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

Stem definition	Drug id	CAS RN
psychotropics, phenylpiperazine derivatives	5014	913611-97-9

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: brexpiprazole rexulti OPC-34712 OPC 34712

an atypical antipsychotic the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors Molecular weight: 433.57 Formula: C25H27N3O2S CLOGP: 4.65 LIPINSKI: 0 HAC: 5 HDO: 1 TPSA: 44.81 ALOGS: -5.28 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

Dose	Unit	Route
3	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
Vd (Volume of distribution)	1.46 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.34 mL/min/kg	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	54.37 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 27, 2018	EMA	OTSUKA PHARM CO LTD
Jan. 19, 2018	PMDA	Otsuka Pharmaceutical Co., Ltd.
July 10, 2015	FDA	OTSUKA PHARM CO LTD

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
Weight increased	581.61	35.87	158	1053	22179	2334695
Off label use	559.02	35.87	202	1009	73396	2283478
Akathisia	523.90	35.87	92	1119	1582	2355292
Restlessness	173.34	35.87	44	1167	4519	2352355
Tardive dyskinesia	130.45	35.87	29	1182	1675	2355199
Mania	114.96	35.87	28	1183	2412	2354462
Inability to afford medication	106.58	35.87	18	1193	235	2356639
Product use in unapproved indication	106.52	35.87	37	1174	11163	2345711
Anxiety	102.48	35.87	47	1164	29312	2327562
Product administered to patient of inappropriate age	97.96	35.87	20	1191	764	2356110
Insomnia	89.04	35.87	41	1170	25746	2331128
Suicidal ideation	87.84	35.87	32	1179	11055	2345819
Tremor	81.27	35.87	36	1175	20625	2336249
Depression	79.57	35.87	39	1172	28093	2328781
Feeling abnormal	73.63	35.87	35	1176	23546	2333328
Wrong technique in product usage process	73.14	35.87	33	1178	19715	2337159
Anger	70.11	35.87	19	1192	2488	2354386
Adverse event	63.94	35.87	23	1188	7636	2349238
Extrapyramidal disorder	61.96	35.87	17	1194	2330	2354544
Increased appetite	55.09	35.87	14	1197	1426	2355448
Rash	52.47	35.87	39	1172	59519	2297355
Drug ineffective	50.98	35.87	48	1163	101576	2255298
Incorrect dose administered	48.28	35.87	20	1191	9675	2347199
Food craving	45.92	35.87	9	1202	277	2356597
Agitation	45.76	35.87	20	1191	11031	2345843
Product use issue	43.91	35.87	20	1191	12149	2344725
Crying	43.53	35.87	15	1196	4381	2352493
Hunger	43.01	35.87	10	1201	701	2356173
Product dose omission	42.75	35.87	29	1182	38228	2318646
Sedation	39.31	35.87	13	1198	3349	2353525
Eye movement disorder	38.43	35.87	10	1201	1117	2355757
Hypomania	36.63	35.87	9	1202	798	2356076

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
Off label use	262.76	48.98	91	465	38480	1707745
Akathisia	253.57	48.98	46	510	1282	1744943
Weight increased	142.22	48.98	43	513	11314	1734911
Anxiety	93.89	48.98	34	522	15493	1730732
Product administered to patient of inappropriate age	84.54	48.98	17	539	803	1745422
Restlessness	78.78	48.98	22	534	4299	1741926
No adverse event	70.45	48.98	21	535	5161	1741064
Suicidal ideation	56.34	48.98	20	536	8498	1737727
Product use in unapproved indication	50.69	48.98	19	537	9403	1736822

Pharmacologic Action:

Source	Code	Description
ATC	N05AX16	NERVOUS SYSTEM PSYCHOLEPTICS ANTIPSYCHOTICS Other antipsychotics
MeSH PA	D015259	Dopamine Agents
MeSH PA	D018491	Dopamine Agonists
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D018490	Serotonin Agents
FDA EPC	N0000175430	Atypical Antipsychotic

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Schizophrenia	indication	58214004	DOID:5419
Major depressive disorder	indication	370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.14	acidic
pKa2	8.07	Basic
pKa3	0.9	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
0.25MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
0.25MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
0.25MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
0.25MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
0.5MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
0.5MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
0.5MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
0.5MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
1MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
1MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
1MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
1MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
2MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
2MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
2MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
2MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
3MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
3MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
3MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
3MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
4MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8349840	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
4MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	8618109	April 12, 2026	TREATMENT OF SCHIZOPHRENIA
4MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	ADJUNCTIVE TREATMENT OF MAJOR DEPRESSIVE DISORDER (MDD)
4MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	9839637	April 12, 2026	TREATMENT OF SCHIZOPHRENIA

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
0.25MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY
0.5MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY
1MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY
2MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY
3MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY
4MG	REXULTI	OTSUKA PHARM CO LTD	N205422	July 10, 2015	RX	TABLET	ORAL	July 10, 2020	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
D(2) dopamine receptor	GPCR	P14416	DRD2_HUMAN	AGONIST	Ki	9.52		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN	AGONIST	Ki	9.92		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN	ANTAGONIST	Ki	9.33		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	7.47		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 5A	GPCR	P47898	5HT5A_HUMAN		Ki	6.85		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	7.24		SCIENTIFIC LITERATURE
Alpha-1A adrenergic receptor	GPCR	P35348	ADA1A_HUMAN		Ki	8.42		SCIENTIFIC LITERATURE
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	7.82		SCIENTIFIC LITERATURE
Alpha-2B adrenergic receptor	GPCR	P18089	ADA2B_HUMAN		Ki	7.77		SCIENTIFIC LITERATURE
Beta-1 adrenergic receptor	GPCR	P08588	ADRB1_HUMAN		Ki	7.23		SCIENTIFIC LITERATURE
Beta-2 adrenergic receptor	GPCR	P07550	ADRB2_HUMAN		Ki	7.17		SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN	INHIBITOR	IC50	7.54		SCIENTIFIC LITERATURE
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN	INHIBITOR	IC50	6.86		SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN	INHIBITOR	IC50	6.02		SCIENTIFIC LITERATURE
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN	AGONIST	Ki	8.96		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN	ANTAGONIST	Ki	8.72		SCIENTIFIC LITERATURE
Alpha-1B adrenergic receptor	GPCR	P35368	ADA1B_HUMAN	ANTAGONIST	Ki	9.77		SCIENTIFIC LITERATURE
Alpha-2C adrenergic receptor	GPCR	P18825	ADA2C_HUMAN	ANTAGONIST	Ki	9.23		SCIENTIFIC LITERATURE
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN	ANTAGONIST	Ki	7.72		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN	ANTAGONIST	Ki	8.43		SCIENTIFIC LITERATURE
D(1A) dopamine receptor	GPCR	P21728	DRD1_HUMAN	AGONIST	Ki	6.80		SCIENTIFIC LITERATURE
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN	ANTAGONIST	Ki	8.59		SCIENTIFIC LITERATURE
D(4) dopamine receptor	GPCR	P21917	DRD4_HUMAN	AGONIST	Ki	8.20		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN		Ki	7.49		SCIENTIFIC LITERATURE

External reference:

ID	Source
D10309	KEGG_DRUG
4034625	VUID
N0000191737	NUI
C3885614	UMLSCUI
2J3YBM1K8C	UNII
9552	INN_ID
781292006	SNOMEDCT_US
1658314	RXNORM
016270	NDDF
4034625	VANDF
d08373	MMSL
716069007	SNOMEDCT_US
31120	MMSL
11978813	PUBCHEM_CID
CHEBI:134716	CHEBI
DB09128	DRUGBANK_ID
7672	IUPHAR_LIGAND_ID
CHEMBL2105760	ChEMBL_ID
C000591922	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-035	TABLET	0.25 mg	ORAL	NDA	21 sections
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-036	TABLET	0.50 mg	ORAL	NDA	21 sections
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-037	TABLET	1 mg	ORAL	NDA	21 sections
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-038	TABLET	2 mg	ORAL	NDA	21 sections
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-039	TABLET	3 mg	ORAL	NDA	21 sections
REXULTI	HUMAN PRESCRIPTION DRUG LABEL	1	59148-040	TABLET	4 mg	ORAL	NDA	21 sections