Source: FDA, National Drug Code (US) Revision Year: 2015
Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation.
Effective dosage of amoxapine may vary from one patient to another. Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily. Hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have dosage raised cautiously up to 600 mg daily in divided doses.
Amoxapine may be given in a single daily dose, not to exceed 300 mg, preferably at bedtime. If the total daily dosage exceeds 300 mg, it should be given in divided doses.
Usual starting dosage is 50 mg two or three times daily. Depending upon tolerance, dosage may be increased to 100 mg two or three times daily by the end of the first week. (Initial dosage of 300 mg daily may be given, but notable sedation may occur in some patients during the first few days of therapy at this level.) Increases above 300 mg daily should be made only if 300 mg daily has been ineffective during a trial period of at least two weeks. When effective dosage is established, the drug may be given in a single dose (not to exceed 300 mg) at bedtime.
In general, lower dosages are recommended for these patients. Recommended starting dosage of amoxapine is 25 mg two or three times daily. If no intolerance is observed, dosage may be increased by the end of the first week to 50 mg two or three times daily. Although 100 to 150 mg daily may be adequate for many elderly patients, some may require higher dosage. Careful increases up to 300 mg daily are indicated in such cases.
Once an effective dosage is established, amoxapine may conveniently be given in a single bedtime dose, not to exceed 300 mg.
Recommended maintenance dosage of amoxapine is the lowest dose that will maintain remission. If symptoms reappear, dosage should be increased to the earlier level until they are controlled.
For maintenance therapy at dosages of 300 mg or less, a single dose at bedtime is recommended.
Toxic manifestations of amoxapine 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 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 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 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 overdosage patients. While the lethal dose appears higher than that of other tricyclic antidepressants (80% of lethal amoxapine 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.
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature].
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