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Pegasys (Peginterferon alfa-2a)

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  • INDICATIONS AND USAGE

    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.

  • DOSAGE AND ADMINISTRATION

    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

    PEGASYS Hematological Dose Modification Guidelines

    Taken from Table 8 in the full prescribing information

    Laboratory Values Reduce PEGASYS Dose to: Discontinue PEGASYS if:
    ANC ≥750/mm3
    ANC <750/mm3
    Maintain 180 µg
    Reduce to 135 µg
    ANC <500/mm3, treatment should be suspended until ANC values return to more than 1000/mm3
    Reinstitute at 90 µg and monitor ANC
    Platelet≥50,000/mm3
    Platelet <50,000/mm3
    Maintain 180 µg
    Reduce to 90 µg
    Platelet count <25,000/mm3

    Psychiatric: Depression

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

    Taken from Table 9 in the full prescribing information

    Depression
    Severity
    Initial Management
    (4-8 weeks)
    Depression
      Dose
    modification
    Visit
    schedule
    Remains
    stable
    Improves Worsens
    Mild No change Evaluate once weekly by visit and/or phone; Continue weekly visit schedule Resume normal visit schedule (See moderate or severe depression)
    Moderate Decrease PEGASYS dose to 135 µg (in some cases dose reduction to 90 µg may be needed) Evaluate once weekly (office visit at least every other week) Consider psychiatric consultation. Continue reduced dosing If symptoms improve and are stable for 4 weeks, may resume normal visit schedule. Continue reduced dosing or return to normal dose (See severe depression)
    Severe Discontinue PEGASYS permanently Obtain immediate psychiatric consultation Psychiatric therapy necessary

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

    COPEGUS

    COPEGUS Dosage Modification Guidelines

    Taken from Table 10 in the full prescribing information

    Laboratory Values Reduce Only COPEGUS Dose to 600 mg/day* if: Discontinue COPEGUS if:
    Hemoglobin in patients with no cardiac disease <10 g/dL <8.5 g/dL
    Hemoglobin in patients with history of stable cardiac disease ≥2 g/dL decrease in hemoglobin during any 4 week period treatment <12 g/dL despite 4 weeks at reduced dose

    * One 200 mg tablet in the morning and two 200 mg tablets in the evening.

    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.

    PEGASYS and COPEGUS Dosing Recommendations

    Taken from Table 7 in the full prescribing information

    Genotype PEGASYS Dose COPEGUS Dose Duration
    Genotypes 1, 4 180 µg <75 kg = 1000 mg
    ≥75 kg = 1200 mg
    48 weeks
    48 weeks
    Genotypes 2, 3 180 µg 800 mg 24 weeks

    Genotypes 2 and 3 showed no increased response to treatment beyond 24 weeks (see Table 3). Data on genotypes 5 and 6 are insufficient for dosing recommendations.

  • ADVERSE REACTIONS

    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.

    Adverse Reactions Occurring in ≥ 5% of Patients in Chronic Hepatitis C Clinical Trials (Pooled Studies 1, 2, 3, and Study 4)

    Taken from Table 6 in the full prescribing information

      CHC Monotherapy
    (Pooled Studies 1-3)
    CHC Combination Therapy Study 4
    Body System PEGASYS 180 µg 48 week† ROFERON-A*† PEGASYS 180 µg +
    1000 mg or 1200 mg COPEGUS
    48 week**
    intro® A + 1000
    mg or 1200 mg
    REBETOL® 48 week**
      N=559 N=554 N=451 N=443
      % % % %
    Application Site Disorders        
    Injection site reaction 22 18 23 16
    Endocrine Disorders        
    Hypothyroidism 3 2 4 5
    Flu-like Symptoms and Signs        
    Fatigue/Asthenia 56 57 65 68
    Pyrexia 37 41 41 55
    Rigors 35 44 25 37
    Pain 11 12 10 9
    Gastrointestinal
    Nausea/Vomiting
    Diarrhea
    Abdominal pain
    Dry mouth
    Dyspepsia
    24
    16
    15
    6
    <1
    33
    16
    15
    3
    1
    25
    11
    8
    4
    6
    29
    10
    9
    7
    5
    Hematologic‡        
    Lymphopenia 3 5 14 12
    Anemia 2 1 11 11
    Neutropenia 21 8 27 8
    Thrombocytopenia 5 2 5 <1
    Metabolic and Nutritional        
    Anorexia 17 17 24 26
    Weight decrease 4 3 10 10
    Musculoskeletal, Connective Tissue and Bone        
    Myalgia 37 38 40 49
    Arthralgia 28 29 22 23
    Back pain 9 10 5 5
    Neurological        
    Headache 54 58 43 49
    Dizziness (excluding vertigo) 16 12 14 14
    Memory impairment 5 4 6 5
    Resistance Mechanism Disorders        
    Overall 10 6 12 10
    Psychiatric
    Irritability/Anxiety/
    Nervousness
    Insomnia
    Depression
    Concentration impairment
    Mood alteration
    19
    19
    18
    8
    3
    22
    23
    19
    10
    2
    33
    30
    20
    10
    5
    38
    37
    28
    13
    6
    Respiratory, Thoracic and Mediastinal        
    Dyspnea 4 2 13 14
    Cough 4 3 10 7
    Dyspnea exertional <1 <1 4 7
    Skin and Subcutaneous Tissue        
    Alopecia 23 30 28 33
    Pruritus 12 8 19 18
    Dermatitis 8 3 16 13
    Dry skin 4 3 10 13
    Rash 5 4 8 5
    Sweating increased 6 7 6 6
    Eczema 1 1 5 4
    Visual Disorders        
    Vision blurred 4 2 5 2
    • † Pooled studies 1, 2, and 3
       * Either 3 MIU or 6/3 MIU of ROFERON-A
    • **Study 4
    • ‡ Severe hematologic abnormalities (lymphocyte <0.5 x 109/L; hemoglobin <10 g/dL;
    • neutrophil <0.75 x 109/L; platelet <50 x 109/L).

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

  • PREGNANCY CATEGORY C - PEGASYS

    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.

  • PREGNANCY CATEGORY X - COPEGUS

    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).