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

Stem definitionDrug idCAS RN
antineoplastics, topoisomerase I inhibitors 2707 123948-87-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nogitecan
  • potactasol
  • nogitecan hydrochloride
  • topotecan
  • (S)-Topotecan
  • hycamptamine
  • topotecan lactone
  • topotecan hydrochloride
  • hycamtin
  • nogitecan HCl
  • topotecan HCl
An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.
  • Molecular weight: 421.45
  • Formula: C23H23N3O5
  • CLOGP: 0.43
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 103.20
  • ALOGS: -2.69
  • ROTB: 3
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 40 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 6.16 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 32 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.80 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 13 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.65 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.30 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 28, 1996 FDA NOVARTIS PHARMS CORP

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
Anaemia 839.39 57.71 235 1090 34557 2322203
Thrombocytopenia 445.87 57.71 127 1198 19004 2337756
Neutrophil count decreased 443.17 57.71 102 1223 6465 2350295
White blood cell count decreased 415.57 57.71 119 1206 18089 2338671
Neutropenia 404.50 57.71 121 1204 21427 2335333
Platelet count decreased 367.75 57.71 105 1220 15708 2341052
Nausea 329.87 57.71 162 1163 112027 2244733
Red blood cell count decreased 296.30 57.71 68 1257 4198 2352562
Febrile neutropenia 282.87 57.71 79 1246 10803 2345957
Decreased appetite 270.47 57.71 96 1229 28795 2327965
Vomiting 219.22 57.71 107 1218 71495 2285265
Pancytopenia 199.33 57.71 61 1264 11391 2345369
Ascites 198.15 57.71 52 1273 5568 2351192
Pyrexia 190.54 57.71 89 1236 53619 2303141
Malignant neoplasm progression 187.48 57.71 59 1266 12069 2344691
Disease progression 183.10 57.71 63 1262 17032 2339728
General physical health deterioration 162.60 57.71 55 1270 14084 2342676
Ileus 157.82 57.71 36 1289 2136 2354624
Fatigue 154.75 57.71 90 1235 84783 2271977
Dehydration 141.67 57.71 56 1269 22239 2334521
Dyspnoea 136.75 57.71 81 1244 78652 2278108
Abdominal pain 127.66 57.71 59 1266 34315 2322445
Metastases to liver 112.09 57.71 29 1296 2912 2353848
Leukopenia 110.51 57.71 38 1287 10158 2346602
Bone marrow failure 105.96 57.71 32 1293 5654 2351106
Diarrhoea 104.68 57.71 70 1255 83494 2273266
Asthenia 96.31 57.71 54 1271 46872 2309888
Constipation 92.36 57.71 41 1284 21588 2335172
Ovarian cancer 91.20 57.71 21 1304 1292 2355468
Febrile bone marrow aplasia 88.68 57.71 19 1306 838 2355922
Pleural effusion 83.41 57.71 32 1293 11636 2345124
Metastases to peritoneum 81.91 57.71 16 1309 442 2356318
Haemoglobin decreased 79.34 57.71 35 1290 18116 2338644
Mucosal inflammation 78.72 57.71 25 1300 5199 2351561
Death 77.98 57.71 58 1267 81410 2275350
Metastases to lymph nodes 75.18 57.71 17 1308 963 2355797
Desmoplastic small round cell tumour 71.62 57.71 9 1316 6 2356754
Choroidal infarction 64.26 57.71 9 1316 25 2356735
Pulmonary embolism 63.63 57.71 30 1295 18053 2338707
Metastases to central nervous system 61.92 57.71 17 1308 2131 2354629
Haematotoxicity 61.85 57.71 15 1310 1152 2355608
Subileus 60.99 57.71 13 1312 558 2356202
Hydronephrosis 60.62 57.71 15 1310 1252 2355508
Neuropathy peripheral 59.61 57.71 25 1300 11407 2345353

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
Thrombocytopenia 271.45 59.04 88 689 21161 1724843
Anaemia 243.26 59.04 88 689 29369 1716635
White blood cell count decreased 185.51 59.04 59 718 13090 1732914
Platelet count decreased 180.19 59.04 61 716 16462 1729542
Neutropenia 155.06 59.04 56 721 18204 1727800
Febrile neutropenia 152.96 59.04 49 728 11051 1734953
Haemoglobin decreased 135.89 59.04 50 727 17064 1728940
Neutrophil count decreased 131.38 59.04 38 739 6043 1739961
Pyrexia 131.17 59.04 65 712 46335 1699669
Febrile bone marrow aplasia 129.90 59.04 26 751 852 1745152
Product use in unapproved indication 114.98 59.04 38 739 9384 1736620
Small cell lung cancer 112.57 59.04 20 757 337 1745667
Pancytopenia 111.88 59.04 39 738 11318 1734686
Red blood cell count decreased 111.41 59.04 30 747 3656 1742348
Chorioretinal atrophy 107.57 59.04 15 762 42 1745962
Dehydration 98.56 59.04 40 737 17618 1728386
Blood lactate dehydrogenase increased 97.48 59.04 27 750 3648 1742356
Leukopenia 86.76 59.04 30 747 8450 1737554
Pneumonia 77.56 59.04 46 731 46136 1699868
Diarrhoea 76.05 59.04 48 729 53804 1692200
Choroidal infarction 71.95 59.04 10 767 27 1745977
Nausea 70.65 59.04 45 732 51151 1694853
Disease progression 69.27 59.04 31 746 17232 1728772
Malignant neoplasm progression 65.11 59.04 28 749 14130 1731874
Protein total decreased 64.95 59.04 14 763 657 1745347
Interstitial lung disease 64.51 59.04 25 752 9671 1736333
Vomiting 63.74 59.04 38 739 38277 1707727
Decreased appetite 62.61 59.04 32 745 23839 1722165
Sepsis 59.63 59.04 29 748 19409 1726595
Death 59.30 59.04 50 727 87393 1658611

Pharmacologic Action:

SourceCodeDescription
ATC L01XX17 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA EPC N0000175609 Topoisomerase Inhibitor
FDA MoA N0000000176 Topoisomerase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D059004 Topoisomerase I Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Small cell carcinoma of lung indication 254632001 DOID:5409
Malignant tumor of cervix indication 363354003 DOID:4362
Malignant tumor of ovary indication 363443007 DOID:2394
Ewing's sarcoma off-label use 76909002 DOID:3369
Refractory Osteosarcoma off-label use
Fibrosis of lung contraindication 51615001 DOID:3770
Diarrhea contraindication 62315008
Acute infectious disease contraindication 63171007
Interstitial pneumonia contraindication 64667001
Impaired renal function disorder contraindication 197663003
Interstitial lung disease contraindication 233703007 DOID:3082
Neutropenic colitis contraindication 235755005
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001
Severe Bone Marrow Depression contraindication
Radiation Therapy Involving the Lungs contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.44 acidic
pKa2 10.46 acidic
pKa3 11.03 Basic
pKa4 0.57 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
DNA topoisomerase I, mitochondrial Enzyme INHIBITOR WOMBAT-PK CHEMBL
Cytochrome P450 3A4 Enzyme IC50 5.82 DRUG MATRIX
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor WOMBAT-PK
Multidrug resistance-associated protein 4 Transporter WOMBAT-PK
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Canalicular multispecific organic anion transporter 1 Transporter WOMBAT-PK
Multidrug resistance protein 1 Transporter WOMBAT-PK
Solute carrier family 22 member 2 Transporter IC50 4.21 CHEMBL
DNA topoisomerase 1 Enzyme Kd 7.58 CHEMBL
Hypoxia-inducible factor 1-alpha Transcription factor IC50 7.22 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 5.07 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 5.89 CHEMBL
DNA topoisomerase I Unclassified IC50 4.70 CHEMBL
ORF 73 Unclassified AC50 5.67 CHEMBL
UDP-galactopyranose mutase Unclassified AC50 5.16 CHEMBL

External reference:

IDSource
4020977 VUID
N0000179716 NUI
C0886549 UMLSCUI
D02168 KEGG_DRUG
7M7YKX2N15 UNII
6783 INN_ID
108779005 SNOMEDCT_US
4024032 VANDF
005981 NDDF
169084 MMSL
57308 RXNORM
372536007 SNOMEDCT_US
d04014 MMSL
119413-54-6 SECONDARY_CAS_RN
CHEMBL84 ChEMBL_ID
DB01030 DRUGBANK_ID
CHEMBL1607 ChEMBL_ID
TTC PDB_CHEM_ID
CHEBI:63632 CHEBI
D019772 MESH_DESCRIPTOR_UI
60700 PUBCHEM_CID
7101 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0672 CAPSULE 0.25 mg ORAL NDA 19 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0673 CAPSULE 1 mg ORAL NDA 19 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0674 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS NDA 17 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 0409-0302 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS NDA 18 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 0703-4714 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS NDA 17 sections
topotecan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16729-151 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 17 sections
topotecan HUMAN PRESCRIPTION DRUG LABEL 1 25021-236 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS NDA 19 sections
Topotecan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45963-615 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 17 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 50742-404 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 18 sections
Topotecan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 55390-370 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 19 sections
Topotecan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63323-762 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 19 sections
TOPOTECAN HUMAN PRESCRIPTION DRUG LABEL 1 67457-662 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS ANDA 17 sections
TOPOTECAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 69097-262 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 17 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 71288-127 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 18 sections