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

Stem definition	Drug id	CAS RN
vinca alkaloids	2827	71486-22-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: vinorelbin ditartrate noranhydrovinblastine tartrate vinorelbine navelbin navelbine base 5'-anhydrovinblastine vinorelbine tartrate vinorelbine ditartrate navelbine vinorelbine base	A vinca alkaloid related to VINBLASTINE that is used as a first-line treatment for NON-SMALL CELL LUNG CANCER, or for advanced or metastatic BREAST CANCER refractory to treatment with ANTHRACYCLINES. Molecular weight: 778.95 Formula: C45H54N4O8 CLOGP: 5.94 LIPINSKI: 3 HAC: 12 HDO: 2 TPSA: 133.87 ALOGS: -4.81 ROTB: 10 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

vinorelbin ditartrate
noranhydrovinblastine tartrate
vinorelbine
navelbin
navelbine base
5'-anhydrovinblastine
vinorelbine tartrate
vinorelbine ditartrate
navelbine
vinorelbine base

A vinca alkaloid related to VINBLASTINE that is used as a first-line treatment for NON-SMALL CELL LUNG CANCER, or for advanced or metastatic BREAST CANCER refractory to treatment with ANTHRACYCLINES.

Molecular weight: 778.95
Formula: C45H54N4O8
CLOGP: 5.94
LIPINSKI: 3
HAC: 12
HDO: 2
TPSA: 133.87
ALOGS: -4.81
ROTB: 10

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)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	1000 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	11 %	Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability)	27 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	23 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	20 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.87 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	26 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 23, 1994	FDA	PIERRE FABRE

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
Malignant neoplasm progression	902.70	17.55	486	21071	64440	46600065
Disease progression	692.80	17.55	463	21094	90837	46573668
Metastases to liver	527.72	17.55	231	21326	19354	46645151
Metastases to bone	476.89	17.55	208	21349	17268	46647237
Neutropenia	446.18	17.55	431	21126	142773	46521732
Palmar-plantar erythrodysaesthesia syndrome	402.62	17.55	194	21363	20257	46644248
Breast cancer metastatic	344.69	17.55	154	21403	13524	46650981
Metastases to lung	264.90	17.55	119	21438	10577	46653928
Metastases to central nervous system	216.35	17.55	105	21452	11116	46653389
Metastases to lymph nodes	214.13	17.55	89	21468	6542	46657963
Breast cancer	196.50	17.55	165	21392	45353	46619152
Osteonecrosis	193.18	17.55	130	21427	25614	46638891
Febrile neutropenia	189.86	17.55	226	21331	94401	46570104
Mucosal inflammation	180.12	17.55	147	21410	38829	46625676
Osteonecrosis of jaw	176.57	17.55	138	21419	34264	46630241
Neoplasm progression	165.74	17.55	120	21437	26563	46637942
Haematotoxicity	146.17	17.55	69	21488	6864	46657641
Pseudocirrhosis	129.92	17.55	35	21522	653	46663852
Ejection fraction decreased	128.39	17.55	88	21469	17849	46646656
Neuropathy peripheral	111.57	17.55	171	21386	90722	46573783
Breast cancer recurrent	111.30	17.55	48	21509	3863	46660642
Pleural effusion	110.28	17.55	162	21395	82790	46581715
Metastases to skin	109.90	17.55	36	21521	1344	46663161
Metastases to peritoneum	104.27	17.55	41	21516	2607	46661898
Bone marrow failure	93.26	17.55	90	21467	29579	46634926
Neutropenic sepsis	87.09	17.55	60	21497	12264	46652241
Fall	84.05	17.55	24	21533	329073	46335432
Drug hypersensitivity	81.10	17.55	9	21548	243816	46420689
PIK3CA-activated mutation	78.89	17.55	23	21534	578	46663927
Ascites	77.58	17.55	90	21467	36494	46628011
Tooth extraction	72.91	17.55	50	21507	10143	46654362
Lymphoedema	70.64	17.55	46	21511	8566	46655939
Leukopenia	68.04	17.55	117	21440	68226	46596279
Neurotoxicity	65.98	17.55	53	21504	13664	46650841
Product dose omission issue	65.18	17.55	3	21554	168517	46495988
Tonsillar disorder	56.72	17.55	20	21537	936	46663569
Bone disorder	54.14	17.55	56	21501	19977	46644528
Debridement	53.49	17.55	21	21536	1329	46663176
Thrombocytopenia	49.07	17.55	149	21408	126432	46538073
Metastases to spine	48.29	17.55	24	21533	2670	46661835
Polyneuropathy	47.70	17.55	41	21516	11603	46652902
Therapy partial responder	45.89	17.55	28	21529	4654	46659851
Lymphangiosis carcinomatosa	45.75	17.55	18	21539	1146	46663359
Metastasis	45.40	17.55	27	21530	4285	46660220
Jaw operation	44.77	17.55	16	21541	779	46663726
Vessel puncture site bruise	44.54	17.55	13	21544	328	46664177
Skin toxicity	44.10	17.55	25	21532	3629	46660876
Death	44.03	17.55	285	21272	335263	46329242
Blood uric acid decreased	42.85	17.55	14	21543	518	46663987
Joint swelling	42.52	17.55	12	21545	166061	46498444
Stomatitis	42.50	17.55	96	21461	68201	46596304
Nasal disorder	40.50	17.55	20	21537	2194	46662311
Metastases to chest wall	40.32	17.55	13	21544	461	46664044
Sequestrectomy	40.24	17.55	16	21541	1047	46663458
Peripheral sensory neuropathy	39.39	17.55	29	21528	6574	46657931
Arthralgia	38.94	17.55	68	21489	364535	46299970
Cardiotoxicity	38.92	17.55	29	21528	6693	46657812
Urticaria	37.56	17.55	5	21552	117887	46546618
Tumour marker increased	36.83	17.55	22	21535	3519	46660986
Pruritus	36.36	17.55	35	21522	242317	46422188
Metastases to pleura	36.35	17.55	15	21542	1081	46663424
Eosinophil percentage increased	36.23	17.55	14	21543	849	46663656
Drug ineffective	36.11	17.55	176	21381	677662	45986843
Hypothalamo-pituitary disorder	35.72	17.55	13	21544	667	46663838
Gastrointestinal toxicity	35.19	17.55	23	21534	4308	46660197
Second primary malignancy	35.02	17.55	27	21530	6557	46657948
Metastases to soft tissue	34.47	17.55	9	21548	148	46664357
EGFR gene mutation	34.41	17.55	9	21548	149	46664356
Desmoplastic small round cell tumour	34.30	17.55	9	21548	151	46664354
Metastases to meninges	34.05	17.55	17	21540	1910	46662595
Superior vena cava syndrome	33.80	17.55	12	21545	573	46663932
Axillary pain	33.74	17.55	15	21542	1298	46663207
Off label use	33.59	17.55	294	21263	379547	46284958
Myelosuppression	33.34	17.55	28	21529	7675	46656830
Injection site pain	33.06	17.55	5	21552	107147	46557358
Osteomyelitis	33.05	17.55	46	21511	22337	46642168
Pyrexia	32.42	17.55	273	21284	348529	46315976
Somnolence	32.22	17.55	16	21541	156505	46508000
Invasive ductal breast carcinoma	32.17	17.55	25	21532	6143	46658362
Anaemia	32.12	17.55	215	21342	255564	46408941
Sinusitis	32.07	17.55	10	21547	129758	46534747
Portal hypertension	32.03	17.55	20	21537	3463	46661042
Pituitary tumour	31.97	17.55	13	21544	902	46663603
Metastatic neoplasm	31.46	17.55	20	21537	3573	46660932
Asthma	31.37	17.55	3	21554	91539	46572966
Loss of consciousness	31.30	17.55	6	21551	108232	46556273
Maternal exposure during pregnancy	31.15	17.55	5	21552	102544	46561961
Disease recurrence	30.37	17.55	40	21517	18431	46646074
General physical health deterioration	29.79	17.55	119	21438	115650	46548855
Drug interaction	29.68	17.55	30	21527	203064	46461441
Urinary tract infection	29.47	17.55	35	21522	220231	46444274
Neutrophil count decreased	29.22	17.55	63	21494	43363	46621142
Transaminases	29.17	17.55	7	21550	80	46664425
Decreased appetite	28.71	17.55	170	21387	193666	46470839
Condition aggravated	28.66	17.55	43	21514	245009	46419496
Blood lactate dehydrogenase increased	28.59	17.55	41	21516	20459	46644046
Bone lesion	27.94	17.55	21	21536	4910	46659595
Pneumonitis	27.40	17.55	48	21509	28372	46636133
Dermatitis exfoliative generalised	26.95	17.55	17	21540	2996	46661509
Weight increased	26.76	17.55	22	21535	164451	46500054
Headache	26.69	17.55	122	21435	478230	46186275
Osteolysis	26.58	17.55	16	21541	2596	46661909
Neutropenic infection	26.07	17.55	12	21545	1126	46663379
Constipation	25.98	17.55	153	21404	173944	46490561
Calcium ionised increased	25.62	17.55	7	21550	138	46664367
Hormone receptor positive breast cancer	25.32	17.55	9	21548	431	46664074
Overdose	24.94	17.55	8	21549	101971	46562534
Vomiting	24.71	17.55	318	21239	452476	46212029
Bone sequestrum	24.48	17.55	13	21544	1660	46662845
Gingivitis	23.97	17.55	23	21534	7497	46657008
Feeling abnormal	23.95	17.55	14	21543	125046	46539459
Anal erythema	23.43	17.55	7	21550	192	46664313
Neoplasm malignant	23.06	17.55	40	21517	23459	46641046
Memory impairment	22.98	17.55	4	21553	77333	46587172
Jaw disorder	22.94	17.55	19	21538	5111	46659394
Asthenia	22.57	17.55	231	21326	310844	46353661
Hypotension	22.48	17.55	46	21511	232543	46431962
Ejection fraction abnormal	22.29	17.55	9	21548	613	46663892
Vascular device infection	22.23	17.55	16	21541	3501	46661004
Hepatic failure	21.93	17.55	48	21509	33368	46631137
Jaundice	21.92	17.55	44	21513	28801	46635704
Injection site erythema	21.79	17.55	4	21553	74423	46590082
Ileus paralytic	21.42	17.55	17	21540	4306	46660199
Exposed bone in jaw	21.21	17.55	15	21542	3193	46661312
Exposure during pregnancy	20.88	17.55	12	21545	108200	46556305
Cardiac cirrhosis	20.88	17.55	6	21551	143	46664362
Bone pain	20.83	17.55	58	21499	46832	46617673
Drug resistance	20.32	17.55	32	21525	17336	46647169
Abdominal discomfort	20.23	17.55	24	21533	151141	46513364
Scintillating scotoma	20.20	17.55	6	21551	161	46664344
Diffuse large B-cell lymphoma recurrent	20.17	17.55	11	21546	1481	46663024
Blood creatinine decreased	20.16	17.55	17	21540	4687	46659818
Ectropion	19.89	17.55	6	21551	170	46664335
Malignant pleural effusion	19.84	17.55	13	21544	2445	46662060
Acute myeloid leukaemia	19.76	17.55	30	21527	15748	46648757
Hyperbaric oxygen therapy	19.70	17.55	5	21552	73	46664432
Joint ankylosis	19.66	17.55	8	21549	556	46663949
Pancytopenia	19.18	17.55	84	21473	84974	46579531
Bronchitis	18.73	17.55	13	21544	105966	46558539
Musculoskeletal stiffness	18.72	17.55	11	21546	97982	46566523
Primary mediastinal large B-cell lymphoma	18.55	17.55	4	21553	27	46664478
Recurrent cancer	18.48	17.55	11	21546	1748	46662757
Hyperplasia	18.28	17.55	8	21549	667	46663838
Bone marrow infiltration	18.17	17.55	7	21550	421	46664084
Atrial fibrillation	17.93	17.55	13	21544	103577	46560928
Sensory disturbance	17.79	17.55	25	21532	12242	46652263
Metastases to the mediastinum	17.58	17.55	7	21550	460	46664045

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
Neutropenia	166.50	20.43	165	5937	128375	29818001
Neutropenic sepsis	112.14	20.43	52	6050	11357	29935019
Malignant neoplasm progression	89.94	20.43	91	6011	72196	29874180
Febrile neutropenia	77.96	20.43	102	6000	106591	29839785
Leukopenia	75.91	20.43	74	6028	56085	29890291
Interstitial lung disease	71.59	20.43	74	6028	60123	29886253
Disease progression	64.01	20.43	80	6022	79794	29866582
Off label use	58.65	20.43	145	5957	249145	29697231
Radiation pneumonitis	58.35	20.43	20	6082	1976	29944400
Febrile bone marrow aplasia	52.99	20.43	28	6074	8069	29938307
Neoplasm progression	52.24	20.43	37	6065	17986	29928390
Autoimmune neutropenia	41.35	20.43	10	6092	281	29946095
Metastases to central nervous system	38.84	20.43	22	6080	7262	29939114
Non-small cell lung cancer	36.61	20.43	17	6085	3713	29942663
Cytomegalovirus chorioretinitis	35.56	20.43	16	6086	3252	29943124
Metastases to bone	35.55	20.43	23	6079	9635	29936741
Pneumonitis	34.85	20.43	35	6067	27419	29918957
Metastases to lung	34.59	20.43	21	6081	7874	29938502
Extravasation	33.57	20.43	13	6089	1815	29944561
Agranulocytosis	33.56	20.43	31	6071	21911	29924465
Pyrexia	33.32	20.43	133	5969	294356	29652020
Product leakage	29.91	20.43	8	6094	339	29946037
Metastases to the mediastinum	29.46	20.43	7	6095	182	29946194
Pancytopenia	28.33	20.43	57	6045	84995	29861381
Neutropenic colitis	27.75	20.43	12	6090	2218	29944158
Bone marrow failure	27.33	20.43	32	6070	29753	29916623
Hypophosphataemia	26.39	20.43	18	6084	8227	29938149
Lung adenocarcinoma	26.32	20.43	14	6088	4085	29942291
Myelosuppression	25.88	20.43	17	6085	7305	29939071
General physical health deterioration	24.26	20.43	59	6043	99885	29846491
Tracheal fistula	23.41	20.43	5	6097	79	29946297
Thrombocytopenia	23.34	20.43	71	6031	136973	29809403
Autoimmune pancytopenia	22.69	20.43	5	6097	92	29946284
PIK3CA-activated mutation	22.54	20.43	5	6097	95	29946281
Systemic candida	22.27	20.43	11	6091	2753	29943623
Embryonal rhabdomyosarcoma	21.81	20.43	4	6098	27	29946349
Bacterial infection	21.61	20.43	19	6083	12591	29933785
Recall phenomenon	21.47	20.43	7	6095	592	29945784
Streptococcal endocarditis	20.90	20.43	4	6098	35	29946341
Product use in unapproved indication	20.60	20.43	46	6056	73647	29872729

Pharmacologic Action:

Source	Code	Description
ATC	L01CA04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS Vinca alkaloids and analogues
FDA CS	M0022674	Vinca Alkaloids
FDA EPC	N0000175612	Vinca Alkaloid
MeSH PA	D050256	Antimitotic Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D000972	Antineoplastic Agents, Phytogenic
MeSH PA	D050257	Tubulin Modulators
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:47868	photosensitising agent

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Non-small cell lung cancer	indication	254637007	DOID:3908
Kaposi's sarcoma	off-label use	109385007
Neoplasm of endometrium	off-label use	123844007	DOID:1380
Small cell carcinoma of lung	off-label use	254632001	DOID:5409
Metastatic Breast Carcinoma	off-label use
Disorder of lung	contraindication	19829001	DOID:850
Infectious disease	contraindication	40733004
Gastrointestinal perforation	contraindication	51875005
Hepatic failure	contraindication	59927004
Interstitial pneumonia	contraindication	64667001
Intestinal obstruction	contraindication	81060008	DOID:8437
Leukopenia	contraindication	84828003	DOID:615
Gastrointestinal obstruction	contraindication	126765001
Pregnancy, function	contraindication	289908002
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001
Hepatic Metastases	contraindication
Intestinal Ischemic Necrosis	contraindication
Severe Granulocytopenia	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.32	acidic
pKa2	13.35	acidic
pKa3	8.55	Basic
pKa4	7.39	Basic
pKa5	6.11	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
Tubulin beta	Tumour-associated antigen	P04350 P07437 P68371 Q13509 Q13885 Q3ZCM7 Q9BUF5 Q9BVA1 Q9H4B7	TBB1_HUMAN TBB2A_HUMAN TBB2B_HUMAN TBB3_HUMAN TBB4A_HUMAN TBB4B_HUMAN TBB5_HUMAN TBB6_HUMAN TBB8_HUMAN	INHIBITOR			SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	6	DRUG MATRIX
Substance-K receptor	GPCR	P21452	NK2R_HUMAN		Ki	6.27	DRUG MATRIX

External reference:

ID	Source
4023981	VUID
N0000021986	NUI
D01935	KEGG_DRUG
125317-39-7	SECONDARY_CAS_RN
4020895	VANDF
4023981	VANDF
C0131965	UMLSCUI
CHEBI:480999	CHEBI
CHEMBL538943	ChEMBL_ID
CHEMBL553025	ChEMBL_ID
CHEMBL3039595	ChEMBL_ID
D000077235	MESH_DESCRIPTOR_UI
6054	INN_ID
Q6C979R91Y	UNII
5311497	PUBCHEM_CID
7105	IUPHAR_LIGAND_ID
DB00361	DRUGBANK_ID
114527	RXNORM
2135	MMSL
46388	MMSL
5676	MMSL
d03810	MMSL
004380	NDDF
004381	NDDF
108792008	SNOMEDCT_US
108794009	SNOMEDCT_US
372541004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Vinorelbine	HUMAN PRESCRIPTION DRUG LABEL	1	25021-204	INJECTION, SOLUTION	10 mg	INTRAVENOUS	ANDA	27 sections
Vinorelbine	HUMAN PRESCRIPTION DRUG LABEL	1	45963-607	INJECTION, SOLUTION	10 mg	INTRAVENOUS	ANDA	19 sections
Vinorelbine	HUMAN PRESCRIPTION DRUG LABEL	1	50742-420	INJECTION	10 mg	INTRAVENOUS	ANDA	19 sections
Vinorelbine	HUMAN PRESCRIPTION DRUG LABEL	1	50742-427	INJECTION	50 mg	INTRAVENOUS	ANDA	19 sections
NULLVELBINE	HUMAN PRESCRIPTION DRUG LABEL	1	64370-532	INJECTION	10 mg	INTRAVENOUS	NDA	26 sections