esketamine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
4468 33643-46-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • spravato
  • esketamine HCl
  • esketamine hydrochloride
  • esketamine
  • l-Ketamine
Esketamine is the S-enantiomer of racemic ketamine. It is a non-selective, non-competitive, antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. Through NMDA receptor antagonism, esketamine produces a transient increase in glutamate release leading to increases in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) stimulation and subsequently to increases in neurotrophic signalling which may contribute to the restoration of synaptic function in these brain regions involved with the regulation of mood and emotional behaviour. Restoration of dopaminergic neurotransmission in brain regions involved in the reward and motivation, and decreased stimulation of brain regions involved in anhedonia, may contribute to the rapid response.
  • Molecular weight: 237.73
  • Formula: C13H16ClNO
  • CLOGP: 2.93
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 1
  • TPSA: 29.10
  • ALOGS: -3.71
  • ROTB: 2
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
8 mg N

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Dec. 18, 2019 EMA Janssen-Cilag International N.V.
May 3, 2019 FDA JANSSEN PHARMS

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
Dissociation 2191.16 37.29 336 3792 2583 63482311
Sedation 664.23 37.29 196 3932 38613 63446281
Suicidal ideation 656.11 37.29 217 3911 62204 63422690
Suicide attempt 244.35 37.29 105 4023 60813 63424081
Anxiety 156.45 37.29 122 4006 217419 63267475
Dissociative disorder 154.56 37.29 26 4102 361 63484533
Blood pressure increased 93.30 37.29 80 4048 161982 63322912
Underdose 80.15 37.29 38 4090 27418 63457476
Panic attack 74.80 37.29 34 4094 22297 63462597
Euphoric mood 71.60 37.29 22 4106 4865 63480029
Hospitalisation 68.07 37.29 51 4077 85030 63399864
Hypertension 61.80 37.29 83 4045 279220 63205674
Device malfunction 56.06 37.29 26 4102 17831 63467063
Dizziness 53.49 37.29 98 4030 429827 63055067
Product dose omission issue 52.35 37.29 70 4058 234243 63250651
Vomiting 51.01 37.29 112 4016 559505 62925389
Nausea 46.78 37.29 141 3987 854330 62630564
Device issue 38.01 37.29 22 4106 23759 63461135

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
Dissociation 875.07 55.42 136 1627 1522 34953646
Sedation 313.13 55.42 90 1673 20916 34934252
Suicidal ideation 306.09 55.42 103 1660 40285 34914883
Drug ineffective 80.84 55.42 106 1657 456645 34498523
Suicide attempt 79.75 55.42 39 1724 39077 34916091
Blood pressure increased 78.53 55.42 51 1712 88051 34867117
Hypertension 75.44 55.42 59 1704 136384 34818784
Anxiety 72.92 55.42 51 1712 99377 34855791

FDA Adverse Event Reporting System (Geriatric)

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
Dissociation 2363.87 42.02 368 4177 3653 79736190
Sedation 896.09 42.02 256 4289 51639 79688204
Suicidal ideation 786.22 42.02 253 4292 76087 79663756
Suicide attempt 284.13 42.02 123 4422 82809 79657034
Dissociative disorder 177.05 42.02 32 4513 789 79739054
Anxiety 145.38 42.02 117 4428 248395 79491448
Blood pressure increased 135.35 42.02 105 4440 211255 79528588
Hypertension 114.61 42.02 116 4429 330876 79408967
Hospitalisation 100.34 42.02 64 4481 94172 79645671
Underdose 96.59 42.02 44 4501 33107 79706736
Panic attack 82.92 42.02 36 4509 24180 79715663
Dizziness 68.96 42.02 114 4431 526327 79213516
Vomiting 65.24 42.02 127 4418 665701 79074142
Nausea 64.69 42.02 157 4388 957039 78782804
Device malfunction 64.14 42.02 29 4516 21419 79718424
Major depression 57.56 42.02 21 4524 8959 79730884
Euphoric mood 53.01 42.02 19 4526 7707 79732136
Device issue 51.86 42.02 27 4518 27081 79712762
Product dose omission issue 50.24 42.02 66 4479 247471 79492372
Feeling abnormal 49.83 42.02 53 4492 159146 79580697
Completed suicide 47.52 42.02 64 4481 245703 79494140
Drug ineffective 46.88 42.02 151 4394 1080762 78659081

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N01AX14 NERVOUS SYSTEM
ANESTHETICS
ANESTHETICS, GENERAL
Other general anesthetics
ATC N06AX27 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Other antidepressants
MeSH PA D000928 Antidepressive Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D011619 Psychotropic Drugs
CHEBI has role CHEBI:38877 intravenous anesthetics
CHEBI has role CHEBI:60643 N-methyl-D-aspartate receptor antagonists

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Depressive disorder indication 35489007
Arteriovenous malformation contraindication 24551003
Aneurysm contraindication 432119003 DOID:178




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.65 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 9592207 March 20, 2027 TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULT IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 8785500 March 5, 2033 TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULT IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11446260 March 14, 2034 TREATMENT OF DEPRESSIVE SYMPTOMS IN ADULTS WITH MDD WITH ACUTE SUICIDAL IDEATION OR BEHAVIOR BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE AS A PHARMACEUTICAL COMPOSITION TWICE PER WEEK IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11446260 March 14, 2034 TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE AS A PHARMACEUTICAL COMPOSITION IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11446260 March 14, 2034 TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE TWICE PER WEEK AS A PHARMACEUTICAL COMPOSITION IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 10869844 Sept. 10, 2035 TREATMENT OF DEPRESSIVE SYMPTOMS IN ADULTS WITH MDD WITH ACUTE SUICIDAL IDEATION OR BEHAVIOR BY NASALLY ADMINISTERING 56MG OR 84 MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 10869844 Sept. 10, 2035 TREATMENT OF TRD IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS DURING THE INDUCTION PHASE FOLLOWED BY A MAINTENANCE PHASE OF 56MG OR 84 MG WEEKLY OR 1X EVERY TWO WEEKS IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 10869844 Sept. 10, 2035 TREATMENT OF TRD IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS DURING THE INDUCTION PHASE IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11173134 Sept. 10, 2035 TREATMENT OF DEPRESSION IN ADULTS WITH MOD AND ACUTE SUICIDAL IDEATION OR BEHAVIOR IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE IN A MAINTENANCE PHASE WEEKLY OR LX EVERY 2 WEEKS AFTER INDUCTION PHASE
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11173134 Sept. 10, 2035 TREATMENT OF TRD IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE IN A MAINTENANCE PHASE WEEKLY OR 1X EVERY TWO WEEKS TO ADULTS WHO HAVE BEEN ADMINISTERED ESKETAMINE IN A INDUCTION PHASE FOR ABOUT 4 WEEKS
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11311500 Sept. 10, 2035 TREATMENT OF DEPRESSIVE SYMPTOMS IN ADULTS WITH MDD WITH ACUTE SUICIDAL IDEATION OR BEHAVIOR BY NASALLY ADMINISTERING 56MG OR 84 MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11311500 Sept. 10, 2035 TREATMENT OF TRD IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS DURING THE INDUCTION PHASE FOLLOWED BY A MAINTENANCE PHASE OF 56MG OR 84 MG WEEKLY OR 1X EVERY TWO WEEKS IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL 11311500 Sept. 10, 2035 TREATMENT OF TRD IN ADULTS BY NASALLY ADMINISTERING 56MG OR 84MG OF ESKETAMINE 2X WEEKLY FOR 4 WEEKS DURING THE INDUCTION PHASE IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL July 31, 2023 TREATMENT OF SYMPTOMS IN ADULTS WITH MAJOR DEPRESSIVE DISORDER (MDD) WITH ACUTE SUICIDAL IDEATION OR BEHAVIOR.
EQ 28MG BASE SPRAVATO JANSSEN PHARMS N211243 March 5, 2019 RX SPRAY NASAL March 5, 2024 NEW CHEMICAL ENTITY (AN ENANTIOMER OF PREVIOUSLY APPROVED RACEMIC MIXTURE. SEE SECTION 505(U) OF THE FEDERAL FOOD AND DRUG COSMETIC ACT).

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Glutamate NMDA receptor Ion channel ANTAGONIST Ki 6.16 SCIENTIFIC LITERATURE

External reference:

IDSource
D07283 KEGG_DRUG
33643-47-9 SECONDARY_CAS_RN
4038229 VANDF
4038230 VANDF
CHEBI:60799 CHEBI
JC9 PDB_CHEM_ID
CHEMBL395091 ChEMBL_ID
CHEMBL2364609 ChEMBL_ID
C000629870 MESH_SUPPLEMENTAL_RECORD_UI
9152 IUPHAR_LIGAND_ID
7884 INN_ID
DB11823 DRUGBANK_ID
50LFG02TXD UNII
2119365 RXNORM
309966 MMSL
36280 MMSL
d09174 MMSL
015448 NDDF
015449 NDDF
1217154004 SNOMEDCT_US
785816006 SNOMEDCT_US
789486001 SNOMEDCT_US
C2825616 UMLSCUI
182137 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Spravato HUMAN PRESCRIPTION DRUG LABEL 1 49396-0280 SPRAY 28 mg NASAL Export only 1 sections
Spravato HUMAN PRESCRIPTION DRUG LABEL 1 50458-028 SOLUTION 28 mg NASAL NDA 38 sections
Spravato HUMAN PRESCRIPTION DRUG LABEL 1 50458-028 SOLUTION 28 mg NASAL NDA 38 sections