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

Stem definitionDrug idCAS RN
serotonin and/or norepinephrine reuptake inhibitors, fluoxetine derivatives 4806 508233-74-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • vortioxetine-DL-lactate
  • vortioxetine DL-lactate
  • brintellix
  • Lu AA21004
  • vortioxetine
  • vortioxetine hydrobromide
A piperazine derivative that acts as a serotonin reuptake inhibitor, as a 5-HT3 receptor antagonist, and 5-HT1A receptor agonist. It is used for the treatment of anxiety and depression.
  • Molecular weight: 298.45
  • Formula: C18H22N2S
  • CLOGP: 4.92
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 1
  • TPSA: 15.27
  • ALOGS: -4.92
  • ROTB: 3

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
10 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 35.30 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 5.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 72 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 30, 2013 FDA TAKEDA PHARMS USA
Sept. 20, 2019 PMDA Takeda Pharmaceutical Company Limited

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
Suicidal ideation 408.10 18.75 216 10437 56166 46619243
Nausea 352.07 18.75 586 10067 686868 45988541
Pruritus 199.74 18.75 260 10393 242092 46433317
Suicide attempt 135.22 18.75 107 10546 54929 46620480
No adverse event 118.87 18.75 82 10571 34149 46641260
Serotonin syndrome 113.45 18.75 70 10583 24150 46651259
Anxiety 103.52 18.75 164 10489 181793 46493616
Intentional overdose 87.44 18.75 90 10563 64854 46610555
Anger 87.15 18.75 46 10607 11806 46663603
Mania 85.19 18.75 44 10609 10802 46664607
Irritability 81.35 18.75 61 10592 28885 46646524
Depression 77.61 18.75 139 10514 169965 46505444
Vomiting 69.07 18.75 243 10410 452551 46222858
Feeling abnormal 68.63 18.75 111 10542 124949 46550460
Somnolence 63.94 18.75 122 10531 156399 46519010
Tremor 62.57 18.75 102 10551 115537 46559872
Agitation 54.19 18.75 65 10588 55350 46620059
Abnormal dreams 54.01 18.75 32 10621 10247 46665162
Insomnia 53.64 18.75 117 10536 164807 46510602
Nightmare 53.47 18.75 38 10615 16560 46658849
Drug abuse 47.25 18.75 65 10588 63343 46612066
Sopor 45.33 18.75 37 10616 19791 46655618
Product administered to patient of inappropriate age 43.40 18.75 18 10635 2678 46672731
Sexual dysfunction 41.94 18.75 17 10636 2386 46673023
Wrong technique in product usage process 40.85 18.75 56 10597 54366 46621043
Crying 39.23 18.75 35 10618 21106 46654303
Electrocardiogram QT prolonged 38.81 18.75 53 10600 51272 46624137
Weight increased 37.71 18.75 102 10551 164371 46511038
Intentional self-injury 37.10 18.75 36 10617 24130 46651279
Psychomotor hyperactivity 35.64 18.75 24 10629 9589 46665820
Pneumonia 35.49 18.75 21 10632 376299 46299110
Rheumatoid arthritis 33.52 18.75 7 10646 240208 46435201
Hepatic infiltration eosinophilic 33.09 18.75 6 10647 33 46675376
Akathisia 32.84 18.75 21 10632 7693 46667716
Pregnancy 31.85 18.75 35 10618 27102 46648307
Libido increased 30.57 18.75 10 10643 762 46674647
Product use in unapproved indication 30.39 18.75 65 10588 90208 46585201
Restlessness 28.38 18.75 32 10621 25492 46649917
Energy increased 26.63 18.75 12 10641 2182 46673227
Hallucination, auditory 26.55 18.75 21 10632 10735 46664674
Antipsychotic drug level increased 25.20 18.75 13 10640 3179 46672230
Prescribed overdose 24.94 18.75 20 10633 10429 46664980
Antipsychotic drug level above therapeutic 24.84 18.75 9 10644 932 46674477
Product name confusion 23.89 18.75 5 10648 63 46675346
Lymphocytic hypophysitis 23.72 18.75 6 10647 181 46675228
Prescription form tampering 23.70 18.75 8 10645 672 46674737
Miosis 23.20 18.75 16 10637 6641 46668768
Self-injurious ideation 23.00 18.75 11 10642 2289 46673120
Dizziness 22.77 18.75 144 10509 340270 46335139
Overdose 22.10 18.75 62 10591 101917 46573492
Polydipsia 22.05 18.75 12 10641 3267 46672142
Tachyphrenia 22.05 18.75 9 10644 1285 46674124
Vertigo 21.72 18.75 41 10612 52007 46623402
Drug screen false positive 21.71 18.75 8 10645 869 46674540
Soft tissue injury 21.43 18.75 8 10645 901 46674508
Hyperaldosteronism 21.38 18.75 6 10647 271 46675138
Muscle twitching 20.92 18.75 21 10632 14651 46660758
Hyponatraemia 20.40 18.75 60 10593 101272 46574137
Dyspnoea 20.25 18.75 56 10597 515492 46159917
Hyperhidrosis 20.04 18.75 55 10598 89253 46586156
Restless legs syndrome 19.58 18.75 21 10632 15822 46659587
Cor pulmonale acute 19.51 18.75 6 10647 374 46675035
Headache 18.93 18.75 179 10474 478173 46197236
Hypomania 18.81 18.75 12 10641 4376 46671033

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
Suicidal ideation 280.00 27.45 123 3943 35991 29912421
Completed suicide 148.27 27.45 116 3950 99376 29849036
Sexual dysfunction 93.82 27.45 34 4032 5967 29942445
Nausea 86.25 27.45 148 3918 296809 29651603
Anxiety 79.45 27.45 78 3988 89793 29858619
Intentional overdose 60.71 27.45 48 4018 41433 29906979
Suicide attempt 54.85 27.45 43 4023 36654 29911758
Dystonic tremor 54.06 27.45 10 4056 112 29948300
Depression 52.63 27.45 63 4003 90374 29858038
Feeling abnormal 45.89 27.45 47 4019 56709 29891703
Mania 42.52 27.45 22 4044 9132 29939280
Intentional self-injury 37.02 27.45 23 4043 13509 29934903
No adverse event 36.38 27.45 25 4041 17394 29931018
Vomiting 36.34 27.45 87 3979 219731 29728681
Abulia 35.24 27.45 9 4057 481 29947931
Agitation 31.94 27.45 38 4028 54035 29894377
Anger 30.67 27.45 19 4047 11101 29937311
Prescribed overdose 29.80 27.45 17 4049 8544 29939868
Anorgasmia 28.59 27.45 8 4058 607 29947805

Pharmacologic Action:

SourceCodeDescription
ATC N06AX26 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Other antidepressants
MeSH PA D014151 Anti-Anxiety Agents
MeSH PA D000928 Antidepressive Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D011619 Psychotropic Drugs
MeSH PA D058825 Serotonin 5-HT1 Receptor Agonists
MeSH PA D058831 Serotonin 5-HT3 Receptor Antagonists
MeSH PA D018490 Serotonin Agents
MeSH PA D012702 Serotonin Antagonists
MeSH PA D017366 Serotonin Receptor Agonists
MeSH PA D017367 Serotonin Uptake Inhibitors
MeSH PA D014149 Tranquilizing Agents
CHEBI has role CHEBI:35469 thymoanaleptics
CHEBI has role CHEBI:35474 minor tranquilisers
CHEBI has role CHEBI:35941 serotonergic agonists
CHEBI has role CHEBI:48279 serotonin antagonists

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Major depressive disorder indication 370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.02 Basic
pKa2 1.85 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 10MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL May 2, 2021 ADDITION TO THE CLINICAL STUDIES SECTION OF THE LABELING WITH THE SUBSECTION ENTITLED DIGIT SYMBOL SUBSTITUTION TEST IN MAJOR DEPRESSIVE DISORDER
EQ 15MG BASE **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 DISCN TABLET ORAL May 2, 2021 ADDITION TO THE CLINICAL STUDIES SECTION OF THE LABELING WITH THE SUBSECTION ENTITLED DIGIT SYMBOL SUBSTITUTION TEST IN MAJOR DEPRESSIVE DISORDER
EQ 20MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL May 2, 2021 ADDITION TO THE CLINICAL STUDIES SECTION OF THE LABELING WITH THE SUBSECTION ENTITLED DIGIT SYMBOL SUBSTITUTION TEST IN MAJOR DEPRESSIVE DISORDER
EQ 5MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL May 2, 2021 ADDITION TO THE CLINICAL STUDIES SECTION OF THE LABELING WITH THE SUBSECTION ENTITLED DIGIT SYMBOL SUBSTITUTION TEST IN MAJOR DEPRESSIVE DISORDER
EQ 10MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Oct. 19, 2021 UPDATE TO THE PRESCRIBING INFORMATION FOR VORTIOXETINE ON TREATMENT-EMERGENT SEXUAL DYSFUNCTION COMPARING VORTIOXETINE AND SSRIS
EQ 15MG BASE **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 DISCN TABLET ORAL Oct. 19, 2021 UPDATE TO THE PRESCRIBING INFORMATION FOR VORTIOXETINE ON TREATMENT-EMERGENT SEXUAL DYSFUNCTION COMPARING VORTIOXETINE AND SSRIS
EQ 20MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Oct. 19, 2021 UPDATE TO THE PRESCRIBING INFORMATION FOR VORTIOXETINE ON TREATMENT-EMERGENT SEXUAL DYSFUNCTION COMPARING VORTIOXETINE AND SSRIS
EQ 5MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Oct. 19, 2021 UPDATE TO THE PRESCRIBING INFORMATION FOR VORTIOXETINE ON TREATMENT-EMERGENT SEXUAL DYSFUNCTION COMPARING VORTIOXETINE AND SSRIS
EQ 10MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Nov. 13, 2023 INFORMATION ADDED TO THE LABELING REGARDING THE RESULT OF STUDY LUAA21004-402
EQ 15MG BASE **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 DISCN TABLET ORAL Nov. 13, 2023 INFORMATION ADDED TO THE LABELING REGARDING THE RESULT OF STUDY LUAA21004-402
EQ 20MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Nov. 13, 2023 INFORMATION ADDED TO THE LABELING REGARDING THE RESULT OF STUDY LUAA21004-402
EQ 5MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Nov. 13, 2023 INFORMATION ADDED TO THE LABELING REGARDING THE RESULT OF STUDY LUAA21004-402
EQ 10MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Jan. 22, 2024 ADDITION OF CLINICAL INFORMATION OBTAINED FROM A PEDIATRIC TRIAL TO SECTION 8.4 OF THE LABELING
EQ 15MG BASE **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 DISCN TABLET ORAL Jan. 22, 2024 ADDITION OF CLINICAL INFORMATION OBTAINED FROM A PEDIATRIC TRIAL TO SECTION 8.4 OF THE LABELING
EQ 20MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Jan. 22, 2024 ADDITION OF CLINICAL INFORMATION OBTAINED FROM A PEDIATRIC TRIAL TO SECTION 8.4 OF THE LABELING
EQ 5MG BASE TRINTELLIX TAKEDA PHARMS USA N204447 Sept. 30, 2013 RX TABLET ORAL Jan. 22, 2024 ADDITION OF CLINICAL INFORMATION OBTAINED FROM A PEDIATRIC TRIAL TO SECTION 8.4 OF THE LABELING

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
5-hydroxytryptamine receptor 1A GPCR AGONIST Ki 7.82 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter Transporter INHIBITOR Ki 8.80 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 7.72 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1D GPCR ANTAGONIST Ki 7.27 DRUG LABEL DRUG LABEL
5-hydroxytryptamine receptor 1B GPCR AGONIST Ki 7.48 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 3A Ion channel ANTAGONIST Ki 8.43 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Histamine H2 receptor GPCR Ki 6.74 CHEMBL
5-hydroxytryptamine receptor 2C GPCR Ki 6.74 CHEMBL
5-hydroxytryptamine receptor 2A GPCR Ki 6.74 CHEMBL
Histamine H1 receptor GPCR Ki 6.74 CHEMBL
5-hydroxytryptamine receptor 5A GPCR Ki 6.66 CHEMBL
5-hydroxytryptamine receptor 6 GPCR Ki 6.48 CHEMBL
Beta-2 adrenergic receptor GPCR Ki 6.25 CHEMBL
Beta-1 adrenergic receptor GPCR Ki 7.34 CHEMBL
Sodium-dependent serotonin transporter Transporter IC50 8.28 CHEMBL
5-hydroxytryptamine receptor 1D GPCR ANTAGONIST IC50 5.40 IUPHAR
5-hydroxytryptamine receptor 7 GPCR Ki 6.70 SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter Transporter IC50 6.05 CHEMBL
5-hydroxytryptamine receptor 3A Ion channel Ki 6.64 CHEMBL

External reference:

IDSource
D10184 KEGG_DRUG
1253056-29-9 SECONDARY_CAS_RN
4032784 VANDF
C3667599 UMLSCUI
CHEBI:76015 CHEBI
CHEMBL2104993 ChEMBL_ID
CHEMBL2107387 ChEMBL_ID
D000078784 MESH_DESCRIPTOR_UI
9966051 PUBCHEM_CID
9279 INN_ID
3O2K1S3WQV UNII
7351 IUPHAR_LIGAND_ID
DB09068 DRUGBANK_ID
1439824 RXNORM
206222 MMSL
235694 MMSL
29689 MMSL
d08125 MMSL
015226 NDDF
015227 NDDF
708717008 SNOMEDCT_US
712748004 SNOMEDCT_US
768282000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 55154-0256 TABLET, FILM COATED 10 mg ORAL NDA 30 sections
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 55154-0257 TABLET, FILM COATED 20 mg ORAL NDA 30 sections
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 64764-720 TABLET, FILM COATED 5 mg ORAL NDA 31 sections
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 64764-730 TABLET, FILM COATED 10 mg ORAL NDA 31 sections
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 64764-750 TABLET, FILM COATED 20 mg ORAL NDA 31 sections
Trintellix HUMAN PRESCRIPTION DRUG LABEL 1 70518-2642 TABLET, FILM COATED 20 mg ORAL NDA 29 sections