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

Stem definitionDrug idCAS RN
neurokinin NK1 (substance P) receptor antagonist 4470 172673-20-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ivemend
  • fosaprepitant
  • fosaprepitant dimeglumine
  • fosaprepitant meglumine
a pro-drug form of aprepitant
  • Molecular weight: 614.41
  • Formula: C23H22F7N4O6P
  • CLOGP: 2.38
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 3
  • TPSA: 123.93
  • ALOGS: -4.99
  • ROTB: 9

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.07 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 18.60 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) 2.20 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 27, 2003 FDA

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
Erythema 346.84 39.97 115 1377 25044 2331549
Nausea 322.25 39.97 166 1326 112023 2244570
Flushing 311.06 39.97 89 1403 11782 2344811
Dyspnoea 267.43 39.97 131 1361 78602 2277991
Hypersensitivity 243.26 39.97 87 1405 23506 2333087
Encephalopathy 232.48 39.97 58 1434 4503 2352090
Hepatocellular injury 198.75 39.97 50 1442 4005 2352588
Hyponatraemia 136.26 39.97 49 1443 13276 2343317
Vomiting 121.81 39.97 76 1416 71526 2285067
Hypotension 111.95 39.97 55 1437 32381 2324212
Back pain 107.20 39.97 53 1439 31606 2324987
Diarrhoea 96.97 39.97 70 1422 83494 2273099
Chest discomfort 96.21 39.97 39 1453 14556 2342037
Sense of oppression 89.23 39.97 16 1476 241 2356352
Injection site phlebitis 86.69 39.97 13 1479 57 2356536
Malaise 84.27 39.97 55 1437 55530 2301063
Seizure 79.85 39.97 40 1452 24426 2332167
Infusion related reaction 77.89 39.97 30 1462 9766 2346827
Feeling hot 76.42 39.97 27 1465 6901 2349692
Rash 76.06 39.97 53 1439 59505 2297088
Abdominal pain 75.05 39.97 43 1449 34331 2322262
Drug interaction 73.22 39.97 40 1452 29123 2327470
Inappropriate antidiuretic hormone secretion 72.29 39.97 20 1472 2289 2354304
Pruritus 70.81 39.97 45 1447 43295 2313298
Infusion site pain 70.42 39.97 17 1475 1135 2355458
Febrile bone marrow aplasia 70.02 39.97 16 1476 841 2355752
Bone marrow failure 69.78 39.97 24 1468 5662 2350931
Injection site induration 67.83 39.97 20 1472 2874 2353719
Mucosal inflammation 67.82 39.97 23 1469 5201 2351392
Cough 63.22 39.97 38 1454 33079 2323514
Pyrexia 62.04 39.97 45 1447 53663 2302930
No adverse event 61.12 39.97 25 1467 9503 2347090
Dysphagia 60.34 39.97 27 1465 12778 2343815
Hepatitis 59.75 39.97 22 1470 6315 2350278
Paraesthesia 57.33 39.97 31 1461 22057 2334536
Rash erythematous 57.28 39.97 21 1471 5955 2350638
Anorectal disorder 56.00 39.97 11 1481 276 2356317
Anaphylactic reaction 53.96 39.97 23 1469 9682 2346911
Tremor 53.62 39.97 29 1463 20632 2335961
Injection site vasculitis 52.66 39.97 7 1485 9 2356584
Anaphylactic shock 52.21 39.97 18 1474 4268 2352325
Atelectasis 47.87 39.97 14 1478 1951 2354642
Oxygen saturation decreased 45.56 39.97 19 1473 7567 2349026
Infusion site streaking 45.01 39.97 6 1486 8 2356585
Feeling abnormal 44.78 39.97 27 1465 23554 2333039
Constipation 44.29 39.97 26 1466 21603 2334990
Urticaria 44.07 39.97 27 1465 24234 2332359
Thrombocytopenic purpura 42.47 39.97 9 1483 332 2356261
Tachycardia 42.45 39.97 23 1469 16386 2340207
Computerised tomogram thorax abnormal 42.31 39.97 8 1484 163 2356430
Product quality issue 42.12 39.97 20 1472 10809 2345784
Hypophagia 41.83 39.97 15 1477 3985 2352608
Neutropenia 41.75 39.97 25 1467 21523 2335070
Confusional state 41.44 39.97 26 1466 24318 2332275
Headache 40.70 39.97 42 1450 80137 2276456
Acute kidney injury 40.41 39.97 27 1465 28095 2328498
Throat tightness 40.32 39.97 15 1477 4421 2352172

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
Erythema 336.48 48.30 100 889 14088 1731704
Hypersensitivity 218.06 48.30 67 922 10377 1735415
Thrombocytopenia 143.46 48.30 59 930 21190 1724602
Encephalopathy 129.32 48.30 37 952 4415 1741377
Dyspnoea 116.83 48.30 68 921 51991 1693801
Flushing 112.62 48.30 36 953 6243 1739549
Jaundice 105.59 48.30 34 955 6028 1739764
Hiccups 104.86 48.30 25 964 1452 1744340
Acute kidney injury 103.77 48.30 55 934 34889 1710903
Hypotension 103.35 48.30 52 937 29602 1716190
Chest discomfort 103.18 48.30 35 954 7296 1738496
Hepatocellular injury 98.89 48.30 28 961 3203 1742589
Nausea 81.78 48.30 54 935 51142 1694650
Oxygen saturation decreased 79.39 48.30 27 962 5648 1740144
Cholestasis 78.08 48.30 24 965 3641 1742151
Fixed eruption 76.09 48.30 14 975 223 1745569
Platelet count increased 72.70 48.30 19 970 1602 1744190
Vomiting 69.87 48.30 44 945 38271 1707521
Malaise 66.85 48.30 39 950 29526 1716266
Leukopenia 65.30 48.30 26 963 8454 1737338
Diarrhoea 65.25 48.30 48 941 53804 1691988
Testicular germ cell cancer metastatic 60.53 48.30 8 981 8 1745784
Haemolysis 58.89 48.30 15 974 1140 1744652
Pruritus 58.77 48.30 33 956 23189 1722603
Transaminases increased 56.16 48.30 19 970 3898 1741894
Pyrexia 55.30 48.30 41 948 46359 1699433
Neutropenia 49.01 48.30 27 962 18233 1727559
Back pain 48.57 48.30 26 963 16587 1729205

Pharmacologic Action:

SourceCodeDescription
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
CHEBI has role CHEBI:50919 antiemetic
CHEBI has role CHEBI:50266 prodrug

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chemotherapy-induced nausea and vomiting indication 236084000
Hepatic failure contraindication 59927004

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 0.87 acidic
pKa2 6.2 acidic
pKa3 8.25 acidic
pKa4 10.36 acidic
pKa5 3.99 Basic
pKa6 1.47 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 115MG BASE/VIAL **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** EMEND MERCK AND CO INC N022023 Jan. 25, 2008 DISCN POWDER INTRAVENOUS April 3, 2021 NEW PATIENT POPULATION
EQ 150MG BASE/VIAL EMEND MERCK AND CO INC N022023 Nov. 12, 2010 RX POWDER INTRAVENOUS April 3, 2021 NEW PATIENT POPULATION
EQ 115MG BASE/VIAL **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** EMEND MERCK AND CO INC N022023 Jan. 25, 2008 DISCN POWDER INTRAVENOUS Oct. 3, 2021 PEDIATRIC EXCLUSIVITY
EQ 150MG BASE/VIAL EMEND MERCK AND CO INC N022023 Nov. 12, 2010 RX POWDER INTRAVENOUS Oct. 3, 2021 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Substance-P receptor GPCR ANTAGONIST IC50 8.92 IUPHAR CHEMBL

External reference:

IDSource
D06597 KEGG_DRUG
4027247 VUID
N0000176136 NUI
C2315887 UMLSCUI
6L8OF9XRDC UNII
8699 INN_ID
265121-04-8 SECONDARY_CAS_RN
C579707 MESH_SUPPLEMENTAL_RECORD_UI
CHEMBL1199324 ChEMBL_ID
DB06717 DRUGBANK_ID
CHEBI:64321 CHEBI
CHEMBL1201782 ChEMBL_ID
135413538 PUBCHEM_CID
7623 IUPHAR_LIGAND_ID
429822007 SNOMEDCT_US
322336 MMSL
d07080 MMSL
4027246 VANDF
429825009 SNOMEDCT_US
012534 NDDF
1731071 RXNORM
DB00673 DRUGBANK_ID

Pharmaceutical products:

None