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

Stem definitionDrug idCAS RN
serotonin receptor antagonists (5-HT3) 1329 109889-09-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • granisetron monohydrochloride
  • BRL-43694
  • granisetron
  • sancuso
  • kevatril
  • granisetron hydrochloride
  • granisetron HCl
A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.
  • Molecular weight: 312.42
  • Formula: C18H24N4O
  • CLOGP: 1.72
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 50.16
  • ALOGS: -2.86
  • ROTB: 2

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
2 mg O
3 mg P
3.10 mg TD

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 100 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 11 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.03 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 60 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 3.70 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 9.10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.35 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 5.20 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 29, 1993 FDA ROCHE

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 392.94 17.20 308 17344 94319 46574091
Neutropenia 183.08 17.20 247 17405 142957 46525453
Neutrophil count decreased 155.77 17.20 130 17522 43296 46625114
Nausea 155.04 17.20 588 17064 686866 45981544
Drug ineffective 153.01 17.20 35 17617 677803 45990607
Pyrexia 121.90 17.20 347 17305 348455 46319955
General physical health deterioration 111.78 17.20 175 17477 115594 46552816
Vomiting 106.19 17.20 393 17259 452401 46216009
Death 103.05 17.20 319 17333 335229 46333181
Leukopenia 99.75 17.20 126 17526 68217 46600193
Platelet count decreased 86.67 17.20 144 17508 99880 46568530
White blood cell count decreased 77.14 17.20 146 17506 112085 46556325
Decreased appetite 67.58 17.20 193 17459 193643 46474767
Stomatitis 65.49 17.20 103 17549 68194 46600216
Constipation 58.39 17.20 171 17481 173926 46494484
Disease progression 54.51 17.20 112 17540 91188 46577222
Diarrhoea 53.13 17.20 377 17275 559225 46109185
Polyneuropathy 52.71 17.20 40 17612 11604 46656806
Anaemia 52.28 17.20 213 17439 255566 46412844
Tooth erosion 47.05 17.20 14 17638 465 46667945
Thrombocytopenia 45.96 17.20 128 17524 126453 46541957
Pancytopenia 45.74 17.20 100 17552 84958 46583452
Joint swelling 45.24 17.20 5 17647 166068 46502342
Completed suicide 43.51 17.20 3 17649 145917 46522493
Drug hypersensitivity 43.33 17.20 19 17633 243806 46424604
Malignant neoplasm progression 41.54 17.20 82 17570 64844 46603566
Product dose omission issue 39.21 17.20 8 17644 168512 46499898
Mucosal inflammation 37.64 17.20 59 17593 38917 46629493
Fall 37.01 17.20 42 17610 329055 46339355
Toxicity to various agents 36.84 17.20 17 17635 211749 46456661
Dyspnoea 36.55 17.20 325 17327 515223 46153187
Condition aggravated 36.37 17.20 24 17628 245028 46423382
Pulpitis dental 36.24 17.20 13 17639 784 46667626
Bone marrow failure 34.50 17.20 49 17603 29620 46638790
Ileus 34.42 17.20 34 17618 14030 46654380
Palmar-plantar erythrodysaesthesia syndrome 31.87 17.20 39 17613 20412 46647998
Cytomegalovirus test positive 31.15 17.20 17 17635 2803 46665607
Weight increased 30.52 17.20 12 17640 164461 46503949
Periodontitis 30.43 17.20 18 17634 3458 46664952
Respiratory depth decreased 29.35 17.20 6 17646 38 46668372
Metastases to liver 28.36 17.20 36 17616 19549 46648861
Breast cancer metastatic 27.93 17.20 30 17622 13648 46654762
Erythema 27.58 17.20 117 17535 142703 46525707
Lymphoedema 27.21 17.20 24 17628 8588 46659822
Drug intolerance 26.83 17.20 11 17641 147038 46521372
Acute myeloid leukaemia recurrent 26.02 17.20 12 17640 1384 46667026
Venous thrombosis limb 25.52 17.20 15 17637 2848 46665562
Sepsis 25.16 17.20 110 17542 135904 46532506
Flushing 25.08 17.20 67 17585 64547 46603863
Lymphocyte count decreased 25.07 17.20 39 17613 25550 46642860
Acute graft versus host disease in skin 24.95 17.20 15 17637 2967 46665443
Off label use 23.59 17.20 233 17419 379608 46288802
Abdominal pain 23.44 17.20 158 17494 229873 46438537
Chronic hepatitis B 23.09 17.20 7 17645 248 46668162
Interstitial lung disease 23.05 17.20 58 17594 53891 46614519
Neuropathy peripheral 22.88 17.20 81 17571 90812 46577598
Hepatic function abnormal 22.64 17.20 44 17608 34377 46634033
Treatment failure 22.53 17.20 4 17648 93083 46575327
Subileus 22.31 17.20 14 17638 2989 46665421
Arthropathy 21.95 17.20 3 17649 84697 46583713
Arthralgia 21.94 17.20 68 17584 364535 46303875
Bone pain 21.72 17.20 52 17600 46838 46621572
Disseminated intravascular coagulation 21.52 17.20 31 17621 18974 46649436
Mitral valve disease 20.80 17.20 12 17640 2200 46666210
Mucosal dryness 20.42 17.20 12 17640 2278 46666132
Musculoskeletal stiffness 20.16 17.20 6 17646 97987 46570423
Hypokalaemia 20.09 17.20 76 17576 87948 46580462
Anaphylactic shock 20.00 17.20 31 17621 20243 46648167
Chest discomfort 19.83 17.20 77 17575 90192 46578218
Maternal exposure during pregnancy 19.82 17.20 7 17645 102542 46565868
Mucosal disorder 19.72 17.20 11 17641 1893 46666517
Therapeutic product effect incomplete 19.71 17.20 3 17649 78150 46590260
Acute interstitial pneumonitis 19.65 17.20 8 17644 682 46667728
Cytopenia 19.42 17.20 19 17633 7749 46660661
Pseudomembranous colitis 19.10 17.20 13 17639 3182 46665228
Peripheral swelling 19.04 17.20 19 17633 158052 46510358
Sinusitis 18.84 17.20 13 17639 129755 46538655
Tumour lysis syndrome 18.65 17.20 18 17634 7218 46661192
Pleural effusion 18.42 17.20 71 17581 82881 46585529
Exposure during pregnancy 18.32 17.20 9 17643 108203 46560207
Fatigue 17.92 17.20 326 17326 608371 46060039
Allergy to chemicals 17.89 17.20 8 17644 859 46667551
Oral candidiasis 17.56 17.20 27 17625 17505 46650905
Ascites 17.40 17.20 41 17611 36543 46631867

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 268.10 16.59 287 13659 106406 29832126
Neutrophil count decreased 127.56 16.59 126 13820 42328 29896204
White blood cell count decreased 88.57 16.59 148 13798 83799 29854733
Drug ineffective 87.96 16.59 25 13921 340362 29598170
Pyrexia 81.92 16.59 311 13635 294178 29644354
Leukopenia 71.57 16.59 108 13838 56051 29882481
Platelet count decreased 70.86 16.59 154 13792 105975 29832557
Neutropenia 62.58 16.59 165 13781 128375 29810157
Vomiting 57.54 16.59 228 13718 219590 29718942
Stomatitis 56.70 16.59 78 13868 37201 29901331
Nausea 52.34 16.59 274 13672 296683 29641849
Mucosal disorder 50.30 16.59 21 13925 1546 29936986
Decreased appetite 42.82 16.59 160 13786 149750 29788782
Interstitial lung disease 42.00 16.59 89 13857 60108 29878424
Disseminated intravascular coagulation 40.85 16.59 51 13895 22120 29916412
Sepsis 40.77 16.59 155 13791 146240 29792292
Diarrhoea 38.34 16.59 276 13670 333827 29604705
Thrombocytopenia 35.62 16.59 142 13804 136902 29801630
Polyneuropathy 35.28 16.59 35 13911 11788 29926744
Fall 34.55 16.59 21 13925 181851 29756681
Antithrombin III decreased 34.22 16.59 11 13935 383 29938149
Colorectal cancer 32.21 16.59 16 13930 1763 29936769
General physical health deterioration 29.60 16.59 108 13838 99836 29838696
Constipation 29.32 16.59 117 13829 112789 29825743
C-reactive protein increased 28.84 16.59 63 13883 43410 29895122
Disease progression 28.63 16.59 92 13854 79782 29858750
Dermatitis acneiform 27.24 16.59 22 13924 5667 29932865
Product dose omission issue 27.00 16.59 5 13941 91626 29846906
Blast cell count increased 26.91 16.59 12 13934 1037 29937495
Hiccups 26.44 16.59 27 13919 9407 29929125
Drug therapeutic incompatibility 25.95 16.59 7 13939 130 29938402
Tumour perforation 24.98 16.59 8 13938 275 29938257
Acute graft versus host disease in skin 24.94 16.59 19 13927 4497 29934035
Anaemia 23.85 16.59 172 13774 207820 29730712
Lymphocyte count decreased 23.32 16.59 36 13910 19019 29919513
Enterocolitis 22.21 16.59 21 13925 6666 29931866
Myocardial infarction 21.82 16.59 16 13930 125609 29812923
Hepatic function abnormal 21.52 16.59 55 13891 41890 29896642
Off label use 21.42 16.59 193 13753 249097 29689435
Non-small cell lung cancer 21.27 16.59 16 13930 3714 29934818
Toxicity to various agents 21.25 16.59 31 13915 177152 29761380
Pneumonia 21.17 16.59 243 13703 334063 29604469
Mucosal inflammation 21.14 16.59 45 13901 30449 29908083
Laryngeal leukoplakia 20.97 16.59 5 13941 55 29938477
Dehydration 20.94 16.59 113 13833 123426 29815106
Peripheral sensory neuropathy 20.50 16.59 19 13927 5882 29932650
Ileus 19.90 16.59 30 13916 15525 29923007
Engraftment syndrome 19.69 16.59 9 13937 824 29937708
Nail bed inflammation 19.58 16.59 6 13940 178 29938354
Palmar-plantar erythrodysaesthesia syndrome 19.48 16.59 29 13917 14841 29923691
Fluid imbalance 18.78 16.59 7 13939 381 29938151
Pulpitis dental 18.47 16.59 7 13939 399 29938133
Arthralgia 18.06 16.59 22 13924 135769 29802763
Hypoalbuminaemia 18.05 16.59 24 13922 11068 29927464
Proteinuria 17.69 16.59 29 13917 16116 29922416
Ileal perforation 17.54 16.59 8 13938 729 29937803
Blood lactate dehydrogenase increased 17.39 16.59 33 13913 20568 29917964
Bone marrow failure 17.34 16.59 41 13905 29744 29908788
Cardiac failure congestive 17.07 16.59 9 13937 84398 29854134

Pharmacologic Action:

SourceCodeDescription
ATC A04AA02 ALIMENTARY TRACT AND METABOLISM
ANTIEMETICS AND ANTINAUSEANTS
ANTIEMETICS AND ANTINAUSEANTS
Serotonin (5HT3) antagonists
FDA MoA N0000175817 Serotonin 3 Receptor Antagonists
FDA EPC N0000175818 Serotonin-3 Receptor Antagonist
CHEBI has role CHEBI:48279 serotonin antagonists
CHEBI has role CHEBI:50919 antiemetico
MeSH PA D000932 Antiemetics
MeSH PA D002491 Central Nervous System Agents
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018490 Serotonin Agents
MeSH PA D012702 Serotonin Antagonists

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Post-Operative Nausea and Vomiting indication 1488000
Chemotherapy-induced nausea and vomiting indication 236084000
Prevention of Post-Operative Nausea and Vomiting indication
Prevention of Radiation-Induced Nausea and Vomiting indication
Prolonged-Severe Nausea and Vomiting off-label use
Hypokalemia contraindication 43339004
Conduction disorder of the heart contraindication 44808001
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Congenital long QT syndrome contraindication 442917000
Doxorubicin Induced Cardiomyopathy contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.79 acidic
pKa2 9.5 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
5-hydroxytryptamine receptor 3A Ion channel ANTAGONIST Ki 8.70 WOMBAT-PK CHEMBL
Neuronal acetylcholine receptor; alpha4/beta2 Ion channel Ki 4.42 CHEMBL
Solute carrier family 22 member 2 Transporter IC50 5.37 CHEMBL
Neuronal acetylcholine receptor subunit alpha-3 Ion channel Ki 4.17 CHEMBL
5-hydroxytryptamine receptor 3B Ion channel Ki 8.80 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 5.30 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.43 WOMBAT-PK
Serotonin 3 (5-HT3) receptor Ion channel Ki 9.46 CHEMBL

External reference:

IDSource
4020855 VUID
N0000179527 NUI
D00677 KEGG_DRUG
107007-99-8 SECONDARY_CAS_RN
4020855 VANDF
4023910 VANDF
C0733443 UMLSCUI
CHEBI:5537 CHEBI
CWB PDB_CHEM_ID
CHEMBL289469 ChEMBL_ID
CHEMBL1237080 ChEMBL_ID
DB00889 DRUGBANK_ID
D017829 MESH_DESCRIPTOR_UI
5284566 PUBCHEM_CID
2300 IUPHAR_LIGAND_ID
6230 INN_ID
WZG3J2MCOL UNII
142149 RXNORM
130105 MMSL
157872 MMSL
25895 MMSL
4801 MMSL
d03171 MMSL
003975 NDDF
003976 NDDF
108424001 SNOMEDCT_US
108425000 SNOMEDCT_US
372489005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-0143 TABLET 1 mg ORAL ANDA 19 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0143-9744 INJECTION 1 mg INTRAVENOUS ANDA 25 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0143-9745 INJECTION 1 mg INTRAVENOUS ANDA 25 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-221 TABLET, FILM COATED 1 mg ORAL ANDA 20 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-221 TABLET, FILM COATED 1 mg ORAL ANDA 20 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17478-546 INJECTION 1 mg INTRAVENOUS ANDA 26 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17478-547 INJECTION 0.10 mg INTRAVENOUS ANDA 26 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42043-390 TABLET, FILM COATED 1 mg ORAL ANDA 20 sections
SANCUSO HUMAN PRESCRIPTION DRUG LABEL 1 42747-726 PATCH 3.10 mg TRANSDERMAL NDA 31 sections
SUSTOL HUMAN PRESCRIPTION DRUG LABEL 1 47426-101 INJECTION 10 mg SUBCUTANEOUS NDA 27 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51991-735 TABLET 1 mg ORAL ANDA 21 sections
Sancuso HUMAN PRESCRIPTION DRUG LABEL 1 54868-5985 PATCH 3.10 mg TRANSDERMAL NDA 26 sections
Granisetron Hydrochloride Human Prescription Drug Label 1 55150-175 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Granisetron Hydrochloride Human Prescription Drug Label 1 55150-176 INJECTION, SOLUTION 4 mg INTRAVENOUS ANDA 24 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 55648-661 INJECTION 1 mg INTRAVENOUS ANDA 16 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 55648-661 INJECTION 1 mg INTRAVENOUS ANDA 16 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 55648-662 INJECTION 0.10 mg INTRAVENOUS ANDA 16 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63126-331 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 26 sections
Granisetron HUMAN PRESCRIPTION DRUG LABEL 1 63323-317 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 25 sections
Granisetron HUMAN PRESCRIPTION DRUG LABEL 1 63323-318 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Granisetron HUMAN PRESCRIPTION DRUG LABEL 1 63323-319 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Granisetron hydrochloride Human Prescription Drug Label 1 63850-0005 TABLET, FILM COATED 1 mg ORAL ANDA 18 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 64679-661 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 64679-662 INJECTION 0.10 mg INTRAVENOUS ANDA 23 sections
GRANISETRON HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 64679-841 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-861 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 24 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-863 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Granisetron Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-864 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Granisetron Hydrochloride Human Prescription Drug Label 1 67877-184 TABLET 1 mg ORAL ANDA 16 sections