Introduction ⬇
VA Class:CN601
AHFS Class:
- Tricyclics and Other Norepinephrine-reuptake Inhibitors 28:16.04.28
Generic Name(s):
Chemical Name:
- 2-Chloro-11-(1-piperazinyl)dibenz[ b,f ][1,4]oxazepine
Molecular Formula:
Amoxapine is a dibenzoxazepine-derivative tricyclic antidepressant.101,106,107,108,116
Uses ⬆ ⬇
Amoxapine shares the pharmacologic actions of the other tricyclic antidepressants and is used in the treatment of neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.101,106,107,108 Most studies comparing amoxapine with amitriptyline or imipramine have not demonstrated superiority of amoxapine over these other tricyclic antidepressants. Although amoxapine has been reported to have a slightly more rapid onset of action than either amitriptyline or imipramine in some studies, this finding has not been adequately established.
Dosage and Administration ⬆ ⬇
Administration 
Amoxapine is administered orally.101,106,107,108 Although amoxapine has been administered in 3 divided doses throughout the day, it is long-acting and, when dosage does not exceed 300 mg daily, the entire daily dose may be administered at one time, preferably at bedtime to avoid daytime sedation.101,106,107,108 When dosage exceeds 300 mg daily, the daily dose should be given in divided doses.101,106,107,108
Dosage
There is a wide range of amoxapine dosage requirements, and dosage of the drug must be carefully individualized.101,106,107,108
Patients should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.106,109,110,111 (See Cautions: Precautions and Contraindications, in the Tricyclic Antidepressants General Statement 28:16.04.28.)
The usual effective dosage of amoxapine is 200-300 mg daily.101,106,107 The usual initial dosage is 100-150 mg daily.101,106,107 Depending on tolerance and response, dosage may be increased to 200-300 mg daily by the end of the first week of therapy.101,106 An initial dosage of 300 mg daily may be given, but considerable sedation may occur in some patients during the first few days of therapy at this dosage level.101,106 If no response occurs after administration of 300 mg of amoxapine daily for at least 2 weeks, dosage may be increased to a maximum of 400 mg daily in outpatients.101,106,107 Hospitalized patients under close supervision may generally be given higher dosages than outpatients; dosage may be increased cautiously up to 600 mg daily in divided doses in hospitalized patients who have not responded adequately and do not have a history of seizures.101,106,107,108 Single doses should not exceed 300 mg.101,106,107
Geriatric patients should usually be given lower than average dosages.101,106,107,108 Therapy usually should be initiated with 50-75 mg daily in these patients and may be increased to 100-150 mg daily by the end of the first week of therapy, if tolerated.101,106,107,108 Some geriatric patients may require further increases in dosa however, dosage in geriatric patients should not exceed 300 mg daily.101,106,107,108
Antidepressant effects usually occur within 2 weeks in most patients who respond to amoxapine therapy and may occur within 4-7 days.101,106,109,113
After symptoms are controlled, dosage should be gradually reduced to the lowest level which will maintain relief of symptoms.101,106
Cautions ⬆ ⬇
Amoxapine shares the toxic potentials of the tricyclic antidepressants, and the usual precautions of tricyclic antidepressant administration should be observed. Patients should be fully advised about the risks, especially suicidal thinking and behavior (suicidality), associated with tricyclic antidepressant therapy.106,110,111 For a complete discussion, see Cautions: Precautions and Contraindications and Cautions: Pediatric Precautions, in the Tricyclic Antidepressants General Statement 28:16.04.28.
Extrapyramidal reactions have occurred in less than 1% of patients receiving amoxapine.101,106 In addition, tardive dyskinesia has been reported rarely in patients receiving the drug.101,106 Like antipsychotic agents, amoxapine has been associated with neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment.101,102,106 For additional information on NMS, see Extrapyramidal Reactions in Cautions: Nervous System Effects, in the Phenothiazines General Statement 28:16.08.24.
Pediatric Precautions
Safety and efficacy of amoxapine for the treatment of depression in children younger than 16 years of age have not been established.101
The US Food and Drug Administration (FDA) has determined that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders.106,110 However, FDA also states that depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.106,110 Anyone considering the use of amoxapine in a child or adolescent for any clinical use must therefore balance the potential risk of therapy with the clinical need.106,110,111,112 (See Cautions: Precautions and Contraindications and Cautions: Pediatric Precautions, in the Tricyclic Antidepressants General Statement 28:16.04.28.)
Other Information ⬆ ⬇
Pharmacokinetics
Absorption
Amoxapine is rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations of amoxapine occur within 1-2 hours after a single oral dose.101,106,107,108,114
Distribution
In rats, amoxapine is widely distributed throughout body tissues, with highest concentrations distributed into lungs, spleen, kidneys, heart, and brain and lower concentrations distributed into testes and muscle.108
Amoxapine is approximately 90% bound to plasma proteins.101,106,107
Amoxapine and 8-hydroxyamoxapine have been detected in human milk in concentrations of approximately one-fifth and one-third those of maternal steady-state serum concentrations, respectively.100,108
Elimination
The plasma half-life of amoxapine is approximately 8 hours.101,106,107,108,114 Amoxapine is metabolized in the liver principally to 8-hydroxyamoxapine and, to a lesser extent, to 7-hydroxyamoxapine; both metabolites are pharmacologically active and have half-lives of 30 hours and 6.5 hours, respectively.101,106,107,108,113,114,115,116
Approximately 60-69% of a dose of amoxapine is excreted in urine within 6 days principally as conjugated metabolites; approximately 7-18% of the drug is excreted in feces principally as unconjugated metabolites.101,106,107,108,114 Less than 5% of amoxapine is excreted in urine as unchanged drug.107,114
Chemistry and Stability
Chemistry
Amoxapine, a tricyclic dibenzoxazepine derivative, is the desmethyl analog of loxapine. Amoxapine differs structurally from the dibenzazepine, dibenzocycloheptene, and dibenzoxepin tricyclic antidepressants in that it has both a nitrogen and an oxygen atom in its 7-membered ring and a piperazinyl ring rather than a propylamino chain attached to the center ring. Amoxapine occurs as a white to pale yellow, crystalline powder and is slightly soluble in water and in alcohol. The drug has an apparent pKa of 7.6.
Stability
Amoxapine tablets should be stored in tight containers at 15-30°C.101
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, and dosage and administration of amoxapine, see the Tricyclic Antidepressants General Statement 28:16.04.28.
Preparations ⬆ ⬇
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Amoxapine
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | Tablets, scored | 25 mg* | Amoxapine Tablets | |
| | 50 mg* | Amoxapine Tablets | |
| | 100 mg* | Amoxapine Tablets | |
| | 150 mg* | Amoxapine Tablets | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Copyright ⬆ ⬇
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions January 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
References ⬆
100. Gelenberg AJ. Amoxapine, a new antidepressant, appears in human milk. J Nerv Ment Dis . 1979; 167:635-6. [PubMed 573779]
101. Lederle Laboratories. Asendin® (amoxapine) prescribing information. Pearl River, NY; 1987 Nov.
102. Lesaca T. Amoxapine and neuroleptic malignant syndrome. Am J Psychiatry . 1987; 144:1514. [PubMed 3118723]
103. Food and Drug Administration. Class suicidality labeling language for antidepressants. From the FDA website. [Web]
104. Food and Drug Administration. Public health advisory: suicidality in children and adolescents being treated with antidepressant medications. Rockville, MD; 2004 Oct 15. From the FDA website. [Web]
105. Food and Drug Administration. Medication guide: about using antidepressants in children or teenagers. Rockville, MD; 2005 Jan 16. From the FDA website. [Web]
106. Watson Laboratories, Inc. Amoxapine tablets prescribing information. Corona, CA; 2007 May.
107. Kinney JL, Evans RL Jr. Evaluation of amoxapine. Clin Pharm. 1982; 1:417-24. [PubMed 6764165]
108. Dugas JE, Weber SS. Amoxapine (Asendin, Lederle Laboratories). Drug Intell Clin Pharm . 1982; 16:199-204. [PubMed 7037342]
109. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
110. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
111. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
112. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA . 2007; 297:1683-96. [PubMed 17440145]
113. Calvo B, Garcia MJ, Pedraz JL et al. Pharmacokinetics of amoxapine and its active metabolites. Int J Clin Pharmacol Ther Toxicol . 1985; 23:180-5. [PubMed 3997304]
114. Greenblatt EN, Hardy RA, Kelly RG. Amoxapine. Pharmacol Biochem Prop Drug Subst . 1979; 2:1-18.
115. Midha KK, Hubbard JW, McKay G et al. The role of metabolites in a bioequivalence study II: amoxapine, 7-hydroxyamoxapine, and 8-hydroxyamoxapine. Int J Clin Pharmacol Ther. 1999; 37:428-38. [PubMed 10507241]
116. Selinger K, Lebel G, Hill HM et al. A high-performance liquid chromatographic method for the analysis of amoxapine in human plasma. J Pharm Biomed Anal . 1989; 7:1001-7. [PubMed 2490101]