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
Infergen Warnings, Precautions, Pregnancy, Nursing, Abuse - Interferon alfacon-1
Infergen Warnings, Precautions, Pregnancy, Nursing, Abuse - Interferon alfacon-1
WARNINGS
Treatment with Infergen should be administered under the guidance
of a qualified physician,
and may lead to moderate-to-severe
adverse experiences requiring dose
reduction, temporary dose
cessation, or discontinuation of further therapy.
Withdrawal from study for adverse events occurred in 7% of patients
treated with 9 mcg Infergen
(including 4% due to psychiatric
events).
SEVERE PSYCHIATRIC ADVERSE EVENTS MAY MANIFEST IN PATIENTS RECEIVING
THERAPY WITH INTERFERON, INCLUDING INFERGEN. DEPRESSION, SUICIDAL
IDEATION, AND SUICIDE ATTEMPT MAY OCCUR. The incidence
of psychiatric events
of suicidal ideation was small (1%) for patients treated with 9
mcg Infergen compared to
the overall incidence
(55%) of psychiatric
events. Infergen should be used with caution in patients who report
a history of depression
and physicians should monitor
all patients for evidence
of depression. Physicians should inform patients of the possible
development of depression
prior to initiation of Infergen therapy,
and patients should report
any sign or symptom
of depression immediately. Other prominent psychiatric
adverse events may also occur, including nervousness, anxiety,
emotional lability, abnormal thinking, agitation,
or apathy (see PRECAUTIONS
).
INFERGEN SHOULD BE ADMINISTERED WITH CAUTION TO
PATIENTS WITH PRE-EXISTING CARDIAC DISEASE. Hypertension and supraventricular
arrhythmias, chest pain
and myocardial infarction
have been associated with interferon
therapies.6
No studies with Infergen have been conducted in patients with decompensated
hepatic disease. Patients with decompensated hepatic
disease should not be
treated with Infergen, and patients who develop symptoms of hepatic
decompensation, such as
jaundice, ascites,
coagulopathy, or decreased serum albumin, should halt further interferon
therapy.
PRECAUTIONS
General
Since the use of type-I interferons has been associated with depression,
Infergen therapy should
not be used in patients with a history
of severe psychiatric disorders and should be discontinued in patients
developing severe depression,
suicidal ideation,
or other severe psychiatric
disorders (see WARNINGS
).
Infergen should be used with caution in patients with a history
of cardiac disease. Hypertension (5%), tachycardia
(4%), and palpitation
(3%) were the most common cardiovascular
adverse events reported for 9 mcg
Infergen therapy, with 1% of patients reporting tachyarrhythmias
which were dose-limiting (see WARNINGS
).
Infergen should be used cautiously in patients with abnormally
low peripheral blood cell
counts or who are receiving agents that are known to cause
myelosuppression. Leukopenia, particularly granulocytopenia, may
be severe in patients treated with alpha
interferons, including Infergen, and may necessitate dose
reduction or temporary dose
cessation. Thrombocytopenia is a common, but less severe, event
often associated with alpha
interferon therapy.
Therapy should be withheld if the absolute
neutrophil count
(ANC) is < 500 x 106/L or if the platelet
count is < 50 x 109/L.
Transplantation patients, or other chronically immunosuppressed
patients, should receive Infergen therapy
with caution.
Serious acute hypersensitivity
reactions have been reported in rare instances following treatment
with alpha interferons.
If hypersensitivity reactions occur (eg, urticaria,
angioedema, bronchoconstriction,
anaphylaxis), the drug
should be discontinued immediately and appropriate
medical treatment instituted.
Infergen should be administered with caution to patients with a
history of endocrine
disorders. Abnormal thyroid
stimulating hormone
(TSH) and free thyroxine
(T4) level with hypothyroidism
occurred in 4% of patients administered 9 mcg
Infergen, and thyroid
supplements were required in approximately two t.i.d.
of those patients.
Ophthalmologic disorders have been reported with treatment
with alpha interferons. Investigators using alpha
interferons have reported the occurrence of retinal
hemorrhages, cotton wool
s.o.s. and retinal
artery or vein
obstruction in rare instances. Any patient
complaining of loss of
visual acuity
or visual field should
have an eye examination.
Because these ocular
events may occur in conjunction with other disease
states, a visual exam
prior to initiation of interferon
therapy is recommended
in patients with diabetes mellitus or hypertension.
Exacerbation of autoimmune disease
has been reported in patients receiving type-I interferon
therapy. Infergen should not be used in patients with autoimmune
hepatitis and be used
with caution in patients with other autoimmune disorders.
While fever may be related
to the flu-like symptoms reported in patients treated with Infergen,
when fever occurs, other
possible causes of persistent fever should be ruled out.
Information for Patients
If home use is determined to be desirable by the physician,
instructions on appropriate
use should be given by a health
care professional. The patient must be instructed as to the proper
dosage and administration.
Information included in the full "Information for Patients"
leaflet (provided separately) should be fully reviewed with the
patient; it is not a disclosure of all, or possible, adverse effects.
The most common adverse reactions occurring with Infergen therapy
are flu-like symptoms including fatigue, fever, rigors, headache,
arthralgia, myalgia,
and increased sweating. Non-narcotic analgesics and bedtime administration
of Infergen may be used to prevent or lessen some of these symptoms.
Additionally, patients must be thoroughly instructed in the importance
of proper disposal procedures and cautioned against the reuse of
needles, syringes, or re-entry
of the drug product. A
puncture-resistant container
for the disposal of used syringes and needles should be used by
the patient and should
be disposed of according to the directions provided by the health
care provider.
Laboratory Tests
Laboratory tests are recommended for all patients on Infergen therapy,
prior to beginning treatment
(baseline), 2 weeks after initiation of therapy, and periodically
thereafter during the 24 weeks of therapy
at the discretion of the physician. Following completion of Infergen
therapy, any abnormal
test values should be monitored periodically. The entrance criteria
that were used for the clinical
study of Infergen may be considered as a guideline to acceptable
baseline values for
initiation of treatment:
- Platelet count 75 x 109/L
- Hemoglobin concentration 100 g/L
- ANC 1500 x 106/L
- Serum creatinine
concentration
< 180 µmol/L (< 2.0 mg/dL) or creatinine
clearance > 0.83
mL/second (> 50 mL/minute)
- Serum albumin concentration 25
g/L
- Bilirubin within normal
limits
- TSH and T4 within normal
limits
Neutropenia, thrombocytopenia,
hypertriglyceridemia,
and thyroid disorders
have been reported with administration
of Infergen (see ADVERSE REACTIONS).
Therefore, these laboratory
parameters should be monitored closely.
Drug Interactions
No formal drug interaction
studies have been conducted with Infergen. Infergen should be used
cautiously in patients who are receiving agents that are known to
cause myelosuppression
or with agents known to be metabolized via the cytochrome
P-450 pathway.7 Patients taking drugs that are metabolized
by this pathway should
be monitored closely for changes in the therapeutic
and/or toxic levels of
concomitant drugs.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: No
carcinogenicity data for Infergen are available in animals or humans.
Mutagenesis: Infergen was not mutagenic when
tested in several in vitro assays, including the Ames bacterial
mutagenicity assay and an in vitro cytogenetic assay
in human lymphocytes,
either in the presence or absence
of metabolic activation.
Impairment of Fertility: Infergen at doses as high
as 100 mcg/kg did not selectively affect
reproductive performance
or the development of the offspring when administered SC to male
and female golden Syrian
hamsters for 70 and 14 days before mating, respectively, and then
through mating and to day 7 of pregnancy.
Pregnancy Category C
Infergen has been shown to have embryolethal or abortifacient
effects in golden Syrian hamsters when given at 135 times the human
dose and in cynomolgus
and rhesus monkeys when given at 9 to 81 times (based on body surface
area) the human dose.
There are no adequate and
well-controlled studies in pregnant
women. Infergen should not be used during pregnancy. If a woman
becomes pregnant or
plans to become pregnant
while taking Infergen, she should be informed of the potential
hazards to the fetus. Males and females treated with Infergen should
be advised to use effective contraception.
Nursing Mothers
It is not known whether Infergen is excreted in human
milk. Because many drugs are excreted in human
milk, caution should be exercised if Infergen is administered to
a nursing woman. The
effect on the nursing
neonate of orally ingested
Infergen in breast milk
has not been evaluated.
Pediatric Use
The safety and effectiveness
of Infergen have not been established in patients below the age
of 18 years. Infergen therapy
is not recommended in pediatric
patients.
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