doxepin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tricyclic compounds 956 1668-19-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • P-3693A
  • doxepin
  • doxepine
  • doxepin hydrochloride
  • silenor
  • doxepin HCl
A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.
  • Molecular weight: 279.38
  • Formula: C19H21NO
  • CLOGP: 4.09
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 0
  • TPSA: 12.47
  • ALOGS: -3.94
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 17.90 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 30 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 12 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.20 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 23, 1969 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Completed suicide 1553.39 65.87 337 843 20697 2336208
Toxicity to various agents 1056.74 65.87 270 910 32484 2324421
Cardio-respiratory arrest 427.00 65.87 103 1077 9043 2347862
Drug abuse 384.30 65.87 100 1080 11926 2344979
Respiratory arrest 331.37 65.87 78 1102 6100 2350805
Cardiac arrest 312.24 65.87 89 1091 14841 2342064
Suicide attempt 261.53 65.87 73 1107 11209 2345696
Coma 253.49 65.87 68 1112 8988 2347917
Overdose 245.10 65.87 79 1101 19828 2337077
Intentional overdose 224.96 65.87 65 1115 11256 2345649
Respiratory depression 189.98 65.87 41 1139 2129 2354776
Death 176.92 65.87 93 1087 81375 2275530
Drug hypersensitivity 163.40 65.87 74 1106 46569 2310336
Depressed level of consciousness 138.93 65.87 41 1139 7563 2349342
Bradycardia 127.94 65.87 41 1139 9940 2346965
Poisoning 121.72 65.87 30 1150 2790 2354115
Metabolic acidosis 112.37 65.87 33 1147 5965 2350940
Intentional product misuse 109.44 65.87 36 1144 9453 2347452
Somnolence 107.01 65.87 45 1135 23440 2333465
Tachycardia 100.78 65.87 39 1141 16370 2340535
Sleep-related eating disorder 87.80 65.87 14 1166 128 2356777
Arrhythmia 82.22 65.87 26 1154 6002 2350903
Electrocardiogram QRS complex prolonged 80.62 65.87 18 1162 1084 2355821
Hypotension 72.40 65.87 38 1142 32398 2324507
Insomnia 71.52 65.87 35 1145 25752 2331153
Loss of consciousness 69.12 65.87 31 1149 18736 2338169
Bradypnoea 66.06 65.87 13 1167 421 2356484

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Completed suicide 977.34 68.33 221 514 16091 1729955
Toxicity to various agents 621.05 68.33 174 561 28967 1717079
Drug abuse 474.01 68.33 121 614 13568 1732478
Overdose 199.25 68.33 65 670 16636 1729410
Cardio-respiratory arrest 155.62 68.33 47 688 9246 1736800
Intentional overdose 142.21 68.33 42 693 7628 1738418
Cardiac arrest 126.95 68.33 46 689 15884 1730162
Death 126.58 68.33 77 658 87366 1658680
Intentional product misuse 109.24 68.33 34 701 7324 1738722
Respiratory arrest 103.78 68.33 31 704 5808 1740238
Suicide attempt 100.76 68.33 32 703 7349 1738697
Somnolence 81.93 68.33 34 701 16705 1729341
Coma 69.05 68.33 24 711 7238 1738808

Pharmacologic Action:

SourceCodeDescription
ATC D04AX01 DERMATOLOGICALS
ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
Other antipruritics
ATC N06AA12 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Non-selective monoamine reuptake inhibitors
FDA EPC N0000175752 Tricyclic Antidepressant
CHEBI has role CHEBI:35469 antidepressant
MeSH PA D000928 Antidepressive Agents
MeSH PA D000929 Antidepressive Agents, Tricyclic
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018494 Histamine Agents
MeSH PA D006633 Histamine Antagonists
MeSH PA D006993 Hypnotics and Sedatives
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D000068776 Sleep Aids, Pharmaceutical

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Atopic dermatitis indication 24079001 DOID:3310
Depressive disorder indication 35489007
Anxiety indication 48694002
Lichen simplex chronicus indication 53891004
Severe major depression with psychotic features indication 73867007
Bipolar affective disorder, current episode depression indication 191627008 DOID:3312
Insomnia indication 193462001
Itching of skin indication 418363000
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Orthostatic hypotension contraindication 28651003
Torsades de pointes contraindication 31722008
Hyperthyroidism contraindication 34486009 DOID:7998
Conduction disorder of the heart contraindication 44808001
Hepatic failure contraindication 59927004
Sleep apnea contraindication 73430006 DOID:0050847
Chronic idiopathic constipation contraindication 82934008
Open-angle glaucoma contraindication 84494001 DOID:1067
Epilepsy contraindication 84757009 DOID:1826
Prolonged QT interval contraindication 111975006
Bipolar affective disorder, current episode manic contraindication 191618007
Sleep automatism contraindication 247962006
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Syncope contraindication 271594007
Angle-closure glaucoma contraindication 392291006 DOID:13550
Breastfeeding (mother) contraindication 413712001
Myocardial infarction in recovery phase contraindication 418044006
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.66 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 6211229 Feb. 17, 2020 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 6211229 Feb. 17, 2020 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 10238620 May 18, 2027 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9486437 May 18, 2027 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9861607 May 18, 2027 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 10238620 May 18, 2027 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9486437 May 18, 2027 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9861607 May 18, 2027 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9572814 July 20, 2027 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9572814 July 20, 2027 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 7915307 Aug. 24, 2027 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 7915307 Aug. 24, 2027 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 10548871 April 11, 2028 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 10548871 April 11, 2028 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9107898 May 1, 2028 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 9107898 May 1, 2028 TREATMENT OF INSOMNIA
EQ 3MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 8513299 Sept. 7, 2030 TREATMENT OF INSOMNIA
EQ 6MG BASE SILENOR CURRAX N022036 March 17, 2010 RX TABLET ORAL 8513299 Sept. 7, 2030 TREATMENT OF INSOMNIA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 7.53 WOMBAT-PK CHEMBL
Histamine H1 receptor GPCR ANTAGONIST Ki 9.75 WOMBAT-PK DRUG LABEL
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 6.58 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.33 DRUG MATRIX
Histamine H2 receptor GPCR Ki 5.74 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 7.37 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 6.98 CHEMBL
5-hydroxytryptamine receptor 2B GPCR EC50 7.20 WOMBAT-PK
5-hydroxytryptamine receptor 2C GPCR EC50 7 WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR EC50 7.45 WOMBAT-PK
Alpha-2C adrenergic receptor GPCR IC50 7 WOMBAT-PK
Muscarinic acetylcholine receptor M5 GPCR Ki 7.12 WOMBAT-PK
Muscarinic acetylcholine receptor M4 GPCR Ki 7.09 WOMBAT-PK
Muscarinic acetylcholine receptor M3 GPCR Ki 7.28 WOMBAT-PK
Muscarinic acetylcholine receptor M1 GPCR Ki 7.42 WOMBAT-PK
Histamine H4 receptor GPCR EC50 6.79 WOMBAT-PK
Alpha-2B adrenergic receptor GPCR IC50 7.21 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR Ki 7.63 WOMBAT-PK
5-hydroxytryptamine receptor 7 GPCR WOMBAT-PK
Sodium-dependent serotonin transporter Transporter INHIBITOR Kd 7.17 WOMBAT-PK
D(2) dopamine receptor GPCR EC50 6.50 WOMBAT-PK
D(1A) dopamine receptor GPCR EC50 6.50 WOMBAT-PK
Muscarinic acetylcholine receptor M2 GPCR Ki 6.80 WOMBAT-PK
5-hydroxytryptamine receptor 1A GPCR Ki 6.54 WOMBAT-PK
Solute carrier family 22 member 2 Transporter IC50 4.89 WOMBAT-PK
Alpha-2A adrenergic receptor GPCR Ki 6.30 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 7.48 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 11 CHEMBL
Serotonin (5-HT) receptor GPCR IC50 6.70 CHEMBL

External reference:

IDSource
D004316 MESH_DESCRIPTOR_UI
4019736 VUID
N0000147828 NUI
C0013085 UMLSCUI
D00814 KEGG_DRUG
3U9A0FE9N5 UNII
1229-29-4 SECONDARY_CAS_RN
1855 INN_ID
11841005 SNOMEDCT_US
3638 RXNORM
372587005 SNOMEDCT_US
d00217 MMSL
278670 MMSL
4019736 VANDF
27123 MMSL
004607 NDDF
CHEBI:4710 CHEBI
DB01142 DRUGBANK_ID
1225 IUPHAR_LIGAND_ID
667477 PUBCHEM_CID
CHEMBL1628227 ChEMBL_ID
CHEMBL1628234 ChEMBL_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Doxepin HUMAN PRESCRIPTION DRUG LABEL 1 0228-3315 TABLET, FILM COATED 3 mg ORAL ANDA 18 sections
Doxepin HUMAN PRESCRIPTION DRUG LABEL 1 0228-3316 TABLET, FILM COATED 6 mg ORAL ANDA 18 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-1049 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-3125 CAPSULE 25 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-4250 CAPSULE 50 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-4810 TABLET 3 mg ORAL NDA authorized generic 18 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-4811 TABLET 6 mg ORAL NDA authorized generic 18 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-5375 CAPSULE 75 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-6410 CAPSULE 100 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-8117 CREAM 50 mg TOPICAL NDA authorized generic 12 sections
Zonalon HUMAN PRESCRIPTION DRUG LABEL 1 0378-8123 CREAM 50 mg TOPICAL NDA 12 sections
PRUDOXIN HUMAN PRESCRIPTION DRUG LABEL 1 0378-8130 CREAM 50 mg TOPICAL NDA 12 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6970 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6971 CAPSULE 25 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6972 CAPSULE 50 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6973 CAPSULE 100 mg ORAL ANDA 13 sections
DOXEPIN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 16590-081 CAPSULE 50 mg ORAL ANDA 13 sections
DOXEPIN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 16590-631 CAPSULE 10 mg ORAL ANDA 13 sections
DOXEPIN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 16590-764 CAPSULE 100 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-441 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 21695-943 CAPSULE 50 mg ORAL ANDA 13 sections
Doxepin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 27241-167 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 27241-168 CAPSULE 25 mg ORAL ANDA 13 sections
Doxepin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 27241-169 CAPSULE 50 mg ORAL ANDA 13 sections
Doxepin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 27241-170 CAPSULE 75 mg ORAL ANDA 13 sections
Doxepin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 27241-171 CAPSULE 100 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 35356-650 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-247 CAPSULE 150 mg ORAL ANDA 13 sections
DOXEPIN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 42549-492 CAPSULE 150 mg ORAL ANDA 13 sections
Silenor HUMAN PRESCRIPTION DRUG LABEL 1 42847-103 TABLET 3 mg ORAL NDA 18 sections