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

Stem definition	Drug id	CAS RN
serotonin and/or norepinephrine reuptake inhibitors, fluoxetine derivatives	4806	508233-74-7

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
10	mg	O

ADMET properties:

Property	Value	Reference
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:

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

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
Major depressive disorder	indication	370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN	AGONIST	Ki	7.82	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN	INHIBITOR	Ki	8.80	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN	ANTAGONIST	Ki	7.72	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1D	GPCR	P28221	5HT1D_HUMAN	ANTAGONIST	Ki	7.27	DRUG LABEL	DRUG LABEL
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN	AGONIST	Ki	7.48	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 3A	Ion channel	P46098	5HT3A_HUMAN	ANTAGONIST	Ki	8.43	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Histamine H2 receptor	GPCR	P25021	HRH2_HUMAN		Ki	6.74	CHEMBL
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	6.74	CHEMBL
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN		Ki	6.74	CHEMBL
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN		Ki	6.74	CHEMBL
5-hydroxytryptamine receptor 5A	GPCR	P47898	5HT5A_HUMAN		Ki	6.66	CHEMBL
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	6.48	CHEMBL
Beta-2 adrenergic receptor	GPCR	P07550	ADRB2_HUMAN		Ki	6.25	CHEMBL
Beta-1 adrenergic receptor	GPCR	P08588	ADRB1_HUMAN		Ki	7.34	CHEMBL
Sodium-dependent serotonin transporter	Transporter		SC6A4_RAT		IC50	8.28	CHEMBL
5-hydroxytryptamine receptor 1D	GPCR		5HT1D_RAT	ANTAGONIST	IC50	5.40	IUPHAR
5-hydroxytryptamine receptor 7	GPCR		5HT7R_RAT		Ki	6.70	SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter	Transporter		SC6A3_RAT		IC50	6.05	CHEMBL
5-hydroxytryptamine receptor 3A	Ion channel		5HT3A_RAT		Ki	6.64	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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