treatment with Pegaferon. Pegaferon should be discontinued in patients with chronic hepatitis who develop liver decompensation. Patients should receive adequate fluids to maintain hydration dirung treatment with pegaferon. Pegaferon may affect ability to drive or operate machinery.
Possible serious side effects: Pegaferon may cause risks to pregnancy, psychological problems including suicidal and hemocidal thoughts, blood problems including neutropenia and thrombocytopenia, autoimmune problems, cardiovascular problems including chest pain and in rare instance heart attack, and hepatic dysfunction. Common but less serious side effects: Pegaferon may induce flu-like syndrome, extreme fatigue, upset stomach, blood sugar problems, skin reactions, temporary hair loss and trouble sleeping.
There are no adequate and well-controled studies of pegylated interferon alfa-2a in pregnant women. Pegaferon should be assued to have abortifacient potential. Pegaferon may be used in pregnancy only if the potential benefits justifies the potential risk to the fetus. In women with childbearing potential, it is recommended that they use effective contraception methods in order to be treated with Pegaferon.
Maximal serum concentrations ( Cmax) occur between 72 to 96 hours post does, and are sustained for up to 168 hours. The Cm and AUC measurements of Interferon alfa-2a (long acting) increase in a does-related manner. Week 48 mean trough concentrations ( 16 ng/ml; range 4 to 28 ) are approximately 2 fold higher than week 1 mean trough concentrations ( 8 ng/ml; range 0 to 15 ). Steady-state serum levels are reached within 5 to 8 weeks of once weekly dosing. The peak to trough ratio at week 48 is approximately 2.0. The mean systemic clearance in healthy subjects given Interferon alpha-2a (long acting) was 94 ml/h, which is approximately 100-fold lower than that for Interferon alpha-2a. The mean terminal half-life after subcutaneous dosing in patients with chronic hepatitis C was 80 hours (range 50 to 140 hours) compared to 5.1 hours (range 3.7 to 8.5 hours) for Interferon alpha-2a. Interferon alpha-2a (long acting) administration yielded similar pharmacokinetics in male and female healthy subjects. The AUC was increased from 1295 to 1663 ng-h/ml in subjects older than 62 years taking 180 180μg Interferon alpha-2a (long acting) but peak concentrations were similar (9 vs. 10 ng/ml ) in those older and younger than 62 years. In patients with end stage renal disease undergoing hemodialysis, there is a 25% to 45% reduction in clearance.