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
Tegretol Warnings, Precautions, Pregnancy, Nursing, Abuse - Carbamazepine
Tegretol Warnings, Precautions, Pregnancy, Nursing, Abuse - Carbamazepine
WARNINGS
Patients with a history
of adverse hematologic reaction
to any drug may be particularly at risk.
Severe dermatologic reactions including toxic
epidermal necrolysis
(Lyell's syndrome) and Stevens-Johnson syndrome,
have been reported with carbamazepine. These reactions have been
extremely rare. However, a few fatalities have been reported.
Carbamazepine has shown mild anticholinergic
activity: therefore, patients with increased intraocular
pressure should be
closely observed during therapy.
Because of the relationship of the drug
to other tricyclic compounds, the possibility of activation
of a latent psychosis
and in elderly patients,
of confusion or agitation
should be borne in mind.
PRECAUTIONS
General
Before initiating therapy,
a detailed history and
physical examination
should be made.
Carbamazepine should be used with caution in patients with a mixed
seizure disorder that includes atypical
absence seizures, since
in these patients carbamazepine has been associated with increased
frequency of generalized
convulsions (see INDICATIONS AND
USAGE).
Therapy should be prescribed only after critical
benefit-to-risk appraisal in patients with a history
of cardiac, hepatic
or renal damage, adverse
hematologic reaction
to other drugs, or interrupted courses of therapy with carbamazepine.
Since a given dose of
carbamazepine
suspension will
produce higher peak levels than the same dose
given as the tablet,
it is recommended that patients given the suspension
be started on lower doses and increased slowly to avoid unwanted
side effects (see DOSAGE
AND ADMINISTRATION).
Information for the Patient
Patients should be made aware of the early toxic
signs and symptoms of a potential
hematologic problem, such
as fever, sore
throat, rash,
ulcers in the mouth, easy
bruising, petechial
or purpuric hemorrhage,
and should be advised to report
to the physician immediately
if any such signs or symptoms
appear.
Since dizziness and
drowsiness may occur,
patients should be cautioned about the hazards of operating machinery
or automobiles or engaging in other potentially dangerous tasks.
Laboratory Tests
Complete pretreatment
blood counts, including
platelets and possibly reticulocytes and serum
iron, should be obtained
as a baseline. If a patient in the course of treatment
exhibits low or decreased white
blood cell
or platelet counts, the patient
should be monitored closely. Discontinuation of the drug
should be considered if any evidence
of significant bone
marrow depression develops.
Baseline and periodic
evaluations of liver function,
particularly in patients with a history
of liver disease,
must be performed during treatment with this drug
since liver damage may
occur. The drug should
be discontinued immediately in cases of aggravated liver
dysfunction or active
liver disease.
Baseline and periodic
eye examinations, including
slit-lamp, funduscopy and tonometry, are recommended since many
phenothiazines
and related drugs have been shown to cause
eye changes.
Baseline and periodic
complete urinalysis
and BUN determinations are
recommended for patients treated with this agent
because of observed renal dysfunction.
Monitoring of blood levels
(see CLINICAL PHARMACOLOGY)
has increased the efficacy
and safety of anticonvulsants. This monitoring may be particularly
useful in cases of dramatic increase in seizure
frequency and for verification of compliance. In
addition, measurement of drug
serum levels may aid in
determining the cause
of toxicity when more
than one medication is being used.
Thyroid function tests
have been reported to show
decreased values with carbamazepine administered alone.
Hyponatremia has been reported in association
with carbamazepine
use, either alone or in combination with other drugs.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Carbamazepine, when administered to Sprague-Dawley rats for two
years in the diet at doses
of 25, 75, and 250 mg/kg/day, resulted in a dose-related increase
in the incidence of
hepatocellular
tumors in females and of benign interstitial cell
adenomas in the testes
of males.
Carbamazepine must, therefore, be considered to be carcinogenic
in Sprague-Dawley rats. Bacterial and mammalian mutagenicity studies
using carbamazepine produced negative
results. The significance of these findings relative to the use
of carbamazepine
in humans is at present, unknown.
Pregnancy Category C
Carbamazepine has been shown to have adverse effects in reproduction
studies in rats when given orally in dosages 10-25 times the maximum
human daily dosage of
1200 mg. In rat
teratology studies,
2 of 135 offspring showed kinked ribs at 250 mg/kg and 4 of 119
offspring at 650 mg/kg showed other anomalies (cleft palate, 1;talipes,
1;anophthalmos, 2). In reproduction
studies in rats, nursing
offspring demonstrated a lack of weight
gain and an unkempt appearance
at a maternal dosage
level of 200 mg/kg.
There are no adequate and
well-controlled studies in pregnant
women. Epidemiological data suggest that there may be an association
between the use of carbamazepine
during pregnancy and
congenital malformations,
including spina bifida. Carbamazepine should be used during pregnancy
only if the potential benefit
justifies the potential
risk to the fetus.
Retrospective case reviews
suggest that, compared with monotherapy, there may be a higher prevalence
of teratogenic effects
associated with the use of anticonvulsants in combination therapy.
Therefore, monotherapy is recommended for pregnant
women.
It is important to note
that anticonvulsant
drugs should not be discontinued in patients in whom the drug
is administered to prevent major seizures because of the strong
possibility of precipitating status
epilepticus with attendant hypoxia
and threat to life. In individual
cases where the severity and frequency
of the seizure disorder
are such that removal of
medication does not pose a serious threat to the patient,
discontinuation of the drug may be considered prior to and during
pregnancy, although
it cannot be said with any confidence that even minor
seizures do not pose some hazard to the developing embryo
or fetus.
Labor and Delivery
The effect of carbamazepine
on human labor
and delivery is unknown.
Nursing Mothers
During lactation,
concentration
of carbamazepine
in milk is approximately
60% of the maternal
plasma concentration.
Because of the potential
of serious adverse reactions in nursing
infants from carbamazepine, a decision should be made whether to
discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness
in children below the age
of 6 years have not been established.
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