Chronic Hepatitis C

PEGASYS, peginterferon alfa-2a, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C (CHC) virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Efficacy has been demonstrated in subjects with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and in subjects with clinically stable HIV disease and CD4 count greater than 100 cells/mm³.

The following points should be considered when initiating therapy with PEGASYS and COPEGUS:

• Use of PEGASYS monotherapy is not recommended for treatment of CHC unless a patient has a contraindication to or significant intolerance to ribavirin. Combination therapy provides substantially better response rates than monotherapy [see Clinical Studies].
• Safety and efficacy has not been demonstrated for treatment longer than 48 weeks.
• The safety and efficacy have not been established in liver or other organ transplant recipients [see Use In Specific Populations].

Chronic Hepatitis B

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.

PEGASYS is administered by subcutaneous injection in the abdomen or thigh.

Chronic Hepatitis C

PEGASYS Monotherapy

The recommended dose of PEGASYS monotherapy for chronic hepatitis C is 180 meg (1.0 mL vial or 0.5 mL prefilled syringe) once weekly for 48 weeks.

PEGASYS/COPEGUS Combination Therapy

The recommended dose of PEGASYS when used in combination with ribavirin for chronic hepatitis C is 180 meg (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 Table 1).

The daily dose of COPEGUS is 800 mg to 1200 mg administered orally in two divided doses.

COPEGUS should be taken with food.

Table 1: PEGASYS and COPEGUS Dosing Recommendations

Chronic Hepatitis C with HIV Coinfection

PEGASYS Monotherapy: The recommended dose of PEGASYS monotherapy for chronic hepatitis C in patients coinfected with HIV is 180 meg (1.0 mL vial or 0.5 mL prefilled syringe) once weekly for 48 weeks.

PEGASYS/COPEGUS Combination Therapy: The recommended dose when used in combination with ribavirin is PEGASYS 180 meg once weekly and COPEGUS 800 mg orally daily given in two divided doses for a total of 48 weeks, regardless of genotype.

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

Chronic Hepatitis B

PEGASYS Monotherapy: The recommended dose of PEGASYS monotherapy for hepatitis B is 180 meg (1.0 mL vial or 0.5 mL prefilled syringe) once weekly for 48 weeks.

Dose Modifications

If severe adverse reactions or laboratory abnormalities develop during combination PEGASYS/COPEGUS therapy, the dose should be modified until the adverse reactions abate. If intolerance persists after dose adjustment, PEGASYS/COPEGUS therapy should be discontinued. Table 2, Table 3, and Table 4 provide guidelines for dose modifications and discontinuation of PEGASYS/COPEGUS based on laboratory abnormalities, patient's depression status, and cardiac status.

When dose modification of PEGASYS is required for adverse reactions (clinical and/or laboratory), initial dose reduction to 135 meg (which is 0.75 mL for the vials or adjustment to the corresponding graduation mark for the syringes) is recommended. Dose reduction to 90 meg (which is 0.5 mL for the vials or adjustment to the corresponding graduation mark for the syringes) may be needed if the adverse reaction persists or recurs. Following improvement of the adverse reaction, re-escalation of the dose may be considered [see WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS].

Table 2: PEGASYS Hematological Dose Modification Guidelines

Table 3: Guidelines for Modification or Discontinuation of PEGASYS and for Scheduling Visits for Patients with Depression

Table 4: COPEGUS Dose Modification Guidelines

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

Renal Impairment

In patients with CrCL less than 30 mL/min, including patients with end-stage renal disease requiring hemodialysis, dose reduction to 135 meg PEGASYS is recommended. Signs and symptoms of interferon toxicity should be closely monitored. If severe adverse reactions or laboratory abnormalities develop, the dose of PEGASYS may be reduced to 90 meg until the adverse reactions abate. If intolerance persists after dose adjustment, PEGASYS/COPEGUS therapy should be discontinued.

Renal function should be evaluated in all patients on COPEGUS. The dose of COPEGUS should be reduced for patients with creatinine clearance less than or equal to 50mL/min [see CLINICAL PHARMACOLOGY and COPEGUS Package Insert].

Table 5: Dose Modification for Renal Impairment

Liver Function

If ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be immediately discontinued.

In chronic hepatitis C patients with progressive ALT increases above baseline values, the dose of PEGASYS should be reduced to 135 meg and more frequent monitoring of liver function should be performed. After PEGASYS dose reduction or withholding, therapy can be resumed after ALT flares subside.

In chronic hepatitis B patients with elevations in ALT (greater than 5 x ULN), more frequent monitoring of liver function should be performed and consideration should be given to either reducing the dose of PEGASYS to 135 meg or temporarily discontinuing treatment. After PEGASYS dose reduction or withholding, therapy can be resumed after ALT flares subside.

In patients with persistent, severe (ALT greater than 10 times above the upper limit of normal) hepatitis B flares, consideration should be given to discontinuation of treatment.

Discontinuation of Dosing

Discontinuation of therapy should be considered if the patient has failed to demonstrate at least a 2 logio reduction from baseline in HCV RNA titer by 12 weeks of therapy or undetectable HCV RNA after 24 weeks of therapy [see Clinical Studies].

During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation is observed [see CONTRAINDICATIONS].

Patients should be monitored for serious adverse events, some of which may become life threatening. Patients with persistently severe or worsening signs or symptoms should have their therapy withdrawn [see BOXED WARNING].

Preparation and Administration

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 has been trained in proper injection technique [see illustrated FDA Approved 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.

Discard unused portion of PEGASYS in single-use vials or prefilled syringes in excess of the labeled volume. Use only one vial or prefilled syringe per dose.

Dosage Forms and Strengths

• Vial for single use: 180 mcg/1.0 mL
• Prefilled Syringe for single use: 180 mcg/0.5 mL

Single Use Vial: Each PEGASYS (peginterferon alfa-2a) 180 meg single use, clear glass vial provides 1.0 mL containing 180 meg peginterferon alfa-2a for subcutaneous injection. Each package contains 1 vial (NDC 0004-0350-09).

Prefilled Syringes Monthly Convenience Pack: Four prefilled syringes of PEGASYS (peginterferon alfa-2a), 180 meg single use, graduated, clear glass prefilled syringes, in a box with 4 needles and 4 alcohol swabs (NDC 0004-0352-39). Each syringe is a 0.5 mL (½ cc) volume syringe supplied with a 27-gauge, ½-inch needle with needle-stick protection device.

Storage and Handling

Store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. Vials and prefilled syringes are for single use only. Discard any unused portion.

Disposal Instructions

If home use is prescribed, a puncture-resistant container for the disposal of used needles and syringes should be supplied to the patients. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of any needles and syringes. The full container should be disposed of according to the directions provided by the physician [see FDA Approved Medication Guide].

Manufactured by: Hoffmann-La Roche Inc. 340 Kingsland Street, Nutley,NJ07110-1199. Distributed by: Genentech USA, Inc. A Member of the Roche Group. Revised: 08/2011

Last reviewed on RxList: 8/22/2011
This monograph has been modified to include the generic and brand name in many instances.