topotecan 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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) 91 mg/mL Bocci G, Oprea TI, Benet LZ
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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.197 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 11.722 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 3.350 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.648 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 75.550 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 82.150 % High 1
herg hERG pIC50 4.601 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.469 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.420 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 69.030 % High 1
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 11.695 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 14.028 High 1
mh-clint Mouse hepatocyte intrinsic clearance 5.309 High 1
mppb Mouse plasma protein binding (% unbound) 72.550 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 17.701 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 81.400 % High 1
rat-kpuu-brain Rat brain Kpuu 0.030 % High 1
rh-clint Rat hepatocyte intrinsic clearance 2.871 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 83.620 % High 1
rppb Rat plasma protein binding (% unbound) 66.920 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 847.227 uM High 1

Approvals:

DateAgencyCompanyOrphan
May 28, 1996 FDA NOVARTIS PHARMS CORP
Nov. 12, 1996 EMA SANDOZ PHARMACEUTICALS D.D.

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 379.69 32.44 216 8277 158133 90461821
Anaemia 370.15 32.44 287 8206 352515 90267439
Neutropenia 270.74 32.44 199 8294 224705 90395249
Disease progression 221.47 32.44 153 8340 156462 90463492
Thrombocytopenia 214.15 32.44 168 8325 208557 90411397
Malignant neoplasm progression 206.42 32.44 127 8366 106743 90513211
Neutrophil count decreased 202.29 32.44 109 8384 71423 90548531
White blood cell count decreased 196.61 32.44 146 8347 166963 90452991
Platelet count decreased 182.31 32.44 129 8364 136840 90483114
Ascites 164.25 32.44 83 8410 47657 90572297
Pancytopenia 157.06 32.44 112 8381 120151 90499803
Metastases to liver 122.79 32.44 58 8435 28749 90591205
Red blood cell count decreased 115.43 32.44 65 8428 46286 90573668
Neoplasm progression 104.36 32.44 60 8433 44426 90575528
Therapy partial responder 102.05 32.44 47 8446 21996 90597958
Product use in unapproved indication 98.00 32.44 138 8355 336098 90283856
Ileus 91.65 32.44 40 8453 16506 90603448
Metastases to central nervous system 86.22 32.44 39 8454 17503 90602451
Haematotoxicity 85.04 32.44 35 8458 12500 90607454
Metastases to lymph nodes 83.96 32.44 34 8459 11655 90608299
Metastases to peritoneum 83.66 32.44 26 8467 4129 90615825
Pyrexia 77.05 32.44 182 8311 660303 89959651
Leukopenia 70.05 32.44 65 8428 100645 90519309
Acute myeloid leukaemia 62.61 32.44 33 8460 20607 90599347
Mucosal inflammation 62.38 32.44 48 8445 57577 90562377
Choroidal infarction 58.17 32.44 10 8483 107 90619847
Febrile bone marrow aplasia 55.41 32.44 24 8469 9714 90610240
Decreased appetite 53.00 32.44 112 8381 376428 90243526
Epistaxis 49.85 32.44 50 8443 85075 90534879
Ovarian cancer recurrent 49.76 32.44 14 8479 1576 90618378
Venoocclusive liver disease 48.49 32.44 19 8474 5974 90613980
Nausea 46.57 32.44 216 8277 1110100 89509854
Ovarian cancer 46.25 32.44 19 8474 6748 90613206
Alveolar soft part sarcoma 45.47 32.44 8 8485 99 90619855
Vomiting 45.27 32.44 169 8324 788124 89831830
Off label use 45.17 32.44 213 8280 1102039 89517915
Hydronephrosis 43.88 32.44 22 8471 12380 90607574
Myelodysplastic syndrome 43.22 32.44 26 8467 20877 90599077
Arthralgia 41.37 32.44 11 8482 778511 89841443
Dehydration 41.25 32.44 69 8424 194378 90425576
Metapneumovirus infection 38.37 32.44 11 8482 1324 90618630
Subileus 38.34 32.44 14 8479 3630 90616324
Bone marrow failure 37.42 32.44 28 8465 32193 90587761
Lymphopenia 36.14 32.44 24 8469 22857 90597097
Death 35.04 32.44 108 8385 456443 90163511
Gastrointestinal perforation 32.48 32.44 13 8480 4319 90615635

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 305.34 30.35 230 5613 185473 42430019
Neoplasm progression 161.61 30.35 79 5764 28921 42586571
Thrombocytopenia 145.15 30.35 153 5690 190126 42425366
Anaplastic lymphoma kinase gene mutation 142.53 30.35 23 5820 103 42615389
Product use in unapproved indication 141.89 30.35 149 5694 184307 42431185
Anal inflammation 131.34 30.35 35 5808 2194 42613298
SARS-CoV-2 test negative 124.46 30.35 32 5811 1743 42613749
Neutropenia 112.17 30.35 137 5706 199294 42416198
Proctalgia 109.78 30.35 40 5803 7053 42608439
Haematotoxicity 102.78 30.35 43 5800 10942 42604550
Accident 101.86 30.35 37 5806 6466 42609026
White blood cell count decreased 84.28 30.35 89 5754 110307 42505185
Retinal degeneration 81.26 30.35 19 5824 694 42614798
Body temperature increased 77.53 30.35 43 5800 20315 42595177
Pancytopenia 74.44 30.35 86 5757 117657 42497835
Anaemia 71.34 30.35 133 5710 280145 42335347
Haemorrhoids 70.31 30.35 38 5805 17059 42598433
Choroidal infarction 63.15 30.35 11 5832 84 42615408
Small cell lung cancer 60.97 30.35 19 5824 2076 42613416
Pyrexia 60.10 30.35 152 5691 393890 42221602
Rhabdomyosarcoma recurrent 58.43 30.35 11 5832 135 42615357
Primitive neuroectodermal tumour 56.67 30.35 10 5833 83 42615409
Neoplasm recurrence 56.06 30.35 19 5824 2705 42612787
Febrile bone marrow aplasia 54.44 30.35 27 5816 10154 42605338
Platelet count decreased 50.05 30.35 77 5766 138504 42476988
Cardiotoxicity 49.71 30.35 23 5820 7422 42608070
Disease progression 47.97 30.35 77 5766 143579 42471913
Neuroblastoma recurrent 47.06 30.35 11 5832 401 42615091
Malignant neoplasm progression 44.52 30.35 64 5779 108336 42507156
Vitreous haemorrhage 44.39 30.35 16 5827 2731 42612761
Retinopathy proliferative 43.38 30.35 8 5835 87 42615405
Acute myeloid leukaemia 39.41 30.35 29 5814 22227 42593265
Product use issue 37.03 30.35 49 5794 76702 42538790
Off label use 35.17 30.35 176 5667 638159 41977333
Exophthalmos 34.55 30.35 10 5833 848 42614644
Neutrophil count decreased 34.54 30.35 43 5800 63372 42552120
Myelitis transverse 34.15 30.35 11 5832 1336 42614156
Vomiting 32.37 30.35 100 5743 289623 42325869
Chromosome analysis abnormal 31.56 30.35 7 5836 201 42615291

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 603.27 25.76 396 11885 316371 110260647
Anaemia 332.43 25.76 353 11928 546733 110030285
Neutropenia 286.31 25.76 274 12007 374346 110202672
Thrombocytopenia 285.38 25.76 265 12016 348620 110228398
White blood cell count decreased 259.86 25.76 210 12071 229180 110347838
Product use in unapproved indication 231.92 25.76 266 12015 447111 110129907
Malignant neoplasm progression 215.07 25.76 168 12113 174399 110402619
Pancytopenia 214.53 25.76 181 12100 209432 110367586
Platelet count decreased 205.60 25.76 184 12097 230259 110346759
Neutrophil count decreased 204.62 25.76 141 12140 120800 110456218
Neoplasm progression 200.66 25.76 111 12170 64484 110512534
Disease progression 194.62 25.76 183 12098 243851 110333167
Anaplastic lymphoma kinase gene mutation 143.03 25.76 23 12258 129 110576889
Metastases to liver 132.83 25.76 69 12212 35317 110541701
Anal inflammation 129.85 25.76 34 12247 2462 110574556
Red blood cell count decreased 126.09 25.76 83 12198 65840 110511178
Choroidal infarction 121.02 25.76 21 12260 198 110576820
SARS-CoV-2 test negative 120.09 25.76 31 12250 2122 110574896
Pyrexia 111.13 25.76 281 12000 897984 109679034
Metastases to lymph nodes 101.70 25.76 44 12237 14988 110562030
Ascites 100.67 25.76 83 12198 92725 110484293
Haematotoxicity 96.40 25.76 47 12234 21035 110555983
Proctalgia 93.72 25.76 40 12241 13182 110563836
Accident 87.23 25.76 36 12245 10916 110566102
Acute myeloid leukaemia 85.29 25.76 53 12228 38057 110538961
Metastases to peritoneum 71.66 25.76 26 12255 5584 110571434
Metastases to central nervous system 70.21 25.76 39 12242 22778 110554240
Off label use 66.79 25.76 335 11946 1499850 109077168
Metastases to bone 66.10 25.76 42 12239 31330 110545688
Retinal degeneration 64.60 25.76 18 12263 1648 110575370
Arthralgia 62.23 25.76 7 12274 779625 109797393
Cardiotoxicity 57.88 25.76 31 12250 16850 110560168
Body temperature increased 57.36 25.76 48 12233 54665 110522353
Neuroblastoma recurrent 56.99 25.76 13 12268 527 110576491
Myelodysplastic syndrome 50.24 25.76 38 12243 37446 110539572
Haemorrhoids 49.68 25.76 37 12244 35635 110541383
Vomiting 48.82 25.76 215 12066 910460 109666558
Myelosuppression 48.43 25.76 56 12225 94284 110482734
Leukopenia 47.70 25.76 70 12211 148721 110428297
Decreased appetite 47.61 25.76 138 12143 475708 110101310
Rhabdomyosarcoma recurrent 46.96 25.76 9 12272 153 110576865
Small cell lung cancer 44.93 25.76 16 12265 3256 110573762
Neoplasm recurrence 44.39 25.76 18 12263 5214 110571804
Vitreous haemorrhage 43.03 25.76 17 12264 4603 110572415
Retinopathy proliferative 40.95 25.76 8 12273 151 110576867
Febrile bone marrow aplasia 40.87 25.76 25 12256 17440 110559578
Ovarian cancer 40.33 25.76 16 12265 4380 110572638
Venoocclusive liver disease 38.77 25.76 23 12258 15184 110561834
Alveolar soft part sarcoma 38.14 25.76 7 12274 93 110576925
Joint swelling 37.88 25.76 3 12278 442842 110134176
Lymphopenia 37.53 25.76 33 12248 40137 110536881
Dehydration 36.99 25.76 90 12191 279421 110297597
Neuroblastoma 34.30 25.76 8 12273 358 110576660
Pruritus 34.23 25.76 11 12270 581549 109995469
Deafness neurosensory 33.92 25.76 18 12263 9601 110567417
Haemoglobin decreased 33.88 25.76 81 12200 248646 110328372
VIth nerve paralysis 33.49 25.76 11 12270 1756 110575262
Abdominal discomfort 32.77 25.76 3 12278 393855 110183163
Protein total decreased 31.83 25.76 18 12263 10872 110566146
Therapy partial responder 31.76 25.76 29 12252 37032 110539986
Hypoalbuminaemia 31.57 25.76 26 12255 28948 110548070
Ileus 30.23 25.76 26 12255 30703 110546315
Myelitis transverse 30.19 25.76 11 12270 2390 110574628
Clostridium colitis 30.18 25.76 12 12269 3303 110573715
Metapneumovirus infection 30.00 25.76 11 12270 2433 110574585
Drug hypersensitivity 29.68 25.76 7 12274 454083 110122935
Choroidal dystrophy 29.44 25.76 5 12276 41 110576977
Peripheral swelling 28.96 25.76 5 12276 404029 110172989
Retinal detachment 28.85 25.76 17 12264 11083 110565935
Leukocoria 28.38 25.76 4 12277 7 110577011
Anxiety 27.73 25.76 3 12278 345075 110231943
Exophthalmos 27.05 25.76 10 12271 2263 110574755
Drug interaction 26.81 25.76 11 12270 500172 110076846
Infusion related reaction 26.71 25.76 5 12276 381157 110195861
Mucosal inflammation 26.24 25.76 42 12239 96099 110480919
Cutaneous lupus erythematosus 26.20 25.76 11 12270 3477 110573541
Blood bilirubin increased 26.17 25.76 37 12244 75935 110501083
Death 26.01 25.76 149 12132 698720 109878298
Swelling 25.93 25.76 4 12277 351037 110225981
Bone marrow failure 25.83 25.76 32 12249 57816 110519202
Rash 25.81 25.76 32 12249 820932 109756086
Heterochromia iridis 25.79 25.76 4 12277 17 110577001

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
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D059004 Topoisomerase I Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50276 EC 5.99.1.2 (DNA topoisomerase) inhibitor

Related Drugs by ATC class:

L01CE Topoisomerase 1 (TOP1) inhibitors 2 drugs
belotecanirinotecan

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




🐶 Veterinary Drug Use

None

🐶 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 Nuclear other 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
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
24611 MMSL
5446 MMSL
5602 MMSL
d04014 MMSL
005981 NDDF
005982 NDDF
108779005 SNOMEDCT_US
108781007 SNOMEDCT_US
372536007 SNOMEDCT_US
TTC PDB_CHEM_ID
7M7YKX2N15 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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 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 27 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 66758-101 CAPSULE 0.25 mg ORAL NDA 29 sections
HYCAMTIN HUMAN PRESCRIPTION DRUG LABEL 1 66758-102 CAPSULE 1 mg ORAL NDA 29 sections
Topotecan HUMAN PRESCRIPTION DRUG LABEL 1 71288-127 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 4 mg INTRAVENOUS ANDA 26 sections