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PegIntron(peginterferon alfa-2b) Powder for Injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use PegIntron safely and effectively. See full prescribing information for PegIntron.
PegIntron (Peginterferon alfa-2b) Injection, Powder for Solution for Subcutaneous Use
Initial U.S. Approval: 2001
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
See full prescribing information for complete boxed warning.
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders. (5)
Use with Ribavirin
Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients. (5.1)
Ribavirin is a potential carcinogen. (5.1, 13.1)
RECENT MAJOR CHANGES
Indications and Usage, Chronic Hepatitis C (1.1) [3/2009]
Dosage and Administration, Combination Therapy (2.1) [5/2009]
Dosage and Administration, PegIntron Monotherapy (2.2) [3/2009]
Dosage and Administration, Dose Reduction (2.3) [5/2009]
Dosage and Administration, Discontinuation of Dosing (2.4) [3/2009]
Contraindications (4) [12/2008]
Warnings and Precautions, Ophthalmologic Disorders (5.5) [8/2009]
Warnings and Precautions, Pulmonary Disorders (5.11) [8/2009]
Warnings and Precautions, Laboratory Tests (5.15) [12/2008]
Warnings and Precautions, Impact on Growth-Pediatric Use (5.18) [12/2008]
Warnings and Precautions, Peripheral Neuropathy (5.19) [8/2009]
INDICATIONS AND USAGE
PegIntron is an antiviral indicated for
Combination therapy with REBETOL (ribavirin):
Chronic Hepatitis C (CHC) in patients ≥3 years with compensated liver disease (1.1)
Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection (1.1)
Monotherapy: CHC in patients (≥18 years) with compensated liver disease previously untreated with interferon alpha. (1.1)
DOSAGE AND ADMINISTRATION
PegIntron is administered by subcutaneous injection
PegIntron Dose
(Adults)* PegIntron Dose (Pediatric Patients) REBETOL Dose*
(Adults) REBETOL Dose
(Pediatric Patients) *
Refer to Tables 1–7 of the full Prescribing Information.
PegIntron/ REBETOL Combination Therapy (2.1) 1.5 mcg/kg/week 60 mcg/m2/week 800–1400 mg orally daily with food 15 mg/kg/day orally with food in two divided doses
Dose reduction is recommended in patients experiencing certain adverse reactions or renal dysfunction. (2.3, 2.5)
DOSAGE FORMS AND STRENGTHS
Single-use vial (with 1.25 mL diluent) and REDIPEN® (3):
50 mcg per 0.5 mL, 80 mcg per 0.5 mL, 120 mcg per 0.5 mL, 150 mcg per 0.5 mL.
CONTRAINDICATIONS
Known hypersensitivity reactions, such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis to interferon alpha or any other product component. (4)
Autoimmune hepatitis (4)
Hepatic decompensation (Child-Pugh score >6 [class B and C]) in cirrhotic CHC patients before or during treatment (4)
Additional contraindications for combination therapy with ribavirin:
Pregnant women and men whose female partners are pregnant (4, 8.1)
Hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia) (4)
Creatinine clearance <50 mL/min (4)
WARNINGS AND PRECAUTIONS
Birth defects and fetal death with ribavirin: Patients must have a negative pregnancy test prior to therapy; use at least 2 forms of contraception and undergo monthly pregnancy tests (5.1)
Patients exhibiting the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
Hemolytic anemia with ribavirin (5.1)
Neuropsychiatric events (5.2)
History of significant or unstable cardiac disease (5.3)
Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication (5.4)
New or worsening ophthalmologic disorders (5.5)
Ischemic and hemorrhagic cerebrovascular events (5.6)
Severe decreases in neutrophil or platelet counts (5.7)
History of autoimmune disorders (5.8)
Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis (5.9, 5.10)
Pulmonary infiltrates or pulmonary function impairment (5.11)
Child-Pugh score >6 (class B and C) (4, 5.12)
Increased creatinine levels in patients with renal insufficiency (5.13)
Serious, acute hypersensitivity reactions and cutaneous eruptions (5.14)
Dental/periodontal disorders reported with combination therapy (5.16)
Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides >1000 mg/dL) (5.17)
Weight loss and growth inhibition reported with combination therapy in pediatric patients (5.18)
Peripheral neuropathy when used in combination with telbivudine (5.19)
ADVERSE REACTIONS
Most common adverse reactions (>40%) in adult patients receiving either PegIntron or PegIntron/REBETOL are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia and anxiety/emotional lability/irritability (6.1). Most common adverse reactions (>25%) in pediatric patients receiving PegIntron/REBETOL are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, vomiting (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Schering Corporation at 1-800-526-4099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Drug metabolized by CYP450: Caution with drugs metabolized by CYP2C8/9 (e.g., warfarin, phenytoin) or CYP2D6 (e.g., flecainide). (7.1)
Methadone: Monitor for increased narcotic effect. (7.2)
Nucleoside analogues: Closely monitor for toxicities. Discontinue nucleoside reverse transcriptase inhibitors or reduce dose or discontinue interferon, ribavirin, or both with worsening toxicities. (7.3)
Didanosine: Concurrent use with REBETOL is not recommended. (7.3)
USE IN SPECIFIC POPULATIONS
Ribavirin Pregnancy Registry: 1-800-593-2214 (8.1)
Pediatrics: safety and efficacy in pediatrics <3 years old have not been established (8.4)
Geriatrics: neuropsychiatric, cardiac, pulmonary, GI, and systemic (flu-like) adverse reactions may be more severe (8.5)
Organ transplant: safety and efficacy have not been studied (8.6)
HIV or HBV co-infection: safety and efficacy have not been established (8.7)
See 17 for PATIENT COUNSELING INFORMATION and the FDA-approved Medication Guide
Revised: 08/2009
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FULL PRESCRIBING INFORMATION: CONTENTS*
* Sections or subsections omitted from the full prescribing information are not listed
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
1 INDICATIONS AND USAGE
1.1 Chronic Hepatitis C
2 DOSAGE AND ADMINISTRATION
2.1 PegIntron/REBETOL Combination Therapy
2.2 PegIntron Monotherapy
2.3 Dose Reduction
2.4 Discontinuation of Dosing
2.5 Renal Function
2.6 Preparation and Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Use with Ribavirin
5.2 Neuropsychiatric Events
5.3 Cardiovascular Events
5.4 Endocrine Disorders
5.5 Ophthalmologic Disorders
5.6 Cerebrovascular Disorders
5.7 Bone Marrow Toxicity
5.8 Autoimmune Disorders
5.9 Pancreatitis
5.10 Colitis
5.11 Pulmonary Disorders
5.12 Hepatic Failure
5.13 Patients with Renal Insufficiency
5.14 Hypersensitivity
5.15 Laboratory Tests
5.16 Dental and Periodontal Disorders
5.17 Triglycerides
5.18 Impact on Growth-Pediatric Use
5.19 Peripheral Neuropathy
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Immunogenicity
6.3 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Drugs Metabolized by Cytochrome P-450
7.2 Methadone
7.3 Use with Ribavirin (Nucleoside Analogues)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Organ Transplant Recipients
8.7 HIV or HBV Co-infection
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Chronic Hepatitis C in Adults
14.2 Chronic Hepatitis C in Pediatrics
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Medication Guide
17.2 Pregnancy
17.3 HCV Transmission
17.4 Laboratory eva luations, Hydration, "Flu-like" Symptoms
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FULL PRESCRIBING INFORMATION
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
Alpha interferons, including PegIntron, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory eva luations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PegIntron therapy [see Warnings and Precautions (5) and Adverse Reactions (6.1)].
Use with Ribavirin
Ribavirin may cause birth defects and death of the unborn child. 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 REBETOL therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen. [See REBETOL package insert]
1 INDICATIONS AND USAGE
1.1 Chronic Hepatitis C
Combination therapy:
PegIntron® in combination with REBETOL® (ribavirin) is indicated for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PegIntron in combination with REBETOL:
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These indications are based on achieving undetectable HCV RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose.
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Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection [see Clinical Studies (14)].
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No safety and efficacy data are available for treatment of longer than one year.
Monotherapy (for patients who are intolerant to ribavirin):
PegIntron (peginterferon alfa-2b) is indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PegIntron alone:
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