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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)	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

Approvals:

Date	Agency	Company	Orphan
Nov. 12, 1996	EMA	SANDOZ PHARMACEUTICALS D.D.
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	332.16	30.33	270	6940	293160	63188652
Febrile neutropenia	307.54	30.33	182	7028	118267	63363545
Neutrophil count decreased	204.22	30.33	108	7102	56298	63425514
Neutropenia	197.08	30.33	161	7049	174844	63306968
Thrombocytopenia	189.20	30.33	148	7062	151009	63330803
White blood cell count decreased	188.96	30.33	143	7067	138961	63342851
Platelet count decreased	172.46	30.33	126	7084	115996	63365816
Malignant neoplasm progression	164.08	30.33	107	7103	82014	63399798
Ascites	158.81	30.33	82	7128	40646	63441166
Disease progression	138.09	30.33	113	7097	122645	63359167
Pancytopenia	125.60	30.33	97	7113	96836	63384976
Red blood cell count decreased	111.79	30.33	65	7145	40580	63441232
Metastases to liver	104.97	30.33	52	7158	23587	63458225
Product use in unapproved indication	94.89	30.33	109	7101	178971	63302841
Metastases to peritoneum	87.79	30.33	27	7183	3415	63478397
Metastases to lymph nodes	85.90	30.33	33	7177	8125	63473687
Ileus	82.46	30.33	38	7172	14687	63467125
Haematotoxicity	74.64	30.33	31	7179	9345	63472467
Pyrexia	74.22	30.33	164	7046	470314	63011498
Leukopenia	70.15	30.33	63	7147	77227	63404585
Decreased appetite	64.79	30.33	108	7102	250944	63230868
Choroidal infarction	59.45	30.33	10	7200	75	63481737
Febrile bone marrow aplasia	57.56	30.33	24	7186	7301	63474511
Metastases to central nervous system	55.71	30.33	28	7182	13077	63468735
Alveolar soft part sarcoma	43.94	30.33	8	7202	99	63481713
Hydronephrosis	43.04	30.33	22	7188	10640	63471172
Vomiting	42.89	30.33	150	7060	559467	62922345
Neoplasm progression	41.82	30.33	34	7176	36394	63445418
Subileus	41.28	30.33	15	7195	3164	63478648
Metapneumovirus infection	38.79	30.33	11	7199	1049	63480763
Myelodysplastic syndrome	38.77	30.33	24	7186	16730	63465082
Arthralgia	38.16	30.33	9	7201	569701	62912111
Nausea	36.70	30.33	192	7018	854279	62627533
Dehydration	36.14	30.33	68	7142	173286	63308526
Bone marrow failure	35.02	30.33	28	7182	29262	63452550
Ovarian cancer recurrent	34.73	30.33	10	7200	1007	63480805
Gastrointestinal perforation	32.78	30.33	13	7197	3478	63478334
Meningitis bacterial	31.82	30.33	10	7200	1357	63480455

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	228.29	30.49	168	4413	136681	34815669
Anaplastic lymphoma kinase gene mutation	143.58	30.49	23	4558	103	34952247
Product use in unapproved indication	140.93	30.49	119	4462	117380	34834970
Thrombocytopenia	115.56	30.49	121	4460	156126	34796224
Anal inflammation	85.16	30.49	22	4559	1278	34951072
Neutropenia	84.34	30.49	103	4478	156675	34795675
Retinal degeneration	82.62	30.49	18	4563	498	34951852
SARS-CoV-2 test negative	75.35	30.49	19	4562	1001	34951349
White blood cell count decreased	74.08	30.49	76	4505	95369	34856981
Neoplasm progression	71.32	30.49	42	4539	23258	34929092
Accident	70.19	30.49	26	4555	5021	34947329
Anaemia	68.70	30.49	115	4466	233220	34719130
Haematotoxicity	67.75	30.49	29	4552	8165	34944185
Choroidal infarction	63.65	30.49	11	4570	84	34952266
Small cell lung cancer	63.60	30.49	19	4562	1886	34950464
Proctalgia	63.48	30.49	25	4556	5698	34946652
Pancytopenia	61.87	30.49	69	4512	95088	34857262
Febrile bone marrow aplasia	61.17	30.49	27	4554	8182	34944168
Neoplasm recurrence	60.49	30.49	19	4562	2230	34950120
Cardiotoxicity	56.83	30.49	23	4558	5625	34946725
Platelet count decreased	53.75	30.49	72	4509	119645	34832705
Body temperature increased	52.33	30.49	31	4550	17337	34935013
Haemorrhoids	49.17	30.49	28	4553	14547	34937803
Malignant neoplasm progression	49.07	30.49	59	4522	87987	34864363
Pyrexia	48.79	30.49	123	4458	332890	34619460
Disease progression	48.49	30.49	65	4516	108012	34844338
Retinopathy proliferative	44.45	30.49	8	4573	79	34952271
Rhabdomyosarcoma recurrent	42.50	30.49	8	4573	103	34952247
Vitreous haemorrhage	39.63	30.49	14	4567	2359	34949991
Primitive neuroectodermal tumour	39.38	30.49	7	4574	64	34952286
Neutrophil count decreased	36.53	30.49	39	4542	51065	34901285
Exophthalmos	34.01	30.49	9	4572	574	34951776
Metastases to bone	32.52	30.49	20	4561	11950	34940400
Neuroblastoma	32.01	30.49	7	4574	197	34952153
Product use issue	31.38	30.49	40	4541	63176	34889174
Blood lactate dehydrogenase increased	30.97	30.49	25	4556	22965	34929385

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	468.93	27.66	315	9716	230684	79503673
Anaemia	295.61	27.66	319	9712	444696	79289661
White blood cell count decreased	239.13	27.66	194	9837	188094	79546263
Product use in unapproved indication	217.72	27.66	208	9823	250151	79484206
Thrombocytopenia	216.84	27.66	213	9818	265046	79469311
Neutrophil count decreased	208.83	27.66	136	9895	93823	79640534
Platelet count decreased	198.77	27.66	177	9854	194487	79539870
Neutropenia	184.64	27.66	203	9828	287507	79446850
Malignant neoplasm progression	178.55	27.66	143	9888	135847	79598510
Pancytopenia	175.68	27.66	154	9877	165591	79568766
Disease progression	146.57	27.66	146	9885	184216	79550141
Anaplastic lymphoma kinase gene mutation	141.58	27.66	23	10008	120	79734237
Red blood cell count decreased	129.49	27.66	84	9947	57429	79676928
Choroidal infarction	122.07	27.66	21	10010	163	79734194
Metastases to liver	116.01	27.66	61	9970	28253	79706104
Neoplasm progression	110.27	27.66	73	9958	51609	79682748
Metastases to lymph nodes	108.59	27.66	43	9988	10354	79724003
Ascites	102.32	27.66	81	9950	75481	79658876
Pyrexia	88.43	27.66	234	9797	678475	79055882
Anal inflammation	79.16	27.66	21	10010	1409	79732948
Metastases to peritoneum	78.72	27.66	27	10004	4345	79730012
SARS-CoV-2 test negative	65.85	27.66	18	10013	1353	79733004
Cardiotoxicity	63.66	27.66	31	10000	12208	79722149
Retinal degeneration	62.57	27.66	17	10014	1249	79733108
Haematotoxicity	62.31	27.66	33	9998	15486	79718871
Decreased appetite	58.17	27.66	131	9900	342287	79392070
Myelosuppression	54.08	27.66	43	9988	40253	79694104
Accident	53.98	27.66	25	10006	8806	79725551
Arthralgia	53.82	27.66	5	10026	571798	79162559
Leukopenia	51.16	27.66	68	9963	116445	79617912
Proctalgia	51.02	27.66	25	10006	9976	79724381
Metastases to bone	50.85	27.66	34	9997	24393	79709964
Metastases to central nervous system	47.16	27.66	28	10003	16347	79718010
Small cell lung cancer	44.98	27.66	16	10015	2864	79731493
Febrile bone marrow aplasia	44.80	27.66	25	10006	12995	79721362
Neoplasm recurrence	42.50	27.66	17	10014	4197	79730160
Retinopathy proliferative	41.38	27.66	8	10023	125	79734232
Vomiting	41.16	27.66	179	9852	665649	79068708
Vitreous haemorrhage	37.52	27.66	15	10016	3698	79730659
Alveolar soft part sarcoma	37.27	27.66	7	10024	93	79734264
Body temperature increased	36.70	27.66	36	9995	44384	79689973
Dehydration	34.58	27.66	88	9943	248099	79486258
Myelodysplastic syndrome	33.69	27.66	29	10002	30272	79704085
Haemoglobin decreased	33.30	27.66	81	9950	222038	79512319
Acute myeloid leukaemia	33.21	27.66	29	10002	30856	79703501
Protein total decreased	32.77	27.66	18	10013	9074	79725283
Metapneumovirus infection	32.04	27.66	11	10020	1773	79732584
Neuroblastoma recurrent	31.92	27.66	7	10024	208	79734149
Haemorrhoids	30.62	27.66	27	10004	29101	79705256
Rhabdomyosarcoma recurrent	29.40	27.66	6	10025	125	79734232
Leukocoria	27.88	27.66	4	10027	7	79734350
Choroidal dystrophy	27.83	27.66	5	10026	51	79734306

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
MeSH PA	D059003	Topoisomerase 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
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

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	0078-0672	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	0078-0673	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
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	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 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	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