aprepitant indications/contra

Stem definitionDrug idCAS RN
neurokinin NK1 (substance P) receptor antagonist 230 170729-80-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • emend
  • aprepitant
  • L-754030
Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions.
  • Molecular weight: 534.44
  • Formula: C23H21F7N4O3
  • CLOGP: 4.60
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 2
  • TPSA: 75.19
  • ALOGS: -4.44
  • ROTB: 8

Drug dosage:

DoseUnitRoute
95 mg O
95 mg P

Approvals:

DateAgencyCompanyOrphan
March 27, 2003 FDA MERCK

FDA Adverse Event Reporting System

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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
Encephalopathy 361.23 42.92 91 1893 7371 3376504
Nausea 314.07 42.92 172 1812 129473 3254402
Diarrhoea 270.17 42.92 145 1839 104203 3279672
Alopecia 253.11 42.92 85 1899 18901 3364974
Fatigue 235.98 42.92 134 1850 107106 3276769
Vomiting 216.03 42.92 119 1865 89412 3294463
Constipation 212.94 42.92 85 1899 30727 3353148
Flushing 203.07 42.92 67 1917 14046 3369829
Decreased appetite 188.54 42.92 85 1899 41405 3342470
Oral pain 176.46 42.92 45 1939 3783 3380092
Erythema 163.16 42.92 69 1915 28741 3355134
Dyspnoea 152.06 42.92 100 1884 102834 3281041
Mouth ulceration 150.74 42.92 41 1943 4419 3379456
Pyrexia 147.65 42.92 90 1894 81025 3302850
Drug interaction 142.74 42.92 73 1911 46739 3337136
Hiccups 140.58 42.92 31 1953 1387 3382488
Change of bowel habit 128.48 42.92 23 1961 343 3383532
Asthenia 124.81 42.92 75 1909 65590 3318285
Neutropenia 122.18 42.92 59 1925 33327 3350548
Neuropathy peripheral 117.93 42.92 47 1937 16760 3367115
Febrile neutropenia 115.79 42.92 48 1936 18927 3364948
Hepatocellular injury 114.65 42.92 33 1951 4362 3379513
Paraesthesia 113.97 42.92 53 1931 27495 3356380
Mucosal inflammation 110.99 42.92 37 1947 7946 3375929
Abdominal pain 104.07 42.92 59 1925 46166 3337709
Pain in extremity 103.28 42.92 60 1924 49152 3334723
Emotional disorder 100.08 42.92 27 1957 2812 3381063
Cholestasis 99.83 42.92 31 1953 5306 3378569
Thrombocytopenia 95.83 42.92 51 1933 35217 3348658
Stoma site pain 94.98 42.92 14 1970 53 3383822

Pharmacologic Action:

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SourceCodeDescription
ATC A04AD12 ALIMENTARY TRACT AND METABOLISM
ANTIEMETICS AND ANTINAUSEANTS
ANTIEMETICS AND ANTINAUSEANTS
Other antiemetics
FDA MoA N0000010262 Neurokinin 1 Antagonists
FDA EPC N0000175786 Substance P/Neurokinin-1 Receptor Antagonist
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000185507 Cytochrome P450 2C9 Inducers
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
MeSH PA D000932 Antiemetics
MeSH PA D001337 Autonomic Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D064729 Neurokinin-1 Receptor Antagonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018373 Peripheral Nervous System Agents
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:50919 antiemetic
CHEBI has role CHEBI:49110 peripheral nervous system drug

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Chemotherapy-induced nausea and vomiting indication 236084000
Prevention of Post-Operative Nausea and Vomiting indication
Hepatic failure contraindication 59927004

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.8 acidic
pKa2 13.0 acidic
pKa3 3.22 Basic
pKa4 2.56 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
125MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 6096742 July 1, 2018 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
125MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 6096742 July 1, 2018 TREATMENT OR PREVENTION OF EMESIS
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL 6096742 July 1, 2018 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL 6096742 July 1, 2018 PREVENTION OF POST-OPERATIVE NAUSEA AND VOMITING
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL 6096742 July 1, 2018 TREATMENT OR PREVENTION OF EMESIS
80MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 6096742 July 1, 2018 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
80MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 6096742 July 1, 2018 TREATMENT OR PREVENTION OF EMESIS
125MG/KIT EMEND MSD MERCK CO N207865 Dec. 17, 2015 RX FOR SUSPENSION ORAL 6096742 July 1, 2018 PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY (CINV)
125MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 8258132 Sept. 26, 2027 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
125MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 8258132 Sept. 26, 2027 PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL 8258132 Sept. 26, 2027 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL 8258132 Sept. 26, 2027 PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
80MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 8258132 Sept. 26, 2027 FOR THE PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY
80MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL 8258132 Sept. 26, 2027 PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
125MG/KIT EMEND MSD MERCK CO N207865 Dec. 17, 2015 RX FOR SUSPENSION ORAL 8258132 Sept. 26, 2027 PREVENTION OF NAUSEA AND VOMITING ASSOCIATED WITH CHEMOTHERAPY (CINV)
130MG/18ML (7.2MG/ML) CINVANTI HERON THERAPS INC N209296 Nov. 9, 2017 RX EMULSION IV (INFUSION) 9561229 Sept. 18, 2035 TREATMENT OF NAUSEA AND VOMITING, INCLUDING THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY OR MODERATELY EMETOGENIC CANCER CHEMOTHERAPY
130MG/18ML (7.2MG/ML) CINVANTI HERON THERAPS INC N209296 Nov. 9, 2017 RX EMULSION IV (INFUSION) 9808465 Sept. 18, 2035 TREATMENT OF NAUSEA AND VOMITING, INCLUDING THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY OR MODERATELY EMETOGENIC CANCER CHEMOTHERAPY

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
125MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL Aug. 28, 2018 NEW PATIENT POPULATION
40MG EMEND MERCK N021549 June 30, 2006 RX CAPSULE ORAL Aug. 28, 2018 NEW PATIENT POPULATION
80MG EMEND MERCK N021549 March 26, 2003 RX CAPSULE ORAL Aug. 28, 2018 NEW PATIENT POPULATION
125MG/KIT EMEND MSD MERCK CO N207865 Dec. 17, 2015 RX FOR SUSPENSION ORAL Aug. 28, 2018 NEW PATIENT POPULATION

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Substance-P receptor GPCR ANTAGONIST Ki 10.70 CHEMBL CHEMBL
Cytochrome P450 3A4 Enzyme WOMBAT-PK
Neuromedin-K receptor GPCR Ki 6.34 CHEMBL
Substance-P receptor Unclassified IC50 10.05 CHEMBL

External reference:

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IDSource
3490 IUPHAR_LIGAND_ID
C1175300 UMLSCUI
D02968 KEGG_DRUG
1NF15YR6UY UNII
8050 INN_ID
DB00673 DRUGBANK_ID
d04855 MMSL
17180 MMSL
358255 RXNORM
398690007 SNOMEDCT_US
409205009 SNOMEDCT_US
4021391 VANDF
N0000148809 NDFRT
N0000010068 NDFRT
009926 NDDF
247683 MMSL
CHEMBL1471 ChEMBL_ID
6918365 PUBCHEM_CID
C114556 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:499361 CHEBI

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0461 CAPSULE 80 mg ORAL NDA 19 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0462 CAPSULE 125 mg ORAL NDA 19 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0464 CAPSULE 40 mg ORAL NDA 19 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-3066 POWDER, FOR SUSPENSION 125 mg ORAL NDA 19 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 2 0006-3862 KIT 80 mg None NDA 19 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 2 0006-3862 KIT 125 mg None NDA 19 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2321 CAPSULE 40 mg ORAL ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2322 CAPSULE 80 mg ORAL ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2323 CAPSULE 125 mg ORAL ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 2 0781-4063 KIT 125 mg None ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 2 0781-4063 KIT 80 mg None ANDA 17 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 42254-160 CAPSULE 40 mg ORAL NDA 17 sections
CINVANTI HUMAN PRESCRIPTION DRUG LABEL 1 47426-201 INJECTION, EMULSION 130 mg INTRAVENOUS NDA 17 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 54868-5231 CAPSULE 80 mg ORAL NDA 17 sections
Emend HUMAN PRESCRIPTION DRUG LABEL 2 54868-5325 KIT 80 mg None NDA 17 sections
Emend HUMAN PRESCRIPTION DRUG LABEL 2 54868-5325 KIT 125 mg None NDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 2 68462-112 KIT 80 mg None ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 2 68462-112 KIT 125 mg None ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-583 CAPSULE 40 mg ORAL ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-584 CAPSULE 80 mg ORAL ANDA 17 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-585 CAPSULE 125 mg ORAL ANDA 17 sections