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Amoxapine
Brand name (Asendin)
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Symptoms:
Toxic manifestations of overdosage differ significantly from those of other tricyclic antidepressants. CNS effects such as drowsiness, delirium, lethargy with diminished deep tendon reflexes and 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 overdosage in some cases.
Fatalities have resulted from amoxapine overdosage and permanent neurologic damage has occurred in some patients who recovered after prolonged status epilepticus and severe acidosis.
Renal failure may develop 2 to 5 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 typically occurs in those who have experienced multiple seizures, and most patients recover with
appropriate treatment.
Cardiovascular effects, when they occur, are usually limited to sinus tachycardia and transient minor ECG changes. 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 amoxapine. Serious hypotension, hypertension, incomplete bundle branch
block and cardiac arrhythmias have been rarely observed with amoxapine.
The smallest estimated lethal overdoses reported with amoxapine in adults have been 1.5 to 2 g. A 15-month old child died after ingesting approximately 250 mg. On the other hand, some patients have survived much larger overdoses. Age and physical condition of the patient, concomitant ingestion of other drugs, and especially the
interval between drug ingestion and initiation of emergency treatment, are important determining factors in the probability of survival.
Symptoms of overdosage reported with other tricyclic antidepressants include: drowsiness, mydriasis, dysarthria, general weakness, excitement, agitation, hyperactive reflexes, muscle spasms and rigidity, hypothermia, hyperpyrexia, vomiting, perspiration, rapid thready pulse, convulsions, severe hypotension, hypertension, tachycardia,
disturbances of cardiac conduction, arrhythmia, congestive heart failure, circulatory collapse, respiratory depression and coma. In patients with glaucoma, even average doses may precipitate an attack.
Treatment:
Treatment should be symptomatic and supportive, but with special attention to prevention or control of seizures. Renal failure may develop a few days after substantial amoxapine overdosage in patients who may appear otherwise recovered. Therefore, patients who may have ingested an overdosage of amoxapine, particularly children, should be
hospitalized and kept under close surveillance.
In all comatose patients basic life support measures must be instituted, including establishment of an adequate airway and assisted ventilation, if necessary. Emesis should be induced only in conscious, asymptomatic patients. In all other patients, gastric lavage, with appropriate precautions to prevent pulmonary aspiration, should be
performed as soon as possible. These measures are recommended up to 12 hours or even more after the overdose since the anticholinergic effect of the drug may delay gastric emptying. Following lavage or emesis activated charcoal may be administered to reduce absorption, and repeated administration may facilitate drug elimination. Acidosis
may be treated by cautious administration of sodium bicarbonate. Treatment of renal impairment is the same as that for non-drug-induced renal dysfunction. The value of dialysis is doubtful due to the extensive plasma protein binding of amoxapine.
External stimulation should be minimized to reduce the tendency to convulsions. Convulsions, when they occur, typically begin within 12 hours after ingestion of amoxapine. 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. Standard anticonvulsants, such as i.v. diazepam and/or phenytoin should be administered. Barbiturates may intensify respiratory depression, particularly in children, and aggravate hypotension and coma. Paraldehyde may be used in some children to counteract
muscular hypertonus and convulsions with less likelihood of causing respiratory depression. Prompt control of convulsions, including status epilepticus, is essential since they aggravate hypoxia and acidosis and may thereby precipitate cardiac arrhythmias and arrest, as well as cause permanent neurological damage.
ECG monitoring in an intensive care unit is recommended in all patients with tricyclic antidepressant overdosage, although cardiac complications do not appear to be as serious a problem with amoxapine overdosage as with some other tricyclic antidepressants, and the ECG typically remains within normal limits except for sinus
tachycardia.
Shock should be treated with supportive measures such as i.v. fluids, oxygen and corticosteroids. Pressor agents, such as norepinephrine (but not epinephrine), are rarely indicated and should be given only after careful consideration and under continuous monitoring.
The slow i.v. administration of physostigmine salicylate has been reported to reverse most of the cardiovascular and CNS effects of tricyclic overdosage, such as cardiac arrhythmias and convulsions; however, it should not be used routinely because of its short duration of action and potentially serious adverse effects. The recommended
dosage in adults has been 1 to 2 mg in very slow i.v. injection (avoid rapid injection to reduce the possibility of physostigmine-induced convulsions). In children, the initial dosage should not exceed 0.5 mg and should be adjusted to age and response. Singe physostigmine has a short duration of action, administration may have to be
repeated at 30 to 60 minute intervals.
Deaths by deliberate or accidental overdosage have occurred with this class of drugs. Since the propensity for suicide is high in depressed patients, a suicide attempt by other means may occur during the recovery phase. The possibility of simultaneous ingestion of other drugs should also be considered.
The dosage must be individualized according to the requirements of each patient. Treatment should be initiated at the lowest recommended dose and increased gradually with careful assessment of clinical response and any evidence of intolerance. Once effective dosage is well established, the total daily dosage may be given in a single daily
dose (not to exceed 300 mg) at bedtime. Total daily dosages higher than 300 mg should be given in divided doses. Care should be taken not to increase the dosage of amoxapine if manifestations of extrapyramidal effects occur, as there is a possibility of development of tardive dyskinesia with this drug.
Adults:
Initially: 50 mg twice daily. Depending on the patient's tolerance and response, this should be increased to 50 mg 3 times daily as early as the third day of treatment. In severely depressed hospitalized patients or patients under close supervision, a higher initial dose of 50 mg 3 times daily may be indicated, and this may be increased
to 100 mg 2 or 3 times daily. The usual optimum dose is 150 to 300 mg daily, but some patients may require higher doses, up to 400 mg or more daily, depending on tolerance and response of each individual patient. Some hospitalized patients have received doses up to 600 mg daily in divided doses. When higher doses are used, it is essential
to exclude history of convulsive disorders.
Elderly or Debilitated Patients:
The total experience with amoxapine in elderly patients is limited. Therefore, if there is a valid indication for use of amoxapine in an elderly patient, the dosage should be titrated very carefully. As with other drugs of this class, it is recommended to initiate treatment with lower doses and to increase dosage gradually. The
recommended starting dosage is 12.5 mg, 3 times daily. This should be increased very gradually, depending on tolerance and response, to 50 mg 2 or 3 times daily.
Maintenance Dosage:
The recommended maintenance dosage is the lowest dose that will sustain remission. Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement. If symptoms reappear, dosage should be increased to the level which previously induced
remission, until symptoms are again controlled.
When a maintenance dosage has been established as described above, amoxapine may be administered in a single dose before bedtime provided such a dosage regimen is well tolerated. However, if the total daily dose exceeds 300 mg, it should be administered in divided doses.
When amoxapine therapy is discontinued, the withdrawal of the drug should be gradual.
25 mg:
Each heptagonal, white, scored tablet engraved "LL25" and "A13" contains: Amoxapine 25 mg. Tartrazine-free. Bottles of 100.
50 mg:
Each heptagonal, orange, scored tablet engraved "LL50" and "A15" contains: Amoxapine 50 mg. Tartrazine-free. Bottles of 100 and 500.
100 mg:
Each heptagonal, blue, scored tablet engraved "LL100" and "A17" contains: Amoxapine 100 mg. Tartrazine-free. Bottles of 100.
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