Peginterferon alfa Interferon

Treatment options for viral hepatitis include lamivu-dine, simple interferon alpha, polyethylene glycol-linked interferon (Peginterferon alfa-2a), and ade-fovir and ribavirin. Selected regimes have markedly improved response rates, but relapse is still common. 

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C a randomised trial. Lancet 358 958-965... 

Chronic HCV- In combination with peginterferon alfa-2a for the treatment of adults with chronic HCV infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A). 

The safety and efficacy of ribavirin capsules or oral solution with interferons other than interferon alfa-2b or peginterferon alfa-2b products have not been established. 

Capsules/Tablets/Oral solution - Ribavirin monotherapy is not effective for the treatment of chronic HCV infection. The safety and efficacy of ribavirin capsules and oral solution have only been established when used together with interferon alfa-2b, recombinant as interferon alfa-2b/ribavirin capsule combination therapy or with peginterferon alfa-2b injection. 

Capsules/Tablets/Oral solution-There are significant adverse events caused by ribavirin capsules/interferon alfa-2b or peginterferon alfa-2b therapy, and ribavirin tablets/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. 

Pancreatitis Suspend ribavirin, interferon alfa-2b, peginterferon alfa-2b, or peginterferon alfa-2a therapy in patients with signs and symptoms of pancreatitis and discontinue in patients with confirmed pancreatitis. 

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. 

Renal function impairment- In patients with end-stage renal disease requiring hemodialysis, dose reduction to 135 meg peginterferon alfa-2a is recommended. Closely monitor for signs and symptoms of interferon toxicity. Do not use ribavirin in patients with creatinine clearance less than 50 mL/min. 

Bone marrow toxicity Peginterferon alfa-2a suppresses bone marrow function and may result in severe cytopenias. Ribavirin may potentiate the neutropenia and lymphopenia induced by alpha interferons including peginterferon alfa-2a. Alpha interferons may be associated with aplastic anemia very rarely. 

Ophthaimoiogic disorders Decrease or loss of vision, retinopathy (including macular edema, retinal artery or vein thrombosis), retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema are induced or aggravated by treatment with peginterferon alfa-2a or other alpha interferons. All patients should receive an eye examination at baseline. 

Puimonary disorders Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by peginterferon alfa-2a or alpha interferon therapy. 

Immunogenicity Nine percent of patients treated with peginterferon alfa-2a with or without ribavirin tablets developed binding antibodies to interferon alfa-2a, as assessed by an ELISA assay. The clinical and pathological significance of the appearance of serum neutralizing antibodies is unknown. 

Alpha interferons, including peginterferon alfa-2b, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Closely monitor patients with periodic clinical and laboratory evaluations. Withdraw from therapy patients with persistently severe or worsening signs or symptoms of... 

Pharmacology The biological activity of peginterferon alfa-2b is derived from its interferon alfa-2b moiety. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface and initiate a complex sequence of intracellular events. 

Pegylation of interferon alfa-2b produces a product (peginterferon alfa-2b) whose clearance is lower than that of nonpegylated interferon alfa-2b. When compared to interferon alfa-2b, peginterferon alfa-2b (1 mcg/kg) has an approximately 7-fold lower mean apparent clearance and a 5-fold greater mean half life permitting a reduced dosing frequency. 

Neuropsychiatric events Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior have occurred in patients with and without a previous psychiatric disorder during peginterferon alfa-2b treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with alpha interferons. 

Renal function impairment Closely monitor patients with impairment of renal function for signs and symptoms of interferon toxicity and adjust doses of peginterferon alfa-2b accordingly. Use peginterferon alfa-2b with caution in patients with Ccr less than 50 mL/min. 

Elderly Treatment with alpha interferons, including peginterferon alfa-2b, is associated with CNS, cardiac, and systemic (flu-like) adverse effects. Because these adverse reactions may be more severe in the elderly, exercise caution in the use of interferon alfa-2b in this population. 

Immunogenicity Approximately 2% of patients receiving peginterferon alfa-2b or interferon alfa-2b with or without ribavirin capsules developed low-titer (160 or less) neutralizing antibodies to peginterferon alfa-2b or interferon alfa-2b. 

Organ transplants The safety and efficacy of peginterferon alfa-2b alone or in combination with ribavirin capsules for the treatment of hepatitis C in patients who have received liver or other organ transplants have not been studied. Preliminary data indicate that interferon alpha therapy may be associated with an increased rate of kidney graft rejection. Liver graft rejection also has been reported, but a causal... 

Peginterferon alfa-2a treatment results in more sustained responses than simple interferon alpha, although relapse is not uncommon. Such treatment should generally be avoided in those receiving immunosuppressants and those with decompensated liver disease. Lamivudine, a reverse transscriptase inhibitor is often used in initial treatment and in decompensated liver disease. 

Peginterferon alpha, either peginterferon alfa-2a or peginterferon alfa-2b, with ribavirin is recommended for treatment of those aged 18 years and over who have not previously received an interferon, or who have received such treatment but where response was inadequate. Choice of treatment depends on viral load and genotype. Treatment of patients with coincident HIV infection requires specialist advice. 

Weekly administration of peginterferon alfa-2a equivalent to 3 times weekly administration of interferon alfa-2a for hepatitis C... 

Chronic hepatitis C PO (capsule or oral solution in combination with interferon alfa-2b) 1,000-1,200 mg/day in 2 divided doses. PO (capsules in combination with peginterferon alfa-2b) 800 mg/day in 2 divided doses. PO (tablets in combination with peginterferon alfa-2b) 800-1,200 mg/day in 2 divided doses. Ribavirin with peginterferon alfa-2b requires individualized dosing. 

Hepatitis C therapy interferon alfa-2b/ribavirin peginterferon-2b peginterferon alfa-2b/ribavirin... 

Manns, M.P., J.G. McHntchison, S. Gordon, et al., Peginterferon alfa-2b plus ribavirin compared to interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C a randomized trial. Lancet, 2001. 358 958-65. 

Recommended dosage and monitoring requirements The recommended dose of Roferon-A for chronic hepatitis C is 3 million international units (MIU) three times a week for 12 months. The recommended dose for CML is 9 MIU daily optimal duration of therapy has not been determined. The recommended dose for hairy cell leukemia is 3 MIU daily for 16 to 24 weeks. The recommended dose for AIDS-related Kaposi s sarcoma is 36 MIU daily for 10 to 12 weeks. There are five types of interferon alfa currently available in the United States interferon alfa-2a, peginterferon alfa-2a, interferon alfa-2b, interferon alfacon-1, and interferon alfa n3. Doses are not consistent for these preparations. 

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