What is Pegasys (Peginterferon alfa-2a)?

From the Guidelines

Pegasys, a brand name for peginterferon alfa-2a, is typically administered as a subcutaneous injection once weekly at a dose of 180 micrograms for adults, and its use in combination with ribavirin for hepatitis C treatment is supported by guidelines such as those from the American Gastroenterological Association 1.

Key Points

• Pegasys works by stimulating the body's immune system to fight viral infections by interfering with viral replication.
• The pegylation of the interferon molecule extends its half-life in the body, allowing for weekly rather than daily dosing.
• Common side effects include flu-like symptoms (fever, headache, fatigue), injection site reactions, decreased blood cell counts, and psychiatric effects like depression.
• Treatment duration typically ranges from 24 to 48 weeks depending on the virus genotype and patient response, with guidelines suggesting 24 weeks for genotype 6 treatment in combination with ribavirin 1.
• Newer direct-acting antiviral medications have largely replaced interferon-based therapies for hepatitis C due to their improved efficacy and reduced side effect profile.

Administration and Dosage

• The dose for peginterferon alpha-2a is 180 μg subcutaneously once a week 1.
• Ribavirin is to be orally administered 1,000 mg in patients under 75 kg, and 1,200 mg in patients over 75 kg when administered with peg-interferon alpha-2a 1.

Clinical Use

• Pegasys is used to treat chronic hepatitis C and certain types of hepatitis B infections.
• It is often used in combination with other antiviral medications like ribavirin for hepatitis C treatment.
• For patients with genotype 1, treatment with PEG-IFN alfa and ribavirin for 48 weeks is recommended, while patients with genotypes 2 and 3 can be treated for 24 weeks 1.
• The treatment algorithm for hepatitis B infection also supports the use of peginterferon alfa-2a, especially in genotype A or B patients who are young, lack significant comorbidities, and have no detectable precore or basal core promoter viral mutants 1.

From the FDA Drug Label

A clinical trial evaluated treatment with PEGASYS and COPEGUS in 50 CHC subjects with moderate (creatinine clearance 30 – 50 mL/min) or severe (creatinine clearance less than 30 mL/min) renal impairment or end stage renal disease (ESRD) requiring chronic hemodialysis (HD). In 18 subjects with ESRD receiving chronic HD, PEGASYS was administered at a dose of 135 mcg once weekly Dose reductions and temporary interruptions of PEGASYS (due to PEGASYS-related adverse reactions, mainly anemia) were observed in up to 22% ESRD/HD subjects during treatment; and 17% of these subjects discontinued PEGASYS due to PEGASYS-related adverse reactions. Only one-third of ESRD/HD subjects received PEGASYS for 48 weeks Subjects with severe (n=14) or moderate (n=17) renal impairment received PEGASYS 180 mcg once weekly. PEGASYS discontinuation rates were 36% and 0% in subjects with severe and moderate renal impairment, respectively, compared to 0% discontinuation rate in subjects with normal renal function Based on the pharmacokinetic and safety results from this trial, patients with creatinine clearance less than 30 mL/min should receive a reduced dose of PEGASYS. In addition, patients with any degree of renal impairment should be carefully monitored for laboratory abnormalities (especially decreased hemoglobin) and adverse reactions, and should undergo careful monitoring of creatinine clearance Patients with clinically significant laboratory abnormalities or adverse reactions which are persistently severe or worsening should have therapy withdrawn [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].

The Pegasys drug is administered subcutaneously, and the dosage may vary depending on the patient's condition.

• For patients with end-stage renal disease (ESRD), the dose is 135 mcg once weekly.
• For patients with severe renal impairment, the dose is 180 mcg once weekly, but the discontinuation rate is 36%.
• For patients with moderate renal impairment, the dose is 180 mcg once weekly, with a 0% discontinuation rate.
• Patients with any degree of renal impairment should be carefully monitored for laboratory abnormalities and adverse reactions. The information provided is based on the study 2.

From the Research

Pegasys Drug Overview

• Pegasys, also known as peginterferon alfa-2a (40KD), is a medication used to treat patients with chronic hepatitis C 3, 4.
• It has improved pharmacokinetics compared to conventional interferon alfa, providing sustained therapeutic plasma levels and can be administered once weekly 3.

Efficacy of Pegasys

• Pegasys has been shown to be more effective than interferon alfa-2a in patients with chronic hepatitis C, including those with cirrhosis 3, 4.
• The combination of Pegasys and ribavirin has been found to produce significantly higher sustained responses than interferon alfa-2b and ribavirin in patients with chronic hepatitis C 3, 5.
• Pegasys has also been shown to be effective in patients infected with viral genotype 1 and those with liver cirrhosis 4, 6.

Safety and Tolerability of Pegasys

• Pegasys is well tolerated when given alone or in combination with ribavirin 3, 5.
• The overall safety profiles of Pegasys and interferon alfa-2b plus ribavirin are similar, with a lower incidence of influenza-like symptoms and depression in patients receiving Pegasys 5.
• Pegasys has been found to have a less impairing effect on health-related quality of life compared to unmodified interferon alpha-2a 7.

Comparison with Other Treatments

• Pegasys plus ribavirin has been found to be more effective than peginterferon alfa-2b plus ribavirin in treating chronic hepatitis C virus infection 6.
• Pegasys alone has been shown to produce significantly higher sustained virologic responses than interferon alfa-2a alone in patients with chronic hepatitis C virus infection 5.