Peginterferon Alfa-2B Dosage

Usual Adult Dose for Chronic Hepatitis C

Monotherapy:
1 mcg/kg/week subcutaneously for 1 year administered on the same day of the week

Dosages according to weight:
45 kg or less: 40 mcg subcutaneously once a week
46 to 56 kg: 50 mcg subcutaneously once a week
57 to 72 kg: 64 mcg subcutaneously once a week
73 to 88 kg: 80 mcg subcutaneously once a week
89 to 106 kg: 96 mcg subcutaneously once a week
107 to 136 kg: 120 mcg subcutaneously once a week
137 to 160 kg: 150 mcg subcutaneously once a week

Combination therapy:
Peginterferon alfa-2b 1.5 mcg/kg/week subcutaneously plus ribavirin 800 to 1400 mg orally per day in 2 divided doses

The prescribing information for the specific HCV NS3/4A protease inhibitor should be consulted for information regarding dosing regimen and administration of the protease inhibitor in combination with peginterferon alfa-2b and ribavirin.

Dosages according to weight:
39 kg or less: Peginterferon alfa-2b 50 mcg subcutaneously once a week plus ribavirin 400 mg orally twice a day

40 to 50 kg: Peginterferon alfa-2b 64 mcg subcutaneously once a week plus ribavirin 400 mg orally twice a day

51 to 60 kg: Peginterferon alfa-2b 80 mcg subcutaneously once a week plus ribavirin 400 mg orally twice a day

61 to 65 kg: Peginterferon alfa-2b 96 mcg subcutaneously once a week plus ribavirin 400 mg orally twice a day

66 to 75 kg: Peginterferon alfa-2b 96 mcg subcutaneously once a week plus ribavirin 400 mg orally in the morning and 600 mg in the evening

76 to 80 kg: Peginterferon alfa-2b 120 mcg subcutaneously once a week plus ribavirin 400 mg orally in the morning and 600 mg in the evening

81 to 85 kg: Peginterferon alfa-2b 120 mcg subcutaneously once a week plus ribavirin 600 mg orally twice a day

86 to 105 kg: Peginterferon alfa-2b 150 mcg subcutaneously once a week plus ribavirin 600 mg orally twice a day

106 kg or more: Peginterferon alfa-2b 1.5 mcg/kg/week (calculated based on individual patient weight) subcutaneously plus ribavirin 600 mg orally in the morning and 800 mg in the evening

Duration:
Treatment with peginterferon alfa-2b plus ribavirin of interferon alpha-naive patients:
Genotype 1: 48 weeks
Genotype 2 and 3: 24 weeks

Retreatment with peginterferon alfa-2b plus ribavirin of prior treatment failures: 48 weeks, regardless of HCV genotype

For patients with genotype 1 infection, peginterferon alfa-2b plus ribavirin should be used without an HCV NS3/4A protease inhibitor only if its use is not warranted based on tolerability, contraindications, or other clinical factors.

Usual Adult Dose for Malignant Melanoma

6 mcg/kg/week subcutaneously for 8 doses followed by 3 mcg/kg/week subcutaneously for up to 5 years

Premedication with 500 to 1000 mg of oral acetaminophen is recommended 30 minutes prior to the first dose and as needed for subsequent doses.

Usual Adult Dose for Thrombocythemia

(Not approved by FDA)

Study (n=11)
1.5 to 3 mcg/kg subcutaneously once a week
Dose escalation to 4.5 mcg/kg or 6 mcg/kg

Usual Adult Dose for Renal Cell Carcinoma

(Not approved by FDA)

Study (n=31)
6 mcg/kg subcutaneously once a week

Usual Adult Dose for Chronic Myelogenous Leukemia

(Not approved by FDA)

Study (n=31)
6 mcg/kg subcutaneously once a week

Usual Adult Dose for Melanoma - Metastatic

(Not approved by FDA)

Study (n=31)
6 mcg/kg subcutaneously once a week

Usual Adult Dose for Chronic Hepatitis B

(Not approved by FDA)

Study (n=266)
Monotherapy: 100 mcg/week subcutaneously for 31 weeks, then 50 mcg/week subcutaneously from week 32 to 52

Combination therapy (with lamivudine 100 mg/day): 100 mcg/week subcutaneously for 31 weeks, then 50 mcg/week subcutaneously from week 32 to 52

Usual Pediatric Dose for Chronic Hepatitis C

Combination therapy:
3 years or older: Peginterferon alfa-2b 60 mcg/m2/week subcutaneously plus ribavirin 15 mg/kg orally per day in 2 divided doses

Duration:
Genotype 1: 48 weeks
Genotype 2 and 3: 24 weeks

Renal Dose Adjustments

Chronic hepatitis C patients:
Monotherapy:
CrCl 30 to 50 mL/min: Dose should be reduced by 25%.
CrCl 10 to 29 mL/min: Dose should be reduced by 50%.

Combination therapy:
CrCl less than 50 mL/min: Not recommended.

Melanoma patients: Data not available

Liver Dose Adjustments

Moderate or severe hepatic impairment in patients with viral hepatitis, hepatic decompensation (Child-Pugh score greater than 6 [class B and C]): Contraindicated

Dose Adjustments

CHRONIC HEPATITIS C PATIENTS:
Adults:
Monotherapy: Dose reduction is accomplished by reducing the original starting dose of 1 mcg/kg/week to 0.5 mcg/kg/week.

Combination therapy: Dose reduction is accomplished in a 2-step process from the original starting dose of 1.5 mcg/kg/week, to 1 mcg/kg/week, then to 0.5 mcg/kg/week, if needed.

Based on depression (DSM-IV):
Mild: No adjustment recommended.

Moderate: Initial management (4 to 8 weeks) includes reducing peginterferon alfa-2b dose to 0.5 mcg/kg/week for patients on monotherapy or to 1 mcg/kg/week, then to 0.5 mcg/kg/week, if needed, for patients on combination therapy. If symptoms improve and are stable for 4 weeks, recommendations are to continue reduced dosing or return to normal dose.

Severe: Peginterferon alfa-2b plus ribavirin should be permanently discontinued.

Based on laboratory values:
Hgb less than 10 g/dL or greater than 2 g/dL decrease in Hgb during any 4-week period in patients with cardiac disease:
Peginterferon alfa-2b: Dose should be reduced by 50%.

Ribavirin:
First dose reduction:
Patients receiving 1200 mg/day or less: Dose should be reduced by 200 mg/day.
Patients receiving 1400 mg/day: Dose should be reduced by 400 mg/day.

Second dose reduction (if needed): Dose should be reduced by an additional 200 mg/day.

Peginterferon alfa-2b dose should be reduced to 0.5 mcg/kg/week for patients on monotherapy or to 1 mcg/kg/week, then to 0.5 mcg/kg/week, if needed, for patients on combination therapy if any of the following occurs:
WBC greater than 1 x 10(9)/L and less than 1.5 x 10(9)/L
Neutrophils greater than 0.5 x 10(9)/L and less than 0.75 x 10(9)/L
Platelets greater than 25 x 10(9)/L and less than 50 x 10(9)/L

Peginterferon alfa-2b plus ribavirin should be permanently discontinued if any of the following occurs:
Hgb less than 12 g/dL in patients with cardiac disease following reduction of ribavirin dose
Hgb less than 8.5 g/dL
WBC less than 1 x 10(9)/L
Neutrophils less than 0.5 x 10(9)/L
Platelets less than 25 x 10(9)/L

Reduced peginterferon alfa-2b dose (0.5 mcg/kg) for (1 mcg/kg) monotherapy according to weight:
45 kg or less: 20 mcg subcutaneously once a week
46 to 56 kg: 25 mcg subcutaneously once a week
57 to 72 kg: 30 mcg subcutaneously once a week
73 to 88 kg: 40 mcg subcutaneously once a week
89 to 106 kg: 50 mcg subcutaneously once a week
107 to 136 kg: 64 mcg subcutaneously once a week
137 kg or more: 80 mcg subcutaneously once a week

First dose reduction of peginterferon alfa-2b in combination therapy to 1 mcg/kg according to weight:
39 kg or less: 35 mcg subcutaneously once a week
40 to 50 kg: 45 mcg subcutaneously once a week
51 to 60 kg: 50 mcg subcutaneously once a week
61 to 75 kg: 64 mcg subcutaneously once a week
76 to 85 kg: 80 mcg subcutaneously once a week
86 to 104 kg: 96 mcg subcutaneously once a week
105 to 125 kg: 108 mcg subcutaneously once a week
126 kg or more: 135 mcg subcutaneously once a week

Second dose reduction of peginterferon alfa-2b in combination therapy to 0.5 mcg/kg according to weight:
39 kg or less: 20 mcg subcutaneously once a week
40 to 50 kg: 25 mcg subcutaneously once a week
51 to 60 kg: 30 mcg subcutaneously once a week
61 to 75 kg: 35 mcg subcutaneously once a week
76 to 85 kg: 45 mcg subcutaneously once a week
86 to 104 kg: 50 mcg subcutaneously once a week
105 to 125 kg: 64 mcg subcutaneously once a week
126 kg or more: 72 mcg subcutaneously once a week

Discontinuation:
In HCV genotype 1, interferon alfa-naive patients receiving peginterferon alfa-2b (alone or in combination with ribavirin) should discontinue treatment if there is not at least a 2 log10 drop or loss of HCV-RNA at 12 weeks of therapy, or if HCV-RNA levels remain detectable after 24 weeks of therapy. Regardless of genotype, previously treated patients who have detectable HCV-RNA at Week 12 or 24, are highly unlikely to achieve sustained virologic response and discontinuation of therapy is recommended.

The prescribing information for the specific HCV NS3/4A protease inhibitor should be consulted for information regarding discontinuation based on treatment futility.

Pediatrics:
Combination therapy: Dose reduction is accomplished in a 2-step process from the original starting dose of 60 mcg/m2/week, to 40 mcg/m2/week, then to 20 mcg/m2/week, if needed.

Based on depression:
Mild: No adjustment recommended.

Moderate: Initial management (4 to 8 weeks) includes reducing peginterferon alfa-2b to 40 mcg/m2/week, then to 20 mcg/m2/week, if needed. If symptoms improve and are stable for 4 weeks, recommendations are to continue reduced dosing or return to normal dose.

Severe: Peginterferon alfa-2b plus ribavirin should be permanently discontinued.

Based on laboratory values:
Hgb less than 10 g/dL or 2 g/dL or more decrease in Hgb during any 4-week period in patients with preexisting cardiac conditions: Patients should have weekly evaluations and hematology testing. The first ribavirin dose reduction should be to 12 mg/kg/day and the second dose reduction should be to 8 mg/kg/day.

The first peginterferon alfa-2b dose reduction should be to 40 mcg/m2/week and the second dose reduction should be to 20 mcg/m2/week if any of the following occurs:
WBC greater than 1 x 10(9)/L and less than 1.5 x 10(9)/L
Neutrophils greater than 0.5 x 10(9)/L and less than 0.75 x 10(9)/L
Platelets greater than 50 x 10(9)/L and less than 70 x 10(9)/L

Peginterferon alfa-2b plus ribavirin should be permanently discontinued if any of the following occurs:
Hgb less than 8.5 g/dL
WBC less than 1 x 10(9)/L
Neutrophils less than 0.5 x 10(9)/L
Platelets less than 50 x 10(9)/L
Creatinine greater than 2 mg/dL

Discontinuation:
Pediatric patients receiving peginterferon alfa-2b plus ribavirin (excluding those with HCV genotype 2 and 3) should discontinue therapy if their HCV-RNA dropped less than 2 log10 after 12 weeks of treatment compared to pretreatment or if they have detectable HCV-RNA after 24 weeks of treatment.

MELANOMA PATIENTS:
Peginterferon alfa-2b should be permanently discontinued for:
Persistent or worsening severe neuropsychiatric disorders
Grade 4 nonhematologic toxicity
Inability to tolerate a dose of 1 mcg/kg/week
New or worsening retinopathy

Peginterferon alfa-2b should be withheld if any of the following occurs:
Absolute neutrophil count (ANC) less than 0.5 x 10(9)/L
Platelet count less than 50 x 10(9)/L
ECOG performance status (PS) greater than or equal to 2
Nonhematologic toxicity greater than or equal to Grade 3

Peginterferon alfa-2b may be resumed at a reduced dose when all of the following are present:
ANC greater than or equal to 0.5 x 10(9)/L
Platelet count greater than or equal to 50 x 10(9)/L
ECOG PS 0 to 1
Nonhematologic toxicity has completely resolved or improved to Grade 1

Peginterferon alfa-2b dose modifications when starting dose is 6 mcg/kg/week (Doses 1 to 8):
First dose reduction: 3 mcg/kg/week
Second dose reduction: 2 mcg/kg/week
Third dose reduction: 1 mcg/kg/week
If unable to tolerate 1 mcg/kg/week: Permanently discontinue.

Peginterferon alfa-2b dose modifications when starting dose is 3 mcg/kg/week (Doses 9 to 260):
First dose reduction: 2 mcg/kg/week
Second dose reduction: 1 mcg/kg/week
If unable to tolerate 1 mcg/kg/week: Permanently discontinue.

Precautions

Alpha interferons (including peginterferon alfa-2b) 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. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In most cases these disorders resolve after discontinuing peginterferon alfa-2b therapy.

Peginterferon alfa-2b is contraindicated in patients with autoimmune hepatitis and in patients with hepatic decompensation (Child-Pugh score greater than 6 [class B and C]), including cirrhotic chronic hepatitis C (CHC) patients with decompensated liver disease before or during treatment. Clinical status and hepatic function should be monitored closely during treatment, and peginterferon alfa-2b should be stopped at once if decompensation is observed. Hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and lactate dehydrogenase should be monitored at 2 and 8 weeks, and 2 and 3 months after starting peginterferon alfa-2b for adjuvant treatment of melanoma, and the drug should be permanently discontinued if evidence of severe (Grade 3) hepatic injury or hepatic decompensation is observed.

Peginterferon alfa-2b and ribavirin combination therapy is contraindicated in patients with hemoglobinopathies (e.g., sickle cell anemia, thalassemia major), in pregnant women, and in men whose female partners are pregnant.

The manufacturer recommends that patients undergo pregnancy tests prior to the start of combination therapy, then monthly during treatment, and for 6 months following treatment cessation. If pregnancy occurs in a patient or partner of a patient during treatment with peginterferon alfa-2b and ribavirin or during the 6 months after treatment, physicians should report such cases by calling the Ribavirin Pregnancy Registry at 1-800-593-2214 (USA).

Ribavirin causes hemolytic anemia in 10% of peginterferon alfa-2b-treated patients within 1 to 4 weeks of initiation of therapy. Complete blood counts should be obtained before starting treatment, and at 2 and 4 weeks, or more often if necessary. Patients should be closely monitored and may require dose reduction or discontinuation of therapy.

Life-threatening or fatal neuropsychiatric events including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior sometimes directed towards others have been reported in patients with and without a previous psychiatric disorder during peginterferon alfa-2b therapy and follow-up. Psychosis, hallucinations, bipolar disorders, mania, and encephalopathy have been reported in patients treated with alpha interferons. Encephalopathy has been reported with higher doses of peginterferon alfa-2b, usually in elderly patients. Caution is recommended in the treatment of patients with a history of psychiatric disorders. If interferon treatment is started in patients with history or existence of psychiatric condition or with history of substance use disorders, drug screening and periodic health evaluation (including psychiatric symptom monitoring) should be considered. Early intervention for recurrence or development of neuropsychiatric symptoms and substance use is recommended. Patients should be closely monitored and evaluated for signs and symptoms of depression and other psychiatric symptoms and may require dose reduction or discontinuation of therapy. Patients using peginterferon alfa-2b for adjuvant treatment of melanoma should be monitored and evaluated every 3 weeks during the first 8 weeks of therapy and every 6 months thereafter. All patients using peginterferon alfa-2b for adjuvant treatment of melanoma and patients using peginterferon alfa-2b for CHC who develop psychiatric problems (including clinical depression) should be carefully monitored during therapy and for at least 6 months after the last dose. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is observed, peginterferon alfa-2b for CHC should be discontinued and the patient should be followed, with psychiatric intervention as appropriate. In severe cases, peginterferon alfa-2b for CHC should be stopped at once and psychiatric intervention should be started. For persistent severe or worsening psychiatric symptoms or behaviors, peginterferon alfa-2b for adjuvant treatment of melanoma should be permanently discontinued and patients should be referred for psychiatric evaluation. Peginterferon alfa-2b should be permanently discontinued in melanoma patients with persistently severe or worsening signs or symptoms of depression, psychosis, or encephalopathy; however, these disorders may not resolve after stopping the drug.

Patients with ischemic and hemorrhagic cerebrovascular events should be closely monitored and may require dose reduction or discontinuation of therapy.

Peginterferon alfa-2b should be discontinued in patients who develop a severe decrease in neutrophil and/or platelet counts. Close monitoring is recommended.

Close monitoring for signs and symptoms of interferon toxicity, including elevated serum creatinine, is recommended in patients with impaired renal function, and peginterferon alfa-2b dosing should be adjusted accordingly or discontinued. Caution is advised if peginterferon alfa-2b monotherapy is to be used in patients with a CrCl less than 50 mL/min. If renal function decreases during therapy, peginterferon alfa-2b should be discontinued.

Patients on peginterferon alfa-2b, with or without ribavirin, should have hematology and blood chemistry testing before starting therapy and periodically thereafter. TSH levels should be obtained within 4 weeks prior to initiation of peginterferon alfa-2b for adjuvant treatment of melanoma, at 3 and 6 months following initiation, and then every 6 months thereafter while the drug is used.

Patients with hypothyroidism, hyperthyroidism, hyperglycemia, or diabetes mellitus who cannot be effectively treated by medication should not begin peginterferon alfa-2b therapy, and patients who develop these conditions during treatment and cannot be controlled with medication should not continue on peginterferon alfa-2b therapy.

Caution is recommended if peginterferon alfa-2b is to be used in patients with cardiovascular disease. Close monitoring is recommended if the drug is required in patients with a history of myocardial infarction and arrhythmic disorder. Peginterferon alfa-2b with ribavirin should not be used in patients with a history of significant or unstable cardiac disease. Patients with preexisting cardiac abnormalities should have electrocardiograms administered before initiating treatment with peginterferon alfa-2b and ribavirin. For new onset ventricular arrhythmia or cardiovascular decompensation, peginterferon alfa-2b for adjuvant treatment of melanoma should be permanently discontinued.

Peginterferon alfa-2b should be discontinued immediately if signs and symptoms of ulcerative or hemorrhagic/ischemic colitis appear, generally within the first 3 months of therapy.

Peginterferon alfa-2b therapy should be suspended in patients with signs and symptoms suggestive of pancreatitis and discontinued in patients diagnosed with pancreatitis.

Elevated triglycerides levels, which have been reported frequently in patients treated with interferon alfa, should be monitored periodically and managed as clinically necessary. Peginterferon alfa-2b discontinuation should be considered for patients with symptoms of potential pancreatitis.

Peginterferon alfa-2b combination therapy should be suspended in patients with pulmonary infiltrates or pulmonary function impairment. Patients who restart interferon therapy should be monitored closely. Due to fever and other "influenza-like" symptoms associated with administration, peginterferon alfa-2b should be used with caution in patients with debilitating medical conditions, such as those with a history of pulmonary disease.

Decrease or loss of vision, retinopathy including macular edema, retinal hemorrhages and cotton wool spots, retinal artery or vein thrombosis, optic neuritis, papilledema, and serous retinal detachment may be induced or aggravated by treatment with peginterferon alfa-2b or other alpha interferons. All patients should be given an eye examination at baseline. This examination should include assessment of visual acuity and indirect ophthalmoscopy or fundus photography in patients with preexisting retinopathy. Patients with preexisting ophthalmologic disorders should be given periodic ophthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should be given a prompt and complete eye examination. Peginterferon alfa-2b therapy should be discontinued in patients who develop new or worsening ophthalmologic disorders. Melanoma patients who develop new or worsening retinopathy should permanently discontinue the drug.

If serious, acute hypersensitivity reactions or cutaneous eruptions occur, both the immediate discontinuation of peginterferon alfa-2b therapy and the initiation of appropriate medical therapy are recommended. Interruption of treatment is not necessary for transient rashes.

Patients with a history of autoimmune disorders should be closely monitored and may require dose reduction or discontinuation of therapy. Peginterferon alfa-2b should be used with caution in such patients.

Patients with dental/periodontal disorders reported during peginterferon alfa-2b and ribavirin combination therapy should be closely monitored and may require dose reduction or discontinuation of therapy. Brushing teeth thoroughly twice daily and regular dental examinations are recommended.

Caution should be used when administering peginterferon alfa-2b with medications metabolized by CYP450 2C8, 2C9, or 2D6. Patients receiving peginterferon alfa-2b with ribavirin and nucleoside reverse transcriptase inhibitors (NRTI) should be closely monitored for toxicities and NRTI discontinuation should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if clinical toxicities worsen.

The safety and efficacy of treatment beyond 1 year have not been established. The safety and efficacy of peginterferon alfa-2b, alone or in combination with ribavirin, for the treatment of hepatitis C have not been evaluated in liver or other organ transplant recipients. The safety and efficacy of peginterferon alfa-2b with ribavirin for the treatment of patients with HCV coinfected with HIV or HBV have not been determined.

Safety and efficacy for the treatment of chronic hepatitis C have not been established in pediatric patients less than 3 years of age. Safety and efficacy for the adjuvant treatment of melanoma have not been established in pediatric patients (less than 18 years of age).

Dialysis

Chronic hepatitis C patients:
Monotherapy:
Hemodialysis: Dose should be reduced by 50%.
Peritoneal dialysis: Data not available

Combination therapy:
CrCl less than 50 mL/min: Not recommended.

Melanoma patients: Data not available

Other Comments

Patients with previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and/or genotype 1 infection are less likely to benefit from retreatment after a failing course of therapy.

The combination therapy with ribavirin is preferred for treatment of chronic hepatitis C over peginterferon alfa-2b monotherapy unless there are contraindications to or significant intolerance of ribavirin.

Patients who reach their eighteenth birthday while receiving peginterferon alfa-2b plus ribavirin should remain on the pediatric dosing regimen.

The "influenza-like" symptoms associated with the administration of peginterferon alfa-2b may be minimized by the administration of the drug at bedtime or by the use of antipyretics.

See also...