Pegasys-Peginterferon Alfa-2A to be used in treatment of adults with chronic hepatitis C who have compensated liver disease and have not been previously treated with interferon alfa.
Treatment of adults with chronic hepatitis C who have compensated liver disease and have not been previously treated with interferon alfa
Peginterferon alfa-2a is a pegylated form of interferon alfa-2a that confers protection against enzymatic degradation and reduces renal clearance, prolonging systemic exposure. Interferons bind to specific receptors on the cell surface, initiating intracellular signaling via a complex cascade of protein-protein interactions leading to rapid activation of gene transcription. Interferon- stimulated genes modulate many biological effects, including the inhibition of viral replication in infected cells, inhibition of cell proliferation, and immunomodulation.
The approval of peginterferon alfa-2a was based on results from three multicenter, randomized, open-label, comparative trials involving more than 1,400 adults with compensated liver disease and detectable hepatitis C virus (HCV) who were not previously treated with interferon. Results from all three studies demonstrated that treatment with peginterferon alfa-2a was significantly more effective than treatment with standard interferon alfa 2a in both cirrhotic and noncirrhotic patients, including those infected with viral genotype 1. Additional study data also suggest that peginterferon alfa-2a plus ribavirin may be superior to standard interferon alfa-2b plus ribavirin for the treatment of patients with chronic hepatitis C. Clinical comparisons between peginterferon alfa-2a and peginterferon alfa-2b are not available.
|Volume of distribution||8-12 L|
|Metabolism||Liver, extent unknown. Due to reduced renal clearance from pegylation, hepatic exposure is greater than with standard interferon alfa-2a|
|Excretion||Urine (extent unknown) Feces (extent unknown)|
|Half-life (mean terminal)||80 hours (5.1 hours for standard interferon alfa-2a)|
Hypersensitivity to peginterferon alfa-2a or any product components
Decompensated hepatic disease
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be closely monitored.
May cause severe cytopenias
Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction have been observed.
May cause or aggravate hypothyroidism and hyperthyroidism
Hyperglycemia, hypoglycemia, and diabetes have been observed.
May cause or exacerbate autoimmune disorders
May cause or aggravate pulmonary disorders
Hemorrhagic/ischemic colitis, sometimes fatal, has been observed.
Pancreatitis, sometimes fatal, has occurred.
The most common adverse effects of peginterferon alfa-2a, seen in 20% to 54% of patients, were headache, fatigue, myalgia, pyrexia, rigors, arthralgia, alopecia, nausea, injection-site reaction, and neutropenia.
Less common adverse effects, seen in 5% to 20% of patients, included insomnia, depression, anorexia, dizziness, diarrhea, abdominal pain, and irritability.
180 mcg (1 ml) once weekly for 48 weeks by subcutaneous administration in the abdomen or thigh
Peginterferon alfa-2a is a conjugate of recombinant alfa-2a interferon and bis-monomethoxy polyethylene glycol (PEG). This pegylation results in a compound that has a much lower clearance from the body and a significantly longer half-life, permitting a weekly dosing frequency. The pegylated product has demonstrated efficacy in the treatment of patients with chronic hepatitis C who have compensated liver disease and have not been previously treated with interferon alfa. It has been shown to be more effective than standard interferon alfa-2a in both cirrhotic and noncirrhotic patients, including patients with the more difficult to treat genotype 1 virus.
Published December 2002. Content based on medical literature and product information available at that time.
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