1	PEGASYS^® (Peginterferon alfa 2a - 40KD)
2	Indications Chronic Hepatitis C Pegasys is indicated for the treatment of chronic hepatitis C in adults patients who are positive for serum HCV-RNA, including patients with compensated cirrhosis and or co-infected with clinically stable HIV. Chronic Hepatitis B Pegasys is indicated for the treatment of both HBeAg-positive and HBeAg-negatiev chronic hepatitis B in non-cirrhotic and cirrhotic adult patients with compensated liver disease and evidence of viral replication and liver inflammation
3	PEGASYS^®: large, branched 40KD PEG attached by stable bonds Large PEG (40KD) Branched, not linear Stable amide bond Accessibility to interferon alfa receptor maintained Increased serum half-life Small volume of distribution
4	PEGASYS^® maintains consistent plasma levels over a week
5	PEGASYS^® (Peginterferon Alfa-2a [40KD]) Fixed Dose
6	Summary of pharmacokinetics (PK)
7	Efficacy
8	Sustained Virologic Response (ITT Population)
9	Sustained Virologic Response by Genotype (ITT Population)
10	PEGASYS and COPEGUS: increasing SVR rates in all genotypes
11	Pegasys and renal impairment
12	Background There is a higher prevalence of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) than in the general population¹ Patients with ESRD and chronic hepatitis C are at an increased risk of disease progression and decreased graft survival after transplantation Eradication of HCV can increase eligibility for kidney transplantation and improve outcomes Thus, effective treatment for chronic hepatitis C in patients with ESRD is urgently needed
13	Background Conventional interferon has not been well tolerated in patients with ESRD on haemodialysis¹ and ribavirin is contraindicated in such patients Monotherapy with pegylated interferon is the most appropriate therapy for these individuals but the recommended doses are lower than the standard dose used in patients with normal renal function²
14	End-stage Renal Disease HCV infects 10–20% of all end-stage renal disease (ESRD) patients ESRD patients have impaired drug absorption, distribution, metabolism and clearance leading to increase in adverse events high discontinuation rates (up to 50%) RBV contraindicated Can PEGASYS^® (40KD) be used to improve the risk: benefit ratio in these patients?
15	Patients with renal impairment Renal impairment is associated with slightly decreased CL/F and prolonged half-life. In patients with ESRD, a starting dose of 135 micrograms should be used. Regardless of the starting dose or degree of renal impairment, patients should be monitored and appropriate dose reductions of Pegasys during the course of therapy should be made in the event of adverse event
16	Renal Impairment
17	Safety Profile
18	Possible side effects of interferon treatment Flu-like symptoms Fever, chills Headache Fatigue or astheniaarthralgia Myalgia, arthralgia Nausea Anorexia Diarrhoea Psychiatric symptoms Depression Insomnia Alopecia Injection-site reaction Leukopenia Thyroiditis Autoimmunity Thrombocytopenia
19	Possible side effects of ribavirin treatment Haemolytic anaemia Teratogenicity Cough and dyspnoea Rash and pruritus Insomnia Anorexia
20	Contraindications Pegasys in contraindicated in the case of: Hypersensitivity to the active substance, to alpha interferon, or to any of the excipients Autoimmune hepatitis Severe hepatic dysfunction or decompensated cirrhosis of the liver Neonates and young children up to 3 years old, because of the excipient benzyl alcohol A history of sever pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months Pregnancy and lactation Initiation of Pegasys is contraindicated in HIV-HCV patients with cirrhosis and a Child-Pugh score ≥ 6
21	Summary Efficacy Better efficacy in all patients’ subgroups Tolerability Better adherence to treatment Ease of use Fixed dose – no need for dose adjustment in: Weight differences Elderly Renal impairment (CrCl>20)