PEGASYS, peginterferon alfa-2a, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus 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) and patients with HIV disease that is clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy).

PEGASYS is indicated for the treatment of adult patients with HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation.

There are no safety and efficacy data on treatment of chronic hepatitis C or hepatitis B for longer than 48 weeks. For patients with hepatitis C, consideration should be given to discontinuing therapy after 12 to 24 weeks of therapy if the patient has failed to demonstrate an early virologic response defined as undetectable HCV RNA or at least a 2log10 reduction from baseline in HCV RNA titer by 12 weeks of therapy (see CLINICAL STUDIES).

A patient should self-inject PEGASYS only if the physician determines that it is appropriate and the patient agrees to medical follow-up as necessary and training in proper injection technique has been provided to him/her (see illustrated PEGASYS MEDICATION GUIDE for directions on injection site preparation and injection instructions).

PEGASYS should be inspected visually for particulate matter and discoloration before administration, and not used if particulate matter is visible or product is discolored. Vials and prefilled syringes with particulate matter or discoloration should be returned to the pharmacist.

General

When dose modification is required for moderate to severe adverse reactions (clinical and/or laboratory), initial dose reduction to 135 µg (which is 0.75 mL for the vials or adjustment to the corresponding graduation mark for the syringes) is generally adequate. However, in some cases, dose reduction to 90 µg (which is 0.5 mL for the vials or adjustment to the corresponding graduation mark for the syringes) may be needed. Following improvement of the adverse reaction, re-escalation of the dose may be considered (see WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS in the full prescribing information).

Hematological

Psychiatric: Depression

COPEGUS

Once COPEGUS has been withheld due to a laboratory abnormality or clinical manifestation, an attempt may be made to restart COPEGUS at 600 mg daily and further increase the dose to 800 mg daily depending upon the physician’s judgment. However, it is not recommended that COPEGUS be increased to the original dose (1000 mg or 1200 mg).

PEGASYS and COPEGUS Combination Therapy

The recommended dose of PEGASYS when used in combination with ribavirin for chronic hepatitis C is 180 µg (1.0 mL vial or 0.5 mL prefilled syringe) once weekly. The recommended dose of COPEGUS and duration for PEGASYS/COPEGUS therapy is based on viral genotype(see the table below).

The daily dose of COPEGUS is 800 mg to 1200 mg administered orally in two divided doses. The dose should be individualized to the patient depending on baseline disease characteristics (e.g., genotype), response to therapy, and tolerability of the regimen.

Since COPEGUS absorption increases when administered with a meal, patients are advised to take COPEGUS with food.

Alpha interferons, including PEGASYS (peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see WARNINGS and ADVERSE REACTIONS).

Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see COPEGUS Package Insert for additional information and other WARNINGS).


COPEGUS (ribavirin) monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication (see WARNINGS).

The primary clinical toxicity of ribavirin is hemolytic anemia. The anemia associated with ribavirin therapy may result in worsening of cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with ribavirin (see WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION).

Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple dose half-life of 12 days, and it may persist in non-plasma compartments for as long as 6 months. Ribavirin therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of therapy in both female patients and in female partners of male patients who are taking ribavirin therapy. At least two reliable forms of effective contraception must be utilized during treatment and during the 6-month posttreatment follow-up period (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: Information for Patients, and Pregnancy: Category X).

Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug. Also, the adverse event rates listed here may not predict the rates observed in a broader patient population in clinical practice.

For additional dosing information on adverse events, please see the full prescribing information

PEGASYS has not been studied for its teratogenic effect. Non-pegylated interferon alfa-2a treatment of pregnant Rhesus monkeys at approximately 20 to 500 times the human weekly dose resulted in a statistically significant increase in abortions. No teratogenic effects were seen in the offspring delivered at term. PEGASYS should be assumed to have abortifacient potential. There are no adequate and well-controlled studies of PEGASYS in pregnant women. PEGASYS is to be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. PEGASYS is recommended for use in women of childbearing potential only when they are using effective contraception during therapy.

Ribavirin may cause birth defects and/or death of the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin has demonstrated significant teratogenic and/or embryocidal effects in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of ribavirin. COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO PLANNED INITIATION OF THERAPY. Patients should be instructed to use at least two forms of effective contraception during treatment and for 6 months after treatment has been stopped. Pregnancy testing should occur monthly during COPEGUS therapy and for 6 months after therapy has stopped (see CONTRAINDICATIONS and PRECAUTIONS: Information for Patients and Pregnancy: Category X).