HIGHLIGHTS OF PRESCRIBING INFORMATION
The highlights do not include all the information needed to u PegIntron safely and effectively. See full prescribing information for PegIntron.
PegIntron (Peginterferon alfa-2b) Injection, Powder for Solution for Subcutaneous U
Initial U.S. Approval: 2001
WARNING: RISK OF SERIOUS DISORDERS
AND RIBAVIRIN-ASSOCIATED EFFECTS
See full prescribing information for complete boxed warning.•May cau or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor cloly
and withdraw therapy with persistently vere or worning signs or symptoms of the above disorders. (5)
张伯成U with Ribavirin
•Ribavirin may cau 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, Do Reduction (2.3) [5/2009] Dosage and Administration, Discontinuation of Dosing (2.4) [3/2009] Warnings and Precautions, Endocrine Disorders (5.4) [1/2010] Warnings and Precautions, Ophthalmologic Disorders (5.5) [8/2009] Warnings and Precautions, Pulmonary Disorders (5.11) [8/2009] 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 dia. (1.1)
Patients with the following characteristics are less likely to benefit from re-treatment after failing a cour of therapy: previous nonrespon, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (1.1)
•Monotherapy: CHC in patients (≥18 years) with compensated liver dia previously untreated with interferon alpha. (1.1)
DOSAGE AND ADMINISTRATION
•PegIntron is administered by subcutaneous injection.
PegIntron Do (Adults)*PegIntron
Do
(Pediatric
Patients)
REBETOL
Do*
(Adults)
REBETOL
Do
(Pediatric
Patients)
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 2
divided dos
*Refer to Tables 1–7 of the full Prescribing Information.
•Do reduction is recommended in patients experiencing certain adver reactions or renal dysfunction. (2.3, 2.5)
DOSAGE FORMS AND STRENGTHS
Single-u 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 hypernsitivity 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 who female partners are pregnant. (4, 8.1)•Hemoglobinopathies (e.g., thalasmia 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, u at least 2 forms of contraception, and undergo monthly pregnancy tests. (5.1)
Patients exhibiting the following conditions should be cloly monitored and may require do reduction or discontinuation of therapy:
•Hemolytic anemia with ribavirin. (5.1)
•Neuropsychiatric events. (5.2)
•History of significant or unstable cardiac dia. (5.3)•Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication. (5.4)
•New or worning ophthalmologic disorders. (5.5)
•Ischemic and hemorrhagic cerebrovascular events. (5.6)
•Severe decreas 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)
•Incread creatinine levels in patients with renal insufficiency (5.13)•Serious, acute hypernsitivity 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 ud in combination with telbivudine (5.19)
ADVERSE REACTIONS
Most common adver reactions (>40%) in adult patients receiving either PegIntron or PegIntron/RE
BETOL are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, naua, myalgia and anxiety/ emotional lability/irritability (6.1). Most common adver 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
v/medwatch.
To report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or v/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 incread narcotic effect. (7.2)
•Nucleoside analogues: Cloly monitor for toxicities. Discontinue nucleoside rever transcripta inhibitors or reduce do or discontinue interferon, ribavirin, or both with worning toxicities. (7.3)•Didanosine: Concurrent u 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) adver reactions may be more vere (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
Revid: 01/2010
FULL PRESCRIBING INFORMATION: CONTENTS *
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
1 INDICATIONS AND USAGE
1.1 Chronic Hepatitis C
英语封面
2 DOSAGE AND ADMINISTRATION
2. 1 PegIntron/REBETOL Combination Therapy
2.2 PegIntron Monotherapy
2.3 Do 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 U 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 Hypernsitivity
5.15 Laboratory Tests
5.16 Dental and Periodontal Disorders
5.17 Triglycerides
5.18 Impact on Growth-Pediatric U
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 U with Ribavirin (Nucleoside Analogues)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric U
8.5 Geriatric U
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 Evaluations, Hydration, "Flu-like" Symptoms
* Sections or subctions omitted from the full prescribing information are not listed
FULL PRESCRIBING INFORMATION
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
Alpha interferons, including PegIntron, may cau or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored cloly with periodic clinical and laboratory evaluations. Patients with persistently vere or worning signs or symptoms of the conditions should be withdrawn from therapy.
In many, but not all cas, the disorders resolve after stopping PegIntron therapy [e Warnings and Precautions (5) and Adver Reactions (6.1)].
U with Ribavirin
Ribavirin may cau 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 caus hemolytic anemia. The anemia associated with REBETOL therapy may result in a worning of cardiac dia. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinog
en. [See REBETOL package inrt]
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 dia.
The following points should be considered when initiating therapy with PegIntron in combination with REBETOL:
五禽戏是哪五禽
•The indications are bad on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Respon (SVR) 24 weeks after the last do.
•Patients with the following characteristics are less likely to benefit from retreatment after failing a cour of therapy: previous nonrespon, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection [e Clinical Studies (14)].
•No safety and efficacy data are available for treatment of longer than 1 year.
Monotherapy (for patients who are intolerant to ribavirin):
PegIntron (peginterferon alfa-2b) is indicated for u alone for the treatment of chronic hepatitis C in patients with compensated liver dia previously untreated with interferon alpha and who are at least 18 years of age.
The following point should be considered when initiating therapy with PegIntron alone:
•Combination therapy with REBETOL is preferred over PegIntron monotherapy unless there are contraindications to or significant intolerance of REBETOL.
Combination therapy provides substantially better respon rates than monotherapy [e Clinical St
udies (14)].
2 DOSAGE AND ADMINISTRATION
2. 1 PegIntron/REBETOL Combination Therapy
REBETOL should be taken with food. REBETOL should not be ud in patients with creatinine clearance <50 mL/min.
Adults
The recommended do of PegIntron is 1.5 mcg/kg/week subcutaneously in combination with 800 to 1400 mg of REBETOL orally bad on patient body weight. The volume of PegIntron to be injected depends on the strength of PegIntron and patient's body weight (e Table 1).
Duration of Treatment – Interferon Alpha-naïve Patients
The treatment duration for patients with genotype 1 is 48 weeks. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of HCV-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy. Patients with genotype 2 and 3 should be treated for 24 weeks.
Duration of Treatment – Re-treatment with PegIntron/REBETOL of Prior Treatment Failures
麻刀The treatment duration for patients who previously failed therapy is 48 weeks, regardless of HCV genotype. Re-treated patients who fail to achieve undetectable HCV-RNA at Week 12 of therapy, or who HCV-RNA remains detectable after 24 weeks of therapy, are highly unlikely to achieve SVR and discontinuation of therapy should be considered [e Clinical Studies (14.1)].
TABLE 1 Recommended PegIntron Combination Therapy Dosing (Adults)
Body weight
kg (lbs)
PegIntron
REDIPEN® or Vial
Strength to U
Amount of
PegIntron (mcg)
to Administer
Volume (mL)*
of PegIntron进系统黑屏
to Administer
REBETOL
Daily Do
REBETOL Number
of Capsules
<40
(<88)
50 mcg per 0.5 mL 50 0.5 800 mg/day
2 × 200 mg capsules A.M.
2 × 200 mg capsules P.M.
40 – 50
(88 – 111)
64 0.4 800 mg/day
有关历史的成语
2 × 200 mg capsules A.M.
2 × 200 mg capsules P.M.
51 – 60
(112 – 133)
80 mcg per 0.5 mL
80 0.5 800 mg/day
2 × 200 mg capsules A.M.
2 × 200 mg capsules P.M.
61 – 65
(134 – 144)
96 0.4 800 mg/day
2 × 200 mg capsules A.M.
2 × 200 mg capsules P.M.
66 – 75
(145 – 166)山茶花几月开花
96 0.4 1000 mg/day
2 × 200 mg capsules A.M.
3 × 200 mg capsules P.M.
76 – 80
120 mcg per 0.5 mL
120 0.5 1000 mg/day 2 × 200 mg capsules A.M.
(167 – 177) 3 × 200 mg capsules P.M.
81 – 85
(178 – 187)
1200 mg/day
3 × 200 mg capsules A.M.
3 × 200 mg capsules P.M.
86 – 105
(188 – 231)
150 mcg per 0.5 mL 150 0.5 1200 mg/day
3 × 200 mg capsules A.M.
3 × 200 mg capsules P.M.
>105
(>231)
†††1400 mg/day 3 × 200 mg capsules A.M.
4 × 200 mg capsules P.M.
†For patients weighing >105 kg (>231 pounds), the PegIntron do of 1.5 mcg/kg/week should be calculated bad on the individual patient weight. Two vials of PegIntron may be necessary to provide the do.
Pediatric Patients
Dosing for pediatric patients is determined by body surface area for PegIntron and by body weight for REBETOL. The recommended do of PegIntron is 60mcg/m2/week subcutaneously in combination with 15 mg/kg/day of REBETOL orally in 2 divided dos (e Table 2) for pediatric patients ages 3 to 17 years. Patients who reach their 18th birthday while receiving PegIntron/REBETOL, should remain on the pediatric dosing regimen. The treatment duration for patients with genotype 1 is 48 weeks. Patients with genotype 2 and 3 should be treated for 24 weeks.
TABLE 2 Recommended REBETOL* Dosing in Combination Therapy (Pediatrics)
Body weight
kg (lbs)
REBETOL Daily Do REBETOL Number of Capsules
<47
(<103)
15 mg/kg/day U REBETOL Oral Solution†
47 – 59
(103–131)
800 mg/day
2 × 200 mg capsules A.M.
2 × 200 mg capsules P.M.
60 – 73
(132–162)
1000 mg/day
2 × 200 mg capsules A.M.
3 × 200 mg capsules P.M.
>73
(>162)
1200 mg/day
3 × 200 mg capsules A.M.
3 × 200 mg capsules P.M.
*REBETOL to be ud in combination with PegIntron 60 mcg/m2 weekly.
†REBETOL Oral Solution may be ud for any patient regardless of body weight.
2.2 PegIntron Monotherapy
The recommended do of PegIntron regimen is 1 mcg/kg/week subcutaneously for 1 year administered on the same day of the week. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of HCV-RNA at 12 weeks of therapy, or who HCV-RNA levels remain detectable after 24 weeks of therapy. The volume of PegIntron to be injected depends on patient weight (e Table 3).
TABLE 3 Recommended PegIntron Monotherapy Dosing
Body weight
kg (lbs)
PegIntron REDIPEN or
Vial Strength to U
Amount of PegIntron
(mcg) to Administer
Volume (mL)* of
PegIntron to Administer ≤45
(≤100)
40 0.4
46 – 56
(101 – 124)
50 mcg per 0.5 mL
50 0.5
57 – 72
(125 – 159)
64 0.4
73 – 88
80 mcg per 0.5 mL
80 0.5
(160 – 195) 89 – 106(196 – 234) 96
0.4 107 – 136(235 – 300) 120 mcg per 0.5 mL
120
0.5 137 – 160(301 – 353)
150 mcg per 0.5 mL
150
0.5
2.3 Do Reduction
If a rious adver reaction develops during the cour of treatment [e Warnings and Precaution
s (5)] discontinue or modify the dosage of PegIntron and REBETOL until the adver event abates or decreas in verity. If persistent or recurrent rious adver events develop despite adequate dosage adjustment, discontinue treatment. For guidelines for do modifications and discontinuation bad on depression or laboratory parameters, e Tables 4 and 5. Do reduction of PegIntron in adult patients on PegIntron/
REBETOL combination therapy is accomplished in a two-step process from the original starting do of 1.5 mcg/kg/week, to 1 mcg/kg/week, then to 0.5 mcg/kg/week, if needed. Do reduction in patients on PegIntron monotherapy is accomplished by reducing the original starting do of 1 mcg/kg/week to 0.5 mcg/kg/week. Do reduction of PegIntron in adults may be accomplished by utilizing a lower do strength or administering a lesr volume as shown in Table 6 or 7.
In the adult combination therapy Study 2, do reductions occurred in 42% of subjects receiving PegIntron 1.5 mcg/kg plus
REBETOL 800 mg daily, including 57% of tho subjects weighing 60 kg or less. In Study 4, 16% of subjects had a do reduction of PegIntron to 1 mcg/kg in combination with REBETOL, with an additional 4% requiring the cond do reduction of PegIntron to 0.5mcg/kg due to adver events [e Adver Reactions (6.1)].
Do reduction in pediatric patients is accomplished by modifying the recommended do in a 2-step process from the original starting do of 60 mcg/m 2/week, to 40 mcg/m 2/week, then to 20 mcg/m 2/week, if needed (e Tables 4 and 5). In the pediatric combination therapy trial, do reductions occurred in 25% of subjects receiving PegIntron 60 mcg/m 2 weekly plus REBETOL 15 mg/kg daily.TABLE 4 Guidelines for Modification or Discontinuation of PegIntron or PegIntron/REBETOL and for Scheduling Visits for Patients
with Depression Initial Management (4–8 weeks) Depression Status
Depression Severity * Do Modification Visit Schedule Remains Stable Improves Worns Mild No change
Evaluate once weekly by visit or phone.
Continue weekly visit schedule.
Resume normal visit schedule. See moderate or vere depression Moderate
Adults: Adjust Do †
Pediatrics: Decrea do to 40 mcg/m 2/week, then to 20mcg/m 2/week, if 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 do.
See vere depression Severe
Discontinue PegIntron/REBETOL permanently.
如何在网上写小说Obtain immediate psychiatric consultation.
Psychiatric therapy as necessary
†For patients on PegIntron/REBETOL combination therapy: 1st do reduction of PegIntron is to 1 mcg/kg/week, 2nd do reduction (if needed) of PegIntron is to 0.5 mcg/kg/week. For patients on PegIntron monotherapy: decrea PegIntron do to 0.5 mcg/kg/week.
