Overview
DESCRIPTION Amoxapine, USP is an antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzazepines, dibenzocycloheptenes, and dibenzoxepines. It is designated chemically as 2-Chloro-11-(1-piperazinyl)dibenz[b,f][1,4]oxazepine. The structural formula is represented below: C 17 H 16 CIN 3 O M.W. 313.
Mechanism of Action
CLINICAL PHARMACOLOGY Amoxapine is an antidepressant with a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of norepinephrine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Amoxapine is absorbed rapidly and reaches peak blood levels approximately 90 minutes after ingestion. It is almost completely metabolized. The main route of excretion is the kidney. In vitro tests show that amoxapine binding to human serum is approximately 90%. In man, amoxapine serum concentration declines with a half-life of eight hours. However, the major metabolite, 8-hydroxy-amoxapine, has a biologic half-life of 30 hours.
Indications
- INDICATIONS AND USAGE 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.
Common Doses
- 300 mg
- 400 mg
- 600 mg
- 50 mg
Dosage
DOSAGE AND ADMINISTRATION 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.
Black Box Warning
Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amoxapine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Contraindications
- CONTRAINDICATIONS Amoxapine 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, a minimum of 14 days should be allowed to elapse after the former is discontinued.
Side Effects
- ADVERSE REACTIONS Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class. Incidence Greater Than 1% The most frequent types of adverse reactions occurring with amoxapine in controlled clinical trials were sedative and anticholinergic: these included drowsiness (14%), dry mouth (14%), constipation (12%), and blurred vision (7%).
Interactions
- Drug Interactions See CONTRAINDICATIONS about concurrent usage of tricyclic antidepressants and monoamine oxidase inhibitors. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic drugs. Amoxapine may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Serum levels of several tricyclic antidepressants have been reported to be significantly increased when cimetidine is administered concurrently.