doxepin indications/contra

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

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P

Approvals:

DateAgencyCompanyOrphan
Sept. 23, 1969 FDA

FDA Adverse Event Reporting System

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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 2038.27 56.73 450 1090 30664 3353655
Toxicity to various agents 905.66 56.73 259 1281 46795 3337524
Drug abuse 743.08 56.73 183 1357 18147 3366172
Respiratory arrest 491.32 56.73 120 1420 11248 3373071
Overdose 481.86 56.73 149 1391 33829 3350490
Cardiac arrest 478.28 56.73 141 1399 27178 3357141
Cardio-respiratory arrest 364.92 56.73 101 1439 15339 3368980
Intentional overdose 338.61 56.73 95 1445 15130 3369189
Death 331.05 56.73 172 1368 152152 3232167
Suicide attempt 298.85 56.73 87 1453 15760 3368559
Poisoning 209.81 56.73 52 1488 5060 3379259
Intentional product misuse 188.14 56.73 58 1482 12643 3371676
Coma 180.33 56.73 56 1484 12496 3371823
Somnolence 135.45 56.73 58 1482 32146 3352173
Drug hypersensitivity 117.02 56.73 54 1486 35626 3348693
Drug interaction 100.23 56.73 53 1487 46759 3337560
Electrocardiogram QRS complex prolonged 72.06 56.73 17 1523 1329 3382990
Tachycardia 69.12 56.73 33 1507 23338 3360981
Bradycardia 66.50 56.73 29 1511 16640 3367679
Seizure 65.10 56.73 38 1502 40362 3343957
Exposure via ingestion 60.16 56.73 15 1525 1478 3382841
Generalised tonic-clonic seizure 60.05 56.73 22 1518 8020 3376299
Electrocardiogram QT prolonged 57.20 56.73 23 1517 10772 3373547

Pharmacologic Action:

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SourceCodeDescription
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 D018494 Histamine Agents
MeSH PA D006633 Histamine Antagonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D000068776 Sleep Aids, Pharmaceutical

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Atopic dermatitis indication 24079001 DOID:3310
Depressive disorder indication 35489007 DOID:2848
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:0050848
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 DOID:2883
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

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.66 Basic

Orange Book patent data (new drug applications)

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

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Histamine H1 receptor GPCR ANTAGONIST Ki 9.75 WOMBAT-PK DRUG LABEL
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 7.53 WOMBAT-PK CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 6.30 DRUG MATRIX
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
Muscarinic acetylcholine receptor M4 GPCR Ki 7.09 WOMBAT-PK
5-hydroxytryptamine receptor 6 GPCR Ki 6.98 CHEMBL
5-hydroxytryptamine receptor 2C GPCR EC50 7 WOMBAT-PK
5-hydroxytryptamine receptor 2B GPCR EC50 7.20 WOMBAT-PK
Solute carrier family 22 member 2 Transporter IC50 4.89 WOMBAT-PK
Alpha-2C adrenergic receptor GPCR IC50 7 WOMBAT-PK
Muscarinic acetylcholine receptor M5 GPCR Ki 7.12 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
5-hydroxytryptamine receptor 2A GPCR EC50 7.45 WOMBAT-PK
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:

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IDSource
1225 IUPHAR_LIGAND_ID
4019736 VUID
N0000147828 NUI
C0013085 UMLSCUI
D00814 KEGG_DRUG
3U9A0FE9N5 UNII
1229-29-4 SECONDARY_CAS_RN
1855 INN_ID
667477 PUBCHEM_CID
3638 RXNORM
11841005 SNOMEDCT_US
372587005 SNOMEDCT_US
d00217 MMSL
4019736 VANDF
27123 MMSL
N0000006791 NDFRT
N0000147828 NDFRT
004607 NDDF
CHEBI:4710 CHEBI
D004316 MESH_DESCRIPTOR_UI
DB01142 DRUGBANK_ID
CHEMBL1628227 ChEMBL_ID
CHEMBL1628234 ChEMBL_ID
5EH PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
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 0378-5375 CAPSULE 75 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-6410 CAPSULE 100 mg ORAL ANDA 13 sections
Zonalon HUMAN PRESCRIPTION DRUG LABEL 1 10337-804 CREAM 50 mg TOPICAL NDA 12 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 24236-045 CAPSULE 100 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24236-048 CAPSULE 75 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 24236-115 CAPSULE 50 mg ORAL ANDA 13 sections
Zonalon HUMAN PRESCRIPTION DRUG LABEL 1 35356-043 CREAM 50 mg TOPICAL NDA 12 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 35356-650 CAPSULE 10 mg ORAL ANDA 13 sections
PRUDOXIN HUMAN PRESCRIPTION DRUG LABEL 1 40076-511 CREAM 50 mg TOPICAL NDA 12 sections
Zonalon HUMAN PRESCRIPTION DRUG LABEL 1 40076-715 CREAM 50 mg TOPICAL NDA 12 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 40085-716 CREAM 50 mg TOPICAL NDA AUTHORIZED GENERIC 12 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
Silenor HUMAN PRESCRIPTION DRUG LABEL 1 42847-106 TABLET 6 mg ORAL NDA 18 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43063-217 CAPSULE 25 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-329 CAPSULE 10 mg ORAL ANDA 14 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-331 CAPSULE 25 mg ORAL ANDA 14 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45865-775 CAPSULE 10 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45865-849 CAPSULE 100 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49349-117 CAPSULE 25 mg ORAL ANDA 13 sections
Doxepin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49349-865 CAPSULE 10 mg ORAL ANDA 13 sections