Scroll

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

Stem definition	Drug id	CAS RN
antineoplastics, topoisomerase I inhibitors	2707	123948-87-8

Description:

Molecule	Description
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

Molecule

Description

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:

Property	Value	Reference
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:

Date	Agency	Company	Orphan
May 28, 1996	FDA	NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
DNA topoisomerase I, mitochondrial	Enzyme	Q969P6	TOP1M_HUMAN	INHIBITOR			WOMBAT-PK	CHEMBL
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN				WOMBAT-PK
Canalicular multispecific organic anion transporter 1	Transporter	Q92887	MRP2_HUMAN				WOMBAT-PK
Nuclear receptor subfamily 1 group I member 2	Nuclear hormone receptor	O75469	NR1I2_HUMAN				WOMBAT-PK
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN				WOMBAT-PK
Multidrug resistance-associated protein 4	Transporter	O15439	MRP4_HUMAN				WOMBAT-PK
DNA topoisomerase 1	Enzyme	P11387	TOP1_HUMAN		Kd	7.58	CHEMBL
Hypoxia-inducible factor 1-alpha	Transcription factor	Q16665	HIF1A_HUMAN		IC50	7.22	CHEMBL
Solute carrier family 22 member 2	Transporter	O15244	S22A2_HUMAN		IC50	4.21	CHEMBL
Multidrug and toxin extrusion protein 1	Transporter	Q96FL8	S47A1_HUMAN		IC50	5.89	CHEMBL
Multidrug and toxin extrusion protein 2	Transporter	Q86VL8	S47A2_HUMAN		IC50	5.07	CHEMBL
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.82	DRUG MATRIX
DNA topoisomerase I	Enzyme		TOP1_MOUSE		IC50	4.70	CHEMBL
ORF 73	Unclassified		O40947_HHV8		AC50	5.67	CHEMBL
UDP-galactopyranose mutase	Enzyme		GLF_MYCTU		AC50	5.16	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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