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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

-8.64E9
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

-8.64E9
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

7.6515842E11
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
A controlled comparison of doxepin h.s. and doxepin q.i.d.
1975 Jul
Tricyclic-induced myoclonus.
1977 Jan
Hoarseness and aphonia as a side effect of tricyclic antidepressants.
1979 Dec
Comparison of the cardiovascular toxicity of three tricyclic antidepressant drugs: imipramine, amitriptyline, and doxepin.
1979 Mar
Hypertensive crisis possibly due to drug interaction.
1979 Nov
Delirium associated with sulindac.
1980 Apr 25
Delirium after abrupt withdrawal from doxepin: case report.
1980 Feb
A comparative study of the therapeutic effect and cardiotoxicity of dothiepin HCl and doxepin HCl in reactive depression.
1981
Transient ophthalmoparesis with doxepin overdosage.
1981 Jun
Tricyclic antidepressants and cardiac arrhythmias during halothane-pancuronium anesthesia.
1981 Mar-Apr
Doxepin and visual hallucinations.
1982 Dec
Doxepin induced torsade de pointes.
1982 Nov
Therapeutic superiority of maprotiline versus doxepin in geriatric depression.
1983 Dec
Doxepin and tinnitus.
1983 Sep
Bilateral internuclear ophthalmoplegia from doxepin overdose.
1984 Feb
Neuropathy and fatal hepatitis in a patient receiving amiodarone.
1984 Jun 2
Orthostatic effect of imipramine and doxepin in depressed geriatric outpatients.
1985 Apr
Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.
1985 Feb
Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder.
1985 Mar
A comparative trial of the antidepressant, anxiolytic, and cardiovascular effects of trimipramine and doxepin in depressed hospitalized patients.
1985 Mar
Seizures with neuroleptics and antidepressants.
1987 Mar
Acute effects of maprotiline, doxepin and zimeldine with alcohol in healthy volunteers.
1988 Jan-Feb
Dystonic reactions to amitriptyline and doxepin.
1988 May
A case of immune complex hemolytic anemia, thrombocytopenia, and acute renal failure associated with doxepin use.
1989 Mar
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
Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes.
1992 May
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
Focal cortical transient preceding myoclonus during lithium and tricyclic antidepressant therapy.
1999 Jan 1
Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).
2000 Jan
[Valproic acid in prophylaxis of bipolar disorder. A case of valproate-induced encephalopathy].
2000 May
National Patterns of Medication Treatment for Depression, 1987 to 2001.
2001 Dec
Influence of doxepin used in preemptive analgesia on the nociception in the perioperative period. Experimental and clinical study.
2001 May-Jun
Doxepin-induced torsade de pointes tachycardia.
2001 Sep 4
A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors.
2002 Jul
Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species.
2004 May
'Hypnotic' prescription patterns in a large managed-care population.
2004 Sep
Antidepressant-associated chronic irritable dysphoria (acid) in bipolar disorder: a case series.
2005 Feb
QT prolongation and syncope with methadone, doxepin, and a beta-blocker.
2005 Oct
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
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 Sat Jun 26 17:11:02 UTC 2021
Edited
by admin
on Sat Jun 26 17:11:02 UTC 2021
Record UNII
5ASJ6HUZ7D
Record Status Validated (UNII)
Record Version
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Name Type Language
DOXEPIN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
DOXEPIN [VANDF]
Common Name English
DOXEPINE
Common Name English
DOXEPIN IS A CIS-TRANS (APPROXIMATELY 1:5) MIXTURE
Common Name English
DOXEPIN [WHO-DD]
Common Name English
DOXEPIN [MI]
Common Name English
3-DIBENZO(B,E)OXEPIN-11(6H)-YLIDENE-N,N-DIMETHYLPROPAN-1-AMINE
Common Name English
1-PROPANAMINE, 3-DIBENZ(B,E)OXEPIN-11(6H)-YLIDENE-N,N-DIMETHYL-
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 Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
WHO-ATC N06AA12
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
LIVERTOX 326
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
WHO-ATC D04AX01
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
NCI_THESAURUS C94727
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
NDF-RT N0000175752
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
Code System Code Type Description
RXCUI
3638
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M4753
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY Merck Index
EVMPD
SUB06387MIG
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
WIKIPEDIA
DOXEPIN
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
DRUG BANK
DB01142
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
INN
1855
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
IUPHAR
1225
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
CAS
1668-19-5
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
DRUG CENTRAL
956
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
MESH
D004316
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
NCI_THESAURUS
C65475
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
ChEMBL
CHEMBL1628227
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
FDA UNII
5ASJ6HUZ7D
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
LACTMED
Doxepin
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
EPA CompTox
1668-19-5
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
HSDB
3069
Created by admin on Sat Jun 26 17:11:03 UTC 2021 , Edited by admin on Sat Jun 26 17:11:03 UTC 2021
PRIMARY
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