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

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

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
165 mg O
150 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.34 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 62.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.94 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 13 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 27, 2003 FDA MERCK

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
Febrile neutropenia 354.49 17.15 288 17073 94339 46574362
Nausea 209.20 17.15 642 16719 686812 45981889
Erythema 161.13 17.15 230 17131 142590 46526111
Mucosal inflammation 159.17 17.15 125 17236 38851 46629850
Neutropenia 157.72 17.15 228 17133 142976 46525725
Encephalopathy 148.66 17.15 113 17248 33476 46635225
Drug ineffective 101.36 17.15 64 17297 677774 45990927
Febrile bone marrow aplasia 95.46 17.15 48 17313 6814 46661887
Flushing 94.08 17.15 118 17243 64496 46604205
Atelectasis 87.05 17.15 65 17296 18725 46649976
Computerised tomogram thorax abnormal 84.90 17.15 28 17333 1333 46667368
Pyrexia 80.41 17.15 298 17063 348504 46320197
Hypoxia 66.56 17.15 89 17272 51749 46616952
Hepatocellular injury 61.66 17.15 65 17296 29457 46639244
Vomiting 61.19 17.15 330 17031 452464 46216237
Hyponatraemia 60.40 17.15 123 17238 101209 46567492
Bone marrow failure 59.63 17.15 64 17297 29605 46639096
Decreased appetite 59.00 17.15 182 17179 193654 46475047
Palmar-plantar erythrodysaesthesia syndrome 55.63 17.15 52 17309 20399 46648302
Vascular pain 55.10 17.15 17 17344 651 46668050
Dyspnoea 54.97 17.15 353 17008 515195 46153506
Infusion site streaking 51.51 17.15 14 17347 339 46668362
Diarrhoea 50.63 17.15 368 16993 559234 46109467
Constipation 49.77 17.15 160 17201 173937 46494764
Neutrophil count decreased 48.90 17.15 70 17291 43356 46625345
Sense of oppression 47.73 17.15 17 17344 1022 46667679
Fall 46.36 17.15 33 17328 329064 46339637
Aplasia 43.90 17.15 23 17338 3553 46665148
Respiratory syncytial virus infection 42.62 17.15 25 17336 4810 46663891
Inappropriate antidiuretic hormone secretion 42.53 17.15 38 17323 14064 46654637
Gastrointestinal disorder 41.17 17.15 77 17284 59499 46609202
Hypersensitivity 39.23 17.15 134 17227 150187 46518514
Alveolitis 39.18 17.15 19 17342 2494 46666207
Oral pain 38.81 17.15 47 17314 24750 46643951
Chemotherapy 36.44 17.15 15 17346 1337 46667364
Anaphylactic shock 36.00 17.15 41 17320 20233 46648468
Tonsillar haemorrhage 34.20 17.15 9 17352 192 46668509
Cerebellar syndrome 33.43 17.15 19 17342 3446 46665255
Abdominal pain 33.20 17.15 171 17190 229860 46438841
Interstitial lung disease 32.72 17.15 66 17295 53883 46614818
Feeling hot 32.65 17.15 54 17307 37874 46630827
Chest discomfort 32.42 17.15 90 17271 90179 46578522
Neuropathy peripheral 32.03 17.15 90 17271 90803 46577898
Intestinal strangulation 29.99 17.15 7 17354 89 46668612
Depression 29.76 17.15 13 17348 170091 46498610
Joint swelling 28.57 17.15 13 17348 166060 46502641
Hypomagnesaemia 28.28 17.15 38 17323 22172 46646529
Drug intolerance 27.75 17.15 10 17351 147039 46521662
Injection site pain 26.69 17.15 4 17357 107148 46561553
Weight increased 26.58 17.15 14 17347 164459 46504242
Toxicity to various agents 26.32 17.15 24 17337 211742 46456959
Anorectal disorder 26.14 17.15 12 17349 1392 46667309
Colony stimulating factor therapy 25.79 17.15 8 17353 312 46668389
Intercepted product administration error 25.65 17.15 6 17355 77 46668624
Sputum abnormal 24.77 17.15 8 17353 356 46668345
Oropharyngeal discomfort 24.45 17.15 15 17346 3130 46665571
Gastrointestinal scarring 24.17 17.15 7 17354 215 46668486
Thrombocytopenic purpura 24.12 17.15 11 17350 1257 46667444
Leukopenia 23.41 17.15 67 17294 68276 46600425
Hypokalaemia 23.40 17.15 79 17282 87945 46580756
Gait disturbance 22.55 17.15 13 17348 145250 46523451
Periorbital cellulitis 22.28 17.15 8 17353 492 46668209
Laryngeal discomfort 22.20 17.15 7 17354 288 46668413
Antinuclear antibody 22.14 17.15 8 17353 501 46668200
Pain 22.01 17.15 97 17264 476851 46191850
Body temperature abnormal 21.88 17.15 10 17351 1148 46667553
Dysgeusia 21.59 17.15 47 17314 40444 46628257
Myocardial infarction 21.39 17.15 5 17356 97523 46571178
Tumour pain 21.32 17.15 10 17351 1219 46667482
Anaphylactic reaction 21.12 17.15 55 17306 53057 46615644
Hypermagnesaemia 20.75 17.15 9 17352 913 46667788
Infusion site vesicles 20.57 17.15 7 17354 367 46668334
Subacute cutaneous lupus erythematosus 19.83 17.15 11 17350 1904 46666797
Phlebitis 19.70 17.15 17 17344 6009 46662692
Hallucination, tactile 19.57 17.15 6 17355 225 46668476
Administration site oedema 18.93 17.15 4 17357 31 46668670
Paraesthesia 18.81 17.15 90 17271 117347 46551354
Bronchitis 18.68 17.15 8 17353 105971 46562730
Abdominal operation 18.68 17.15 7 17354 486 46668215
Dehydration 18.58 17.15 112 17249 159428 46509273
Toxic encephalopathy 18.02 17.15 15 17346 5047 46663654
White blood cell count decreased 17.97 17.15 86 17275 112145 46556556
Hypophagia 17.93 17.15 36 17325 29270 46639431
Musculoskeletal stiffness 17.92 17.15 7 17354 97986 46570715
Exposure during pregnancy 17.79 17.15 9 17352 108203 46560498

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
Febrile neutropenia 156.35 18.90 196 11050 106497 29834735
Hiccups 105.03 18.90 57 11189 9377 29931855
Erythema 91.21 18.90 128 11118 77323 29863909
Nausea 86.89 18.90 276 10970 296681 29644551
Neutropenia 81.80 18.90 161 11085 128379 29812853
Hypersensitivity 80.10 18.90 100 11146 53928 29887304
Neutrophil count decreased 71.75 18.90 84 11162 42370 29898862
Drug ineffective 64.15 18.90 24 11222 340363 29600869
Vomiting 60.18 18.90 200 11046 219618 29721614
Thrombocytopenia 57.07 18.90 145 11101 136899 29804333
Fixed eruption 52.81 18.90 19 11227 1165 29940067
Intestinal ischaemia 51.08 18.90 32 11214 6865 29934367
Decreased appetite 50.77 18.90 147 11099 149763 29791469
Diarrhoea 47.85 18.90 249 10997 333854 29607378
Encephalopathy 46.71 18.90 59 11187 32146 29909086
Hepatocellular injury 45.70 18.90 52 11194 25419 29915813
Mouth ulceration 42.93 18.90 34 11212 10575 29930657
Stomatitis 42.89 18.90 61 11185 37218 29904014
Testicular germ cell cancer metastatic 42.58 18.90 9 11237 69 29941163
Aplasia 41.09 18.90 23 11223 4014 29937218
Toxicity to various agents 37.72 18.90 10 11236 177173 29764059
Sense of oppression 34.53 18.90 11 11235 464 29940768
Stoma site pain 33.83 18.90 12 11234 706 29940526
Emotional disorder 33.67 18.90 22 11224 5072 29936160
Change of bowel habit 33.25 18.90 13 11233 1004 29940228
Toxic encephalopathy 33.17 18.90 21 11225 4588 29936644
Seminoma 32.53 18.90 9 11237 231 29941001
Mucosal inflammation 32.31 18.90 48 11198 30446 29910786
Oral pain 31.32 18.90 27 11219 9442 29931790
Neuropathy peripheral 30.76 18.90 76 11170 70399 29870833
Febrile bone marrow aplasia 30.74 18.90 25 11221 8072 29933160
Alopecia 30.65 18.90 37 11209 19238 29921994
Bone marrow failure 30.29 18.90 46 11200 29739 29911493
White blood cell count decreased 29.98 18.90 84 11162 83863 29857369
Paraesthesia 28.53 18.90 63 11183 54264 29886968
Flushing 27.83 18.90 44 11202 29448 29911784
Anaphylactic shock 27.55 18.90 30 11216 13963 29927269
Leukopenia 27.12 18.90 63 11183 56096 29885136
Enteritis 26.25 18.90 21 11225 6624 29934608
Large intestine perforation 25.68 18.90 22 11224 7629 29933603
Anaphylactic reaction 25.37 18.90 41 11205 27941 29913291
Platelet count increased 25.08 18.90 23 11223 8719 29932513
Septic shock 25.05 18.90 66 11180 63541 29877691
Dehydration 24.90 18.90 102 11144 123437 29817795
Interstitial lung disease 24.26 18.90 63 11183 60134 29881098
Chemotherapeutic drug level increased 23.95 18.90 7 11239 220 29941012
Jaundice 23.42 18.90 43 11203 32443 29908789
Constipation 23.37 18.90 94 11152 112812 29828420
Acute kidney injury 23.32 18.90 179 11067 273663 29667569
Platelet count decreased 23.29 18.90 90 11156 106039 29835193
Pyrexia 22.63 18.90 188 11058 294301 29646931
Incorrect drug administration rate 21.98 18.90 10 11236 1126 29940106
Peritonitis 21.71 18.90 33 11213 21342 29919890
Hyperammonaemic encephalopathy 20.12 18.90 11 11235 1833 29939399
Necrotising ulcerative gingivostomatitis 19.80 18.90 5 11241 89 29941143
Cardiac failure congestive 19.45 18.90 4 11242 84403 29856829

Pharmacologic Action:

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
MeSH PA D000932 Antiemetics
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
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000185507 Cytochrome P450 2C9 Inducers
CHEBI has role CHEBI:35469 thymoanaleptics
CHEBI has role CHEBI:49110 peripheral nervous system agent
CHEBI has role CHEBI:50919 antiemetico
CHEBI has role CHEBI:55350 neurokinin-1 receptor antagonists
CHEBI has role CHEBI:55351 substance p receptor antagonists

Drug Use (View source of the data)

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

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)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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:

IDSource
1NF15YR6UY UNII
D02968 KEGG_DRUG
C1176306 UMLSCUI
CHEBI:499361 CHEBI
CHEMBL1471 ChEMBL_ID
CHEMBL1201782 ChEMBL_ID
DB00673 DRUGBANK_ID
D000077608 MESH_DESCRIPTOR_UI
135413536 PUBCHEM_CID
8050 INN_ID
3490 IUPHAR_LIGAND_ID
357280 RXNORM
17180 MMSL
247683 MMSL
46392 MMSL
d04855 MMSL
009926 NDDF
398690007 SNOMEDCT_US
409205009 SNOMEDCT_US
4021391 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0461 CAPSULE 80 mg ORAL NDA 31 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0462 CAPSULE 125 mg ORAL NDA 31 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-0464 CAPSULE 40 mg ORAL NDA 31 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 0006-3066 POWDER, FOR SUSPENSION 125 mg ORAL NDA 31 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2321 CAPSULE 40 mg ORAL ANDA 26 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2322 CAPSULE 80 mg ORAL ANDA 26 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 0781-2323 CAPSULE 125 mg ORAL ANDA 26 sections
APREPITANT HUMAN PRESCRIPTION DRUG LABEL 1 13668-591 CAPSULE 40 mg ORAL ANDA 24 sections
APREPITANT HUMAN PRESCRIPTION DRUG LABEL 1 13668-592 CAPSULE 80 mg ORAL ANDA 24 sections
APREPITANT HUMAN PRESCRIPTION DRUG LABEL 1 13668-593 CAPSULE 125 mg ORAL ANDA 24 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 42254-160 CAPSULE 40 mg ORAL NDA 26 sections
CINVANTI HUMAN PRESCRIPTION DRUG LABEL 1 47426-201 INJECTION, EMULSION 130 mg INTRAVENOUS NDA 28 sections
EMEND HUMAN PRESCRIPTION DRUG LABEL 1 54868-5231 CAPSULE 80 mg ORAL NDA 26 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-583 CAPSULE 40 mg ORAL ANDA 25 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-584 CAPSULE 80 mg ORAL ANDA 25 sections
Aprepitant HUMAN PRESCRIPTION DRUG LABEL 1 68462-585 CAPSULE 125 mg ORAL ANDA 25 sections