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Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11465523 | https://www.drugs.com/monograph/doxepin-hydrochloride.html | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa69c63c-ced6-4676-a16b-554f1af7d210

Doxepin is a dibenzoxepin tricyclic antidepressant marketed worldwide. It is a white crystalline solid readily soluble in water, lower alcohols and chloroform. The mechanism of action of doxepin is not definitely known. It is not a central nervous system stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the clinical effects are due, at least in part, to influences on the adrenergic activity at the synapses so that deactivation of norepinephrine by reuptake into the nerve terminals is prevented. Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders. Drowsiness is the most commonly noticed side effect. This tends to disappear as therapy is continued. Other infrequently reported CNS side effects are confusion, disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor. : Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported occasionally. Skin rash, edema, photosensitization, and pruritus have occasionally occurred. Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura. Doxepin is used to treat depression, anxiety disorders, itchiness, trouble sleeping, and as a second-line treatment of chronic idiopathic urticaria (hives). Its oral formulations are FDA-approved for the treatment of depression, anxiety, and insomnia and its topical formulations are FDA-approved the short-term management (up to 8 days) of atopic dermatitis and lichen simplex chronicus. Whereas in Australia and the UK, the only licensed indication(s) is/are in the treatment of major depression and pruritus in eczema, respectively.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SINEQUAN

Approved Use

INDICATIONS & USAGE Doxepin is recommended for the treatment of: Psychoneurotic patients with depression and/or anxiety. Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol). Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly). Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. The target symptoms of psychoneurosis that respond particularly well to doxepin include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry. Clinical experience has shown that doxepin is safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin is not recommended for use in children under 12 years of age.

Launch Date

1969
Primary
SINEQUAN

Approved Use

INDICATIONS & USAGE Doxepin is recommended for the treatment of: Psychoneurotic patients with depression and/or anxiety. Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol). Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly). Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. The target symptoms of psychoneurosis that respond particularly well to doxepin include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry. Clinical experience has shown that doxepin is safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin is not recommended for use in children under 12 years of age.

Launch Date

1969
Primary
ZONALON

Approved Use

INDICATIONS & USAGE Zonalon Cream is indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus.

Launch Date

1994
PubMed

PubMed

TitleDatePubMed
A review of clinical studies with combinations of fluphenazine and nortriptyline.
1972
Effect of beta-adrenoceptor blocking drugs, physostigmine, and atropine on the toxicity of doxepin in mice.
1975 Aug
Tricyclic-induced myoclonus.
1977 Jan
Delirium after abrupt withdrawal from doxepin: case report.
1980 Feb
Transient ophthalmoparesis with doxepin overdosage.
1981 Jun
Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.
1985 Feb
A comparative trial of the antidepressant, anxiolytic, and cardiovascular effects of trimipramine and doxepin in depressed hospitalized patients.
1985 Mar
Dystonic reactions to amitriptyline and doxepin.
1988 May
Doxepin in the treatment of female detrusor overactivity: a randomized double-blind crossover study.
1989 Oct
Serious adverse effects of combining fluoxetine and tricyclic antidepressants.
1990 Apr
Protracted ventricular arrhythmias occurring after abrupt tricyclic antidepressant withdrawal.
1990 Fall
Possible induction of mania by buspirone.
1990 Jan
Bupropion-induced carbohydrate craving and weight gain.
1992 Oct
Doxepin-induced recurrent acute hepatitis.
1993 Oct
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
1997 Dec 11
Electrocardiographic effects of fluoxetine and doxepin in patients with major depressive disorder.
1997 Feb
Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.
2004
'Hypnotic' prescription patterns in a large managed-care population.
2004 Sep
Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy.
2008 Mar-Apr
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20126slr006_Zonalon_lbl.pdf
For Mild Anxiety: Initial dose: 25 mg per day in 1 to 3 divided doses. Maintenance dose: 25 to 50 mg per day in 1 to 3 divided doses. For Moderate Anxiety: Initial dose: 75 mg per day in 1 to 3 divided doses. Maintenance dose: 75 to 150 mg per day in 1 to 3 divided doses. For Severe Anxiety: Initial dose: 150 mg per day in 1 to 3 divided doses. Maintenance dose: 150 to 300 mg per day in 1 to 3 divided doses. The maximum single dose should not exceed 150 mg. For treatment moderate pruritus A thin film of Doxepin should be applied four times each day with at least a 3 to 4 hour interval between applications. There are no data to establish the safety and effectiveness of Doxepin when used for greater than 8 days. Chronic use beyond eight days may result in higher systemic levels and should be avoided.
Route of Administration: Other
In Vitro Use Guide
Doxepin effects were studied on rat vas deferens responses to noradrenaline. Tissues were prepared in Krebs-Henseleit solution. In normal Krebs-Henseleit solution doxepin behaved as competitive antagonists.
Substance Class Mixture
Created
by admin
on Mon Mar 31 18:30:30 GMT 2025
Edited
by admin
on Mon Mar 31 18:30:30 GMT 2025
Record UNII
5ASJ6HUZ7D
Record Status FAILED
Record Version
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Name Type Language
DOXEPIN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
1-PROPANAMINE, 3-DIBENZ(B,E)OXEPIN-11(6H)-YLIDENE-N,N-DIMETHYL-
Preferred Name English
DOXEPIN [VANDF]
Common Name English
DOXEPINE
Common Name English
Doxepin [WHO-DD]
Common Name English
DOXEPIN IS A CIS-TRANS (APPROXIMATELY 1:5) MIXTURE
Common Name English
DOXEPIN [MI]
Common Name English
3-DIBENZO(B,E)OXEPIN-11(6H)-YLIDENE-N,N-DIMETHYLPROPAN-1-AMINE
Common Name English
DOXEPIN [HSDB]
Common Name English
doxepin [INN]
Common Name English
Classification Tree Code System Code
WHO-VATC QN06AA12
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
WHO-ATC N06AA12
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
LIVERTOX NBK548035
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WHO-ATC D04AX01
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NCI_THESAURUS C94727
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NDF-RT N0000175752
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
Code System Code Type Description
RXCUI
3638
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PRIMARY RxNorm
MERCK INDEX
m4753
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PRIMARY Merck Index
EVMPD
SUB06387MIG
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
WIKIPEDIA
DOXEPIN
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
DAILYMED
5ASJ6HUZ7D
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
DRUG BANK
DB01142
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PRIMARY
INN
1855
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PRIMARY
CHEBI
4710
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PRIMARY
IUPHAR
1225
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PRIMARY
CAS
1668-19-5
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PRIMARY
DRUG CENTRAL
956
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PRIMARY
MESH
D004316
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
NCI_THESAURUS
C65475
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PRIMARY
ChEMBL
CHEMBL1628227
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
PUBCHEM
3158
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
SMS_ID
100000080813
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
FDA UNII
5ASJ6HUZ7D
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
LACTMED
Doxepin
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
EPA CompTox
DTXSID7022966
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
HSDB
3069
Created by admin on Mon Mar 31 18:30:30 GMT 2025 , Edited by admin on Mon Mar 31 18:30:30 GMT 2025
PRIMARY
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