Pegylated interferon

Persons with confirmed chronic hepatitis B should be evaluated for treatment, which may include interferon, pegylated interferon, lamivudine, adefovir dipivoxil, or entecavir. The drug of choice for chronic hepatitis B depends on the patient s past medical history, aminotransferase level, HBV DNA level, and most importantly, HBeAg status. 

At present, pegylated interferon plus ribavirin is the regimen of choice for the treatment of hepatitis C.41 Interferon, pegylated interferon, and ribavirin have significant adverse effects, as discussed below. 

Adverse effects of interferon, pegylated interferon, and ribavirin therapy... 

Brockmeyer NH, Poflhoff A, Bader A, Hochdorfer B, Schlottmann R, Rasokat H, Altmeyer P, Kreuter A (2006) Treatment of condylomata acuminata with pegylated interferon alfa-2b in HIV-infected patients. Eur J Med Res 11 27-32... 

De Rosa EG, Bargiacchi O, Audagnotto S, Garazzino S, Cariti G, Veronese L, Raiteri R, CaUeri G, Di Perri G (2006) The early HCV RNA dynamics in patients with acute hepatitis C treated with pegylated interferon-alpha2b. Antivir Ther 11 165-171 Di Bisceglie A (1997) Hepatitis D virus. Marcel Dekker, NY... 

Erhardt A, Gerlich W, Starke C, Wend U, Donner A, Sagir A, Heintges T, Haussinger D (2006) Treatment of chronic hepatitis delta with pegylated interferon-alpha2b. Liver Int 26 805-810... 

Kozlowski A, Charles SA, Harris JM (2001) Development of pegylated interferons for the treatment of chronic hepatitis C. BioDrugs 15 419 29 Krown SE, AeppU D, Balfour HH Jr (1999) Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol 20 245-254 LaFleur DW, NardeUi B, Tsareva T, Mather D, Feng P, Semenuk M, Taylor K, Buergin M, Chinchilla D, Roshke V, Chen G, Ruben SM, Pitha PM, Coleman TA, Moore PA (2001) Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem 276 39765-39771... 

Niro GA, Rosina F, Rizzetto M (2005b) Treatment of hepatitis D. J Viral Hepat 12 2-9 Niro GA, Ciancio A, Gaeta GB, SmedUe A, Marrone A, OUvero A, Stanzione M, David E, Bran-caccio G, Fontana R, Perri F, AndriuUi A, Rizzetto M (2006) Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 44 713-720... 

Combination Therapy with Ribavirin and Development of Pegylated Interferons... 

The development of pegylated (peg) interferons that possess a sustained absorption, a slower rate of clearance, and a longer half life than unmodified interferons led to further improvement of sustained virologic response rates especially for patients infected with genotype 1 (Fig. 1) (Fried et al. 2002 Manns et al. 2001 Zeuzem et al. 2000). 

HCV-796 is a non-nucleosidic NS5B polymerase inhibitor with potent antiviral activity in vitro. A phase lb study was performed to determine the antiviral activity, pharmacokinetics, and safety of HCV-796 in patients with chronic HCV infection. Maximum antiviral effects were achieved after 4 days of treatment with a mean reduction of HCV-RNA of 1.4 loglOIU/ml. Combination of HCV-796 with pegylated interferon-a led to a greater reduction of viral RNA load (3.3-3.5 loglO lU/ml) after a 14 days treatment interval. 

Interferon alfa is an antiviral agent that is effective in suppressing hepatitis B viral replication. Interferon alfa-2b and pegylated interferon alfa-2a are the only interferon therapies approved for the treatment of chronic hepatitis B. 

Pegylated interferon is interferon that is attached to a polyethylene glycol molecule that increases the half-life of the drug, thus allowing once-weekly dosing versus thrice-weekly administration required for the unmodified formulation. Pegylated interferon is well tolerated and is superior in efficacy to unmodified interferon for the treatment of chronic hepatitis B.26... 

The subcutaneous dose of interferon alfa-2b (Intron A) in patients who are HBsAg-positive is either 5 million units daily (better tolerated) or 10 million units three times weekly. The dose for HBsAg-negative patients is 5 to 6 million units three times weekly. The approved dose for pegylated interferon alfa-2a (Pegasys) for chronic hepatitis B is 180 meg subcutaneously once weekly. Interferon doses may need to be adjusted in patients with renal impairment. 

Individuals with confirmed chronic hepatitis C should be evaluated for treatment with pegylated interferon with or without ribavirin. 

The type and incidence of adverse effects associated with unmodified interferon and pegylated interferon are comparable. Approximately 10% to 30% of patients receiving interferon and/or ribavirin require a dosage reduction or treatment discontinuation to minimize side effects. Patients should be screened for uncommon adverse effects and laboratory abnormalities prior to starting interferon and ribavirin because treatment may exacerbate or worsen some medical conditions. 

Most patients treated with either interferon or pegylated interferon experience flulike symptoms (fevers, chills, rigors, and myalgias). These symptoms may be mild to moderate in severity and usually occur with the first injection and diminish as the treatment continues. The flulike symptoms may be minimized by premedication with acetaminophen or a nonsteroidal anti-inflammatory drug. 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

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