topotecan ๐Ÿถ Veterinary Use | 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: 1.03
  • 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 ยตM/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 297.69 29.33 248 6104 252208 50346564
Neutrophil count decreased 206.06 29.33 105 6247 45921 50552851
Febrile neutropenia 202.32 29.33 135 6217 97532 50501240
Thrombocytopenia 174.16 29.33 137 6215 127536 50471236
White blood cell count decreased 171.71 29.33 131 6221 116591 50482181
Neutropenia 164.58 29.33 141 6211 147824 50450948
Platelet count decreased 143.55 29.33 111 6241 100615 50498157
Malignant neoplasm progression 123.87 29.33 87 6265 68037 50530735
Ascites 118.73 29.33 67 6285 35794 50562978
Red blood cell count decreased 114.14 29.33 64 6288 33771 50565001
Disease progression 101.59 29.33 89 6263 95777 50502995
Pancytopenia 88.97 29.33 78 6274 83952 50514820
Metastases to liver 84.44 29.33 44 6308 20060 50578712
Ileus 79.60 29.33 37 6315 13192 50585580
Product use in unapproved indication 64.54 29.33 76 6276 115743 50483029
Decreased appetite 63.42 29.33 100 6252 200823 50397949
Febrile bone marrow aplasia 58.70 29.33 24 6328 6287 50592485
Choroidal infarction 58.45 29.33 10 6342 75 50598697
Metastases to central nervous system 57.03 29.33 28 6324 11254 50587518
Metastases to peritoneum 56.97 29.33 19 6333 2814 50595958
Metastases to lymph nodes 56.22 29.33 24 6328 7000 50591772
Leukopenia 50.95 29.33 52 6300 67476 50531296
Pyrexia 50.58 29.33 132 6220 380071 50218701
Haematotoxicity 50.35 29.33 23 6329 7872 50590900
Hydronephrosis 45.58 29.33 22 6330 8519 50590253
Nausea 43.67 29.33 189 6163 705209 49893563
Alveolar soft part sarcoma 43.14 29.33 8 6344 99 50598673
Vomiting 40.36 29.33 138 6214 460620 50138152
Neoplasm progression 38.95 29.33 31 6321 29126 50569646
General physical health deterioration 38.26 29.33 66 6286 142368 50456404
Subileus 38.15 29.33 14 6338 2745 50596027
Dehydration 36.28 29.33 67 6285 152382 50446390
Ovarian cancer recurrent 35.15 29.33 10 6342 872 50597900
Myelodysplastic syndrome 33.82 29.33 22 6330 15110 50583662
Gastrointestinal perforation 33.18 29.33 13 6339 3048 50595724
Bone marrow failure 31.93 29.33 27 6325 27597 50571175
Arthralgia 31.81 29.33 8 6344 438694 50160078

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 146.30 31.58 116 3517 112124 29458770
Anaplastic lymphoma kinase gene mutation 139.23 31.58 22 3611 96 29570798
Product use in unapproved indication 137.81 31.58 101 3532 86774 29484120
Thrombocytopenia 117.98 31.58 111 3522 134712 29436182
Retinal degeneration 86.48 31.58 18 3615 426 29570468
Small cell lung cancer 66.39 31.58 19 3614 1733 29569161
Choroidal infarction 64.48 31.58 11 3622 83 29570811
Neoplasm recurrence 64.13 31.58 19 3614 1958 29568936
White blood cell count decreased 63.92 31.58 64 3569 83298 29487596
Febrile bone marrow aplasia 62.35 31.58 26 3607 7325 29563569
Cardiotoxicity 58.53 31.58 22 3611 4722 29566172
Pancytopenia 56.78 31.58 60 3573 83108 29487786
Neoplasm progression 54.85 31.58 32 3601 18580 29552314
Anaemia 53.02 31.58 91 3542 200860 29370034
Haematotoxicity 51.18 31.58 22 3611 6677 29564217
Neutropenia 49.11 31.58 70 3563 131641 29439253
Malignant neoplasm progression 46.37 31.58 51 3582 73808 29497086
Retinopathy proliferative 45.06 31.58 8 3625 78 29570816
Vitreous haemorrhage 42.78 31.58 14 3619 1999 29568895
Platelet count decreased 41.01 31.58 57 3576 104615 29466279
Disease progression 40.44 31.58 50 3583 81866 29489028
Primitive neuroectodermal tumour 39.83 31.58 7 3626 64 29570830
Rhabdomyosarcoma recurrent 37.58 31.58 7 3626 91 29570803
Blood lactate dehydrogenase increased 36.44 31.58 25 3608 19184 29551710
Exophthalmos 35.40 31.58 9 3624 523 29570371
Neutrophil count decreased 32.49 31.58 33 3600 43534 29527360
Protein total decreased 31.82 31.58 14 3619 4488 29566406

FDA Adverse Event Reporting System (Geriatric)

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 285.88 27.46 218 8176 187439 64302899
Anaemia 248.40 27.46 274 8120 378406 64111932
White blood cell count decreased 213.29 27.46 171 8223 157666 64332672
Neutrophil count decreased 208.62 27.46 128 8266 77068 64413270
Thrombocytopenia 200.81 27.46 192 8202 223609 64266729
Product use in unapproved indication 166.79 27.46 156 8238 176462 64313876
Pancytopenia 161.74 27.46 140 8254 143169 64347169
Platelet count decreased 158.07 27.46 148 8246 167563 64322775
Malignant neoplasm progression 149.52 27.46 121 8273 112750 64377588
Red blood cell count decreased 140.28 27.46 84 8310 48302 64442036
Anaplastic lymphoma kinase gene mutation 136.83 27.46 22 8372 102 64490236
Choroidal infarction 121.47 27.46 21 8373 162 64490176
Neutropenia 120.82 27.46 152 8242 239472 64250866
Disease progression 101.83 27.46 108 8286 141572 64348766
Metastases to liver 94.82 27.46 51 8343 23890 64466448
Neoplasm progression 93.19 27.46 61 8333 40903 64449435
Ascites 80.98 27.46 66 8328 61935 64428403
Metastases to lymph nodes 69.44 27.46 30 8364 8687 64481651
Retinal degeneration 64.88 27.46 17 8377 1050 64489288
Cardiotoxicity 64.71 27.46 30 8364 10244 64480094
Pyrexia 56.58 27.46 180 8214 558464 63931874
Decreased appetite 53.61 27.46 115 8279 281174 64209164
Metastases to peritoneum 52.11 27.46 19 8375 3528 64486810
Leukopenia 52.08 27.46 65 8329 101177 64389161
Metastases to central nervous system 50.53 27.46 28 8366 13884 64476454
Small cell lung cancer 45.69 27.46 16 8378 2645 64487693
Febrile bone marrow aplasia 44.61 27.46 24 8370 11231 64479107
Neoplasm recurrence 43.91 27.46 17 8377 3722 64486616
Myelosuppression 43.52 27.46 31 8363 23799 64466539
Retinopathy proliferative 42.06 27.46 8 8386 110 64490228
Metastases to bone 40.61 27.46 28 8366 20407 64469931
Arthralgia 40.51 27.46 5 8389 442255 64048083
Vitreous haemorrhage 39.72 27.46 15 8379 3070 64487268
Dehydration 39.40 27.46 87 8307 216676 64273662
Alveolar soft part sarcoma 37.03 27.46 7 8387 93 64490245
Protein total decreased 34.50 27.46 18 8376 7918 64482420
Haemoglobin decreased 33.99 27.46 77 8317 194986 64295352
Haematotoxicity 33.76 27.46 21 8373 12875 64477463
Acute myeloid leukaemia 33.25 27.46 28 8366 27435 64462903
Administration related reaction 29.20 27.46 6 8388 125 64490213
Myelodysplastic syndrome 29.10 27.46 26 8368 27553 64462785
Ileus 29.01 27.46 24 8370 22942 64467396
Blood lactate dehydrogenase increased 28.77 27.46 28 8366 33050 64457288
Leukocoria 27.74 27.46 4 8390 7 64490331
Choroidal dystrophy 27.66 27.46 5 8389 51 64490287

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01CE01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS
Topoisomerase 1 (TOP1) inhibitors
FDA MoA N0000000176 Topoisomerase Inhibitors
FDA EPC N0000175609 Topoisomerase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:50276 topoisomerase I inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D059004 Topoisomerase I Inhibitors

Drug Use | Suggest Off label Use Form| |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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

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
Multidrug resistance protein 1 Transporter WOMBAT-PK
Canalicular multispecific organic anion transporter 1 Transporter WOMBAT-PK
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor WOMBAT-PK
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Multidrug resistance-associated protein 4 Transporter WOMBAT-PK
DNA topoisomerase 1 Enzyme Kd 7.58 CHEMBL
Hypoxia-inducible factor 1-alpha Transcription factor IC50 7.22 CHEMBL
Solute carrier family 22 member 2 Transporter IC50 4.21 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 5.89 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 5.07 CHEMBL
Cytochrome P450 3A4 Enzyme IC50 5.82 DRUG MATRIX
DNA topoisomerase I Enzyme IC50 4.70 CHEMBL
ORF 73 Unclassified AC50 5.67 CHEMBL
UDP-galactopyranose mutase Enzyme AC50 5.16 CHEMBL

External reference:

IDSource
4020977 VUID
N0000179716 NUI
D02168 KEGG_DRUG
119413-54-6 SECONDARY_CAS_RN
4020977 VANDF
4024032 VANDF
C0146224 UMLSCUI
CHEBI:63632 CHEBI
TTC PDB_CHEM_ID
CHEMBL84 ChEMBL_ID
CHEMBL1607 ChEMBL_ID
D019772 MESH_DESCRIPTOR_UI
DB01030 DRUGBANK_ID
60700 PUBCHEM_CID
7101 IUPHAR_LIGAND_ID
6783 INN_ID
7M7YKX2N15 UNII
203472 RXNORM
169084 MMSL
178613 MMSL
5446 MMSL
5602 MMSL
d04014 MMSL
005981 NDDF
005982 NDDF
108779005 SNOMEDCT_US
108781007 SNOMEDCT_US
372536007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0672 CAPSULE 0.25 mg ORAL NDA 29 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0673 CAPSULE 1 mg ORAL NDA 29 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 0078-0674 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS NDA 27 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 0409-0302 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS NDA 30 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 0703-4714 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS NDA 24 sections
topotecan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16729-151 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 24 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 16729-243 INJECTION 1 mg INTRAVENOUS ANDA 27 sections
Topotecan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45963-615 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 28 sections
Topotecan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63323-762 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 28 sections
Topotecan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63323-762 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 28 sections
TOPOTECAN HUMAN PRESCRIPTION DRUG LABEL 1 67457-662 INJECTION, SOLUTION, CONCENTRATE 1 mg INTRAVENOUS ANDA 24 sections
TOPOTECAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 69097-262 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 24 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 71288-127 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 26 sections