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

Stem definitionDrug idCAS RN
psychotropics, phenylpiperazine derivatives 5014 913611-97-9

Description:

MoleculeDescription

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:

DoseUnitRoute
3 mg O

ADMET properties:

PropertyValueReference
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:

DateAgencyCompanyOrphan
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 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
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 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
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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
Schizophrenia indication 58214004 DOID:5419
Major depressive disorder indication 370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.14 acidic
pKa2 8.07 Basic
pKa3 0.9 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
D(2) dopamine receptor GPCR AGONIST Ki 9.52 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 1A GPCR AGONIST Ki 9.92 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 2A GPCR ANTAGONIST Ki 9.33 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 2C GPCR Ki 7.47 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 5A GPCR Ki 6.85 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 6 GPCR Ki 7.24 SCIENTIFIC LITERATURE
Alpha-1A adrenergic receptor GPCR Ki 8.42 SCIENTIFIC LITERATURE
Alpha-2A adrenergic receptor GPCR Ki 7.82 SCIENTIFIC LITERATURE
Alpha-2B adrenergic receptor GPCR Ki 7.77 SCIENTIFIC LITERATURE
Beta-1 adrenergic receptor GPCR Ki 7.23 SCIENTIFIC LITERATURE
Beta-2 adrenergic receptor GPCR Ki 7.17 SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter Transporter INHIBITOR IC50 7.54 SCIENTIFIC LITERATURE
Sodium-dependent noradrenaline transporter Transporter INHIBITOR IC50 6.86 SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter Transporter INHIBITOR IC50 6.02 SCIENTIFIC LITERATURE
D(3) dopamine receptor GPCR AGONIST Ki 8.96 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 2B GPCR ANTAGONIST Ki 8.72 SCIENTIFIC LITERATURE
Alpha-1B adrenergic receptor GPCR ANTAGONIST Ki 9.77 SCIENTIFIC LITERATURE
Alpha-2C adrenergic receptor GPCR ANTAGONIST Ki 9.23 SCIENTIFIC LITERATURE
Histamine H1 receptor GPCR ANTAGONIST Ki 7.72 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 8.43 SCIENTIFIC LITERATURE
D(1A) dopamine receptor GPCR AGONIST Ki 6.80 SCIENTIFIC LITERATURE
Alpha-1D adrenergic receptor GPCR ANTAGONIST Ki 8.59 SCIENTIFIC LITERATURE
D(4) dopamine receptor GPCR AGONIST Ki 8.20 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1B GPCR Ki 7.49 SCIENTIFIC LITERATURE

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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