OVERDOSAGE
Acute Toxicity
Lowest known lethal dose: adults, >60 g (39-year-old man).
Highest known doses survived: adults, 30 g (31-year-old woman); children, 10 g
(6-year-old boy); small children, 5 g (3-year-old girl).
Oral LD50 in animals (mg/kg): mice, 1100-3750; rats,
3850-4025; rabbits, 1500-2680; guinea pigs, 920.
Signs and Symptoms
The first signs and symptoms appear after 1-3 hours.
Neuromuscular disturbances are the most prominent. Cardiovascular disorders are
generally milder, and severe cardiac complications occur only when very high
doses (>60 g) have been ingested.
Respiration: Irregular breathing, respiratory
depression.
Cardiovascular System: Tachycardia, hypotension or
hypertension, shock, conduction disorders.
Nervous System and Muscles: Impairment of
consciousness ranging in severity to deep coma. Convulsions, especially in
small children. Motor restlessness, muscular twitching, tremor, athetoid
movements, opisthotonos, ataxia, drowsiness, dizziness, mydriasis, nystagmus,
adiadochokinesia, ballism, psychomotor disturbances, dysmetria. Initial
hyperreflexia, followed by hyporeflexia.
Gastrointestinal Tract: Nausea, vomiting.
Kidneys and Bladder: Anuria or oliguria, urinary
retention
Laboratory Findings: Isolated instances of overdosage
have included leukocytosis, reduced leukocyte count, glycosuria, and acetonuria.
ECG may show dysrhythmias.
Combined Poisoning: When alcohol, tricyclic
antidepressants, barbiturates, or hydantoins are taken at the same time, the
signs and symptoms of acute poisoning with carbamazepine may be aggravated or
modified.
Treatment
For the most up to date information on management of
carbamazepine overdose, please contact the poison center for your area by
calling 1-800-222-1222. The prognosis in cases of carbamazepine poisoning is
generally favorable. Of 5,645 cases of carbamazepine exposures reported to US
poison centers in 2002, a total of 8 deaths (0.14% mortality rate) occurred.
Over 39% of the cases reported to these poison centers were managed safely at
home with conservative care. Successful management of large or intentional
carbamazepine exposures requires implementation of supportive care, frequent
monitoring of serum drug concentrations, as well as aggressive but appropriate
gastric decontamination.
Elimination of the Drug: The primary method for
gastric decontamination of carbamazepine overdose is use of activated charcoal.
For substantial recent ingestions, gastric lavage may also be considered.
Administration of activated charcoal prior to hospital assessment has the
potential to significantly reduce drug absorption. There is no specific
antidote. In overdose, absorption of carbamazepine may be prolonged and delayed.
More than one dose of activated charcoal may be beneficial in patients that have
evidence of continued absorption (e.g., rising serum carbamazepine levels).
Measures to Accelerate Elimination:
The data on
use of dialysis to enhance elimination in carbamazepine is scarce. Dialysis,
particularly high flux or high efficiency hemodialysis, may be considered in
patients with severe carbamazepine poisoning associated with renal failure or in
cases of status epilepticus, or where there are rising serum drug levels and
worsening clinical status despite appropriate supportive care and gastric
decontamination. For severe cases of carbamazepine overdose unresponsive to
other measures, charcoal hemoperfusion may be used to enhance drug
clearance.
Respiratory Depression: Keep the airways free;
resort, if necessary, to endotracheal intubation, artificial respiration, and
administration of oxygen.
Hypotension, Shock: Keep the patient’s legs raised
and administer a plasma expander. If blood pressure fails to rise despite
measures taken to increase plasma volume, use of vasoactive substances should be
considered.
Convulsions: Diazepam or barbiturates.
Warning: Diazepam or barbiturates may aggravate
respiratory depression (especially in children), hypotension, and coma. However,
barbiturates should not be used if drugs that
inhibit monoamine oxidase have also been taken by the patient either in
overdosage or in recent therapy (within 1 week).
Surveillance:Respiration, cardiac function (ECG
monitoring), blood pressure, body temperature, pupillary reflexes, and kidney
and bladder function should be monitored for several days.
Treatment of Blood Count Abnormalities: If evidence
of significant bone marrow depression develops, the following recommendations
are suggested: (1) stop the drug, (2) perform daily CBC, platelet, and
reticulocyte counts, (3) do a bone marrow aspiration and trephine biopsy
immediately and repeat with sufficient frequency to monitor recovery.
Special periodic studies might be helpful as follows: (1) white cell and
platelet antibodies, (2)59Fe-ferrokinetic studies, (3)
peripheral blood cell typing, (4) cytogenetic studies on marrow and peripheral
blood, (5) bone marrow culture studies for colony-forming units, (6) hemoglobin
electrophoresis for A2 and F hemoglobin, and (7) serum
folic acid and B12 levels.
A fully developed aplastic anemia will require appropriate, intensive
monitoring and therapy, for which specialized consultation should be sought.
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