A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Roferon-A Warnings, Precautions, Pregnancy, Nursing, Abuse - Peginterferon alfa-2b
Roferon-A Warnings, Precautions, Pregnancy, Nursing, Abuse - Peginterferon alfa-2b
WARNINGS
WARNING
Alpha interferons, including PEG-Intron, 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conditions should be withdrawn from therapy.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 many but not all cases these
disorders resolve after stopping PEG-Intron therapy. See WARNINGS , ADVERSE
REACTIONS. |
Patients should be monitored for the following serious conditions, some of
which may become life threatening. Patients with persistently severe or worsening
signs or symptoms should be withdrawn from therapy.
Neuropsychiatric events
Life-threatening or fatal neuropsychiatric events, including suicide, suicidal
and homicidal ideation, depression, relapse of drug addiction/overdose, and
aggressive behavior have occurred in patients with and without a previous psychiatric
disorder during PEG-Intron treatment and follow-up. Psychoses and hallucinations
have been observed in patients treated with alpha interferons. PEG-Intron should
be used with extreme caution in patients with a history of psychiatric disorders.
Patients should be advised to report immediately any symptoms of depression
and/or suicidal ideation to their prescribing physicians. Physicians should
monitor all patients for evidence of depression and other psychiatric symptoms.
In severe cases, PEG-Intron should be stopped immediately and psychiatric intervention
instituted.
Bone marrow toxicity
PEG-Intron suppresses bone marrow function, sometimes resulting in severe cytopenias.
PEG-Intron should be discontinued in patients who develop severe decreases in
neutrophil or platelet counts. Very rarely alpha interferons may be associated
with aplastic anemia. (See DOSAGE AND ADMINISTRATION)
Endocrine disorders
PEG-Intron causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia
has been observed in patients treated with PEG-Intron. Diabetes mellitus has
been observed in patients treated with alpha interferons. Patients with these
conditions who cannot be effectively treated by medication should not begin
PEG-Intron therapy. Patients who develop these conditions during treatment and
cannot be controlled with medication should not continue PEG-Intron therapy.
Cardiovascular events
Cardiovascular events, which include hypotension, arrhythmia, tachycardia,
cardiomyopathy, and myocardial infarction have been observed in patients treated
with PEG-Intron. PEG-Intron should be used cautiously in patients with cardiovascular
disease. Patients with a history of myocardial infarction and arrhythmic disorder
who require PEG-Intron therapy should be closely monitored (see Laboratory
tests ).
Colitis
Fatal and nonfatal ulcerative and hemorrhagic colitis has been observed within
12 weeks of the start of alpha interferon treatment. Abdominal pain, bloody
diarrhea, and fever are the typical manifestations. PEG-Intron treatment should
be discontinued immediately in patients who develop these symptoms and signs.
The colitis usually resolves within 1-3 weeks of discontinuation of alpha interferons.
Pancreatitis
Fatal and nonfatal pancreatitis has been observed in patients treated with
alpha interferon. PEG-Intron therapy should be suspended in patients with signs
and symptoms suggestive of pancreatitis and discontinued in patients diagnosed
with pancreatitis.
Autoimmune disorders
Development or exacerbation of autoimmune disorders (e.g., thyroiditis, thrombocytopenia,
rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus,
psoriasis) have been observed in patients receiving PEG-Intron. PEG-Intron should
be used with caution in patients with autoimmune disorders.
Pulmonary disorders
Dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in
patient deaths, have been associated with PEG-Intron or alpha interferon therapy.
Patients with pulmonary infiltrates or pulmonary function impairment should
be closely monitored.
Hypersensitivity
Serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction,
anaphylaxis) have been rarely observed during alpha interferon therapy. If such
a reaction develops during treatment with PEG-Intron, discontinue treatment
and institute appropriate medical therapy immediately. Transient rashes do not
necessitate interruption of treatment.
PRECAUTIONS
- PEG-Intron has not been studied in patients who have failed other alpha
interferon treatments.
- The safety and efficacy of PEG-Intron for the treatment of hepatitis C in
patients who have received liver or other organ transplant recipients have
not been studied.
- The safety and efficacy of PEG-Intron for the treatment of patients with
HCV coinfected with HIV or HBV have not been established.
Ophthalmologic disorders: Retinal hemorrhages, cotton wool
spots, and retinal artery or vein obstruction have been observed after treatment
with PEG-Intron or alpha interferons. Patients who have diabetes mellitus or
hypertension should have eye examinations before the start of PEG-Intron treatment.
Patients with renal failure: Patients with impairment of
renal function should be closely monitored for signs and symptoms of interferon
toxicity and doses of PEG-Intron should be adjusted accordingly. PEG-Intron
should be used with caution in patients with creatinine clearance <50 mL/min.
See DOSAGE AND ADMINISTRATION.
Immunogenicity: One percent of patients (7/734) receiving
PEG-Intron developed low-titer ( ≤64) neutralizing antibodies to INTRON
A. The clinical and pathological significance of the appearance of serum neutralizing
antibodies is unknown. No apparent correlation of antibody development to clinical
response or adverse events was observed. The incidence of post-treatment binding
antibody was approximately 10% for patients receiving PEG-Intron and approximately
15% for patients receiving INTRON A. The data reflect the percentage of patients
whose test results were considered positive for antibodies to PEG-Intron in
a Biacore assay that is used to measure binding antibodies, and in an antiviral
neutralization assay which measures serum neutralizing antibodies. The percentage
of patients whose test results were considered positive for antibodies is highly
dependent on the sensitivity and specificity of the assays. Additionally the
observed incidence of antibody positivity in these assays may be influenced
by several factors including sample timing and handling, concomitant medications,
and underlying disease. For these reasons, comparison of the incidence of antibodies
to PEG-Intron with the incidence of antibodies to other products may be misleading.
Laboratory Tests: PEG-Intron may cause severe decreases
in neutrophil and platelet counts, and abnormality of TSH. In 10% of patients
treated with PEG-Intron ALT levels rose 2 to 5-fold above baseline. The elevations
were transient and were not associated with deterioration of other liver functions.
Patients on PEG-Intron therapy should have hematology and blood chemistry testing
before the start of treatment and then periodically thereafter. In the clinical
trial CBC (including neutrophil and platelet counts) and chemistries (including
AST, ALT, and bilirubin) were measured during the treatment period at weeks
2, 4, 8, 12, and then at 6-week intervals or more frequently if abnormalities
developed. TSH levels were measured every 12 weeks during the treatment period.
Patients who have pre-existing cardiac abnormalities should have electrocardiograms
administered before treatment with PEG-Intron.
Information for Patients: Patients receiving PEG-Intron
should be directed in its appropriate use, informed of the benefits and risks
associated with treatment, and referred to the MEDICATION GUIDE .
A puncture-resistant container for the disposal of used syringes and needles
should be supplied to the patient for at home use. Patients should be thoroughly
instructed in the importance of proper disposal and cautioned against any reuse
of needles and syringes. The full container should be disposed of according
to the directions provided by the physician (see MEDICATION GUIDE ).
Patients should be informed that there are no data evaluating whether PEG-Intron
therapy will prevent transmission of HCV infection to others. Also, it is not
known if treatment with PEG-Intron will cure hepatitis C or prevent cirrhosis,
liver failure, or liver cancer that may be the result of infection with the
hepatitis C virus.
Patients should be advised that laboratory evaluations are required before
starting therapy and periodically thereafter (see Laboratory Tests ).
It is advised that patients be well-hydrated, especially during the initial
stages of treatment. "Flu-like" symptoms associated with administration of PEG-Intron
may be minimized by bedtime administration of PEG-Intron or by use of antipyretics.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: PEG-Intron has not been tested for its carcinogenic
potential.
Mutagenesis: Neither PEG-Intron, nor its components interferon
or methoxypolyethylene glycol caused damage to DNA when tested in the standard
battery of mutagenesis assays, in the presence and absence of metabolic activation.
Impairment of Fertility: Irregular menstrual cycles were
observed in female cynomolgus monkeys given subcutaneous injections of 4239
µg/m 2 PEG-Intron every other day for one month, at approximately
345 times the recommended weekly human dose (based upon body surface area).
These effects included transiently decreased serum levels of estradiol and progesterone,
suggestive of anovulation. Normal menstrual cycles and serum hormone levels
resumed in these animals 2 to 3 months following cessation of PEG-Intron treatment.
Every other day dosing with 262 µg/m 2 (approximately 21 times the
weekly human dose) had no effects on cycle duration or reproductive hormone
status. The effects of PEG-Intron on male fertility have not been studied.
Pregnancy Category C: Non-pegylated Interferon alfa-2b,
has been shown to have abortifacient effects in Macaca mulatta (rhesus
monkeys) at 15 and 30 million IU/kg (estimated human equivalent of 5 and 10
million IU/kg, based on body surface area adjustment for a 60 kg adult). PEG-Intron
should be assumed to also have abortifacient potential. There are no adequate
and well-controlled studies in pregnant women. PEG-Intron therapy is to be used
during pregnancy only if the potential benefit justifies the potential risk
to the fetus. Therefore, PEG-Intron is recommended for use in fertile women
only when they are using effective contraception during the treatment period.
Nursing Mothers: It is not known whether the components
of PEG-Intron are excreted in human milk. Because of the potential for adverse
reactions from the drug in nursing infants, a decision must be made whether
to discontinue nursing or discontinue the treatment, taking into account the
importance of the product to the mother.
Pediatric Use Safety and effectiveness in pediatric patients
below the age of 18 years have not been established.
Geriatric Patients Clinical studies of PEG-Intron did not
include sufficient numbers of subjects aged 65 and over to determine whether
they respond differently than younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. However, treatment with alpha interferons, including PEG-Intron, is
associated with CNS, cardiac, and systemic (flu-like) adverse effects. Because
these adverse reactions may be more severe in the elderly, caution should be
exercised in use of PEG-Intron in this population. This drug is known to be
substantially excreted by the kidney. Because elderly patients are more likely
to have decreased renal function, the risk of toxic reactions to this drug may
be greater in patients with impaired renal function.
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