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Toxic manifestations of amoxapine (amoxapine (amoxapine tablets) tablets) overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects - particularly grand mal convulsions - occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Fatal overdoses with amoxapine (amoxapine (amoxapine tablets) tablets) have occurred.
Renal failure may develop two to five days after toxic overdosage in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomyolysis and myoglobinuria is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.
Treatment of amoxapine (amoxapine (amoxapine tablets) tablets) overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures. If the patient is conscious, induced emesis followed by gastric lavage with appropriate precautions to prevent pulmonary aspiration should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption, and repeated administrations may facilitate drug elimination. An adequate airway should be established in comatose patients and assisted ventilation instituted if necessary. Seizures may respond to standard anticonvulsant therapy such as intravenous diazepam and/or phenytoin. The value of physostigmine appears less certain. Status epilepticus, should it develop, requires vigorous treatment such as that described by Delgado- Escueta et al ( N Engl J Med 1982; 306:1337-1340).
Convulsions, when they occur, typically begin within 12 hours after ingestion. Because seizures may occur precipitously in some overdosage patients who appear otherwise relatively asymptomatic, the treating physician may wish to consider prophylactic administration of anticonvulsant medication during this period.
Treatment of renal impairment, should it occur, is the same as that for nondrug-induced renal dysfunction.
Serious cardiovascular effects are rare following amoxapine (amoxapine (amoxapine tablets) tablets) overdosage, and the ECG typically remains within normal limits except for sinus tachycardia. Hence, prolongation of the QRS interval beyond 100 milliseconds within the first 24 hours is not a useful guide to the severity of overdosage with this drug.
Fatalities and neurologic sequelae have resulted from prolonged status epilepticus in amoxapine (amoxapine (amoxapine tablets) tablets) overdosage patients. While the lethal dose appears higher than that of other tricyclic antidepressants (80% of lethal amoxapine (amoxapine (amoxapine tablets) tablets) overdosages have involved ingestion of 3 grams or more), many factors other than amount ingested are important in assessing probability of survival. These include age and physical condition of the patient, concomitant ingestion of other drugs, and especially the interval between drug ingestion and initiation of emergency treatment.
Amoxapine (amoxapine (amoxapine tablets) tablets) is contraindicated in patients who have shown prior hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants and monoamine oxidase inhibitors simultaneously. When it is desired to replace a monoamine oxidase inhibitor with amoxapine (amoxapine (amoxapine tablets) tablets) , a minimum of 14 days should be allowed to elapse after the former is discontinued. Amoxapine (amoxapine (amoxapine tablets) tablets) should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. The drug is not recommended for use during the acute recovery phase following myocardial infarction.
Last reviewed on RxList: 7/1/2008
This monograph has been modified to include the generic and brand name in many instances.
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