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

Stem definition	Drug id	CAS RN
serotonin receptor antagonists (5-HT3)	1329	109889-09-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: granisetron monohydrochloride BRL-43694 granisetron sancuso kevatril granisetron hydrochloride granisetron HCl	A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients. Molecular weight: 312.42 Formula: C18H24N4O CLOGP: 1.72 LIPINSKI: 0 HAC: 5 HDO: 1 TPSA: 50.16 ALOGS: -2.86 ROTB: 2 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

granisetron monohydrochloride
BRL-43694
granisetron
sancuso
kevatril
granisetron hydrochloride
granisetron HCl

A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.

Molecular weight: 312.42
Formula: C18H24N4O
CLOGP: 1.72
LIPINSKI: 0
HAC: 5
HDO: 1
TPSA: 50.16
ALOGS: -2.86
ROTB: 2

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
2	mg	O
3	mg	P
3.10	mg	TD

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	100 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	11 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.03 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	60 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	3.70 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	9.10 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.35 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 29, 1993	FDA	ROCHE

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
Febrile neutropenia	392.94	17.20	308	17344	94319	46574091
Neutropenia	183.08	17.20	247	17405	142957	46525453
Neutrophil count decreased	155.77	17.20	130	17522	43296	46625114
Nausea	155.04	17.20	588	17064	686866	45981544
Drug ineffective	153.01	17.20	35	17617	677803	45990607
Pyrexia	121.90	17.20	347	17305	348455	46319955
General physical health deterioration	111.78	17.20	175	17477	115594	46552816
Vomiting	106.19	17.20	393	17259	452401	46216009
Death	103.05	17.20	319	17333	335229	46333181
Leukopenia	99.75	17.20	126	17526	68217	46600193
Platelet count decreased	86.67	17.20	144	17508	99880	46568530
White blood cell count decreased	77.14	17.20	146	17506	112085	46556325
Decreased appetite	67.58	17.20	193	17459	193643	46474767
Stomatitis	65.49	17.20	103	17549	68194	46600216
Constipation	58.39	17.20	171	17481	173926	46494484
Disease progression	54.51	17.20	112	17540	91188	46577222
Diarrhoea	53.13	17.20	377	17275	559225	46109185
Polyneuropathy	52.71	17.20	40	17612	11604	46656806
Anaemia	52.28	17.20	213	17439	255566	46412844
Tooth erosion	47.05	17.20	14	17638	465	46667945
Thrombocytopenia	45.96	17.20	128	17524	126453	46541957
Pancytopenia	45.74	17.20	100	17552	84958	46583452
Joint swelling	45.24	17.20	5	17647	166068	46502342
Completed suicide	43.51	17.20	3	17649	145917	46522493
Drug hypersensitivity	43.33	17.20	19	17633	243806	46424604
Malignant neoplasm progression	41.54	17.20	82	17570	64844	46603566
Product dose omission issue	39.21	17.20	8	17644	168512	46499898
Mucosal inflammation	37.64	17.20	59	17593	38917	46629493
Fall	37.01	17.20	42	17610	329055	46339355
Toxicity to various agents	36.84	17.20	17	17635	211749	46456661
Dyspnoea	36.55	17.20	325	17327	515223	46153187
Condition aggravated	36.37	17.20	24	17628	245028	46423382
Pulpitis dental	36.24	17.20	13	17639	784	46667626
Bone marrow failure	34.50	17.20	49	17603	29620	46638790
Ileus	34.42	17.20	34	17618	14030	46654380
Palmar-plantar erythrodysaesthesia syndrome	31.87	17.20	39	17613	20412	46647998
Cytomegalovirus test positive	31.15	17.20	17	17635	2803	46665607
Weight increased	30.52	17.20	12	17640	164461	46503949
Periodontitis	30.43	17.20	18	17634	3458	46664952
Respiratory depth decreased	29.35	17.20	6	17646	38	46668372
Metastases to liver	28.36	17.20	36	17616	19549	46648861
Breast cancer metastatic	27.93	17.20	30	17622	13648	46654762
Erythema	27.58	17.20	117	17535	142703	46525707
Lymphoedema	27.21	17.20	24	17628	8588	46659822
Drug intolerance	26.83	17.20	11	17641	147038	46521372
Acute myeloid leukaemia recurrent	26.02	17.20	12	17640	1384	46667026
Venous thrombosis limb	25.52	17.20	15	17637	2848	46665562
Sepsis	25.16	17.20	110	17542	135904	46532506
Flushing	25.08	17.20	67	17585	64547	46603863
Lymphocyte count decreased	25.07	17.20	39	17613	25550	46642860
Acute graft versus host disease in skin	24.95	17.20	15	17637	2967	46665443
Off label use	23.59	17.20	233	17419	379608	46288802
Abdominal pain	23.44	17.20	158	17494	229873	46438537
Chronic hepatitis B	23.09	17.20	7	17645	248	46668162
Interstitial lung disease	23.05	17.20	58	17594	53891	46614519
Neuropathy peripheral	22.88	17.20	81	17571	90812	46577598
Hepatic function abnormal	22.64	17.20	44	17608	34377	46634033
Treatment failure	22.53	17.20	4	17648	93083	46575327
Subileus	22.31	17.20	14	17638	2989	46665421
Arthropathy	21.95	17.20	3	17649	84697	46583713
Arthralgia	21.94	17.20	68	17584	364535	46303875
Bone pain	21.72	17.20	52	17600	46838	46621572
Disseminated intravascular coagulation	21.52	17.20	31	17621	18974	46649436
Mitral valve disease	20.80	17.20	12	17640	2200	46666210
Mucosal dryness	20.42	17.20	12	17640	2278	46666132
Musculoskeletal stiffness	20.16	17.20	6	17646	97987	46570423
Hypokalaemia	20.09	17.20	76	17576	87948	46580462
Anaphylactic shock	20.00	17.20	31	17621	20243	46648167
Chest discomfort	19.83	17.20	77	17575	90192	46578218
Maternal exposure during pregnancy	19.82	17.20	7	17645	102542	46565868
Mucosal disorder	19.72	17.20	11	17641	1893	46666517
Therapeutic product effect incomplete	19.71	17.20	3	17649	78150	46590260
Acute interstitial pneumonitis	19.65	17.20	8	17644	682	46667728
Cytopenia	19.42	17.20	19	17633	7749	46660661
Pseudomembranous colitis	19.10	17.20	13	17639	3182	46665228
Peripheral swelling	19.04	17.20	19	17633	158052	46510358
Sinusitis	18.84	17.20	13	17639	129755	46538655
Tumour lysis syndrome	18.65	17.20	18	17634	7218	46661192
Pleural effusion	18.42	17.20	71	17581	82881	46585529
Exposure during pregnancy	18.32	17.20	9	17643	108203	46560207
Fatigue	17.92	17.20	326	17326	608371	46060039
Allergy to chemicals	17.89	17.20	8	17644	859	46667551
Oral candidiasis	17.56	17.20	27	17625	17505	46650905
Ascites	17.40	17.20	41	17611	36543	46631867

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	268.10	16.59	287	13659	106406	29832126
Neutrophil count decreased	127.56	16.59	126	13820	42328	29896204
White blood cell count decreased	88.57	16.59	148	13798	83799	29854733
Drug ineffective	87.96	16.59	25	13921	340362	29598170
Pyrexia	81.92	16.59	311	13635	294178	29644354
Leukopenia	71.57	16.59	108	13838	56051	29882481
Platelet count decreased	70.86	16.59	154	13792	105975	29832557
Neutropenia	62.58	16.59	165	13781	128375	29810157
Vomiting	57.54	16.59	228	13718	219590	29718942
Stomatitis	56.70	16.59	78	13868	37201	29901331
Nausea	52.34	16.59	274	13672	296683	29641849
Mucosal disorder	50.30	16.59	21	13925	1546	29936986
Decreased appetite	42.82	16.59	160	13786	149750	29788782
Interstitial lung disease	42.00	16.59	89	13857	60108	29878424
Disseminated intravascular coagulation	40.85	16.59	51	13895	22120	29916412
Sepsis	40.77	16.59	155	13791	146240	29792292
Diarrhoea	38.34	16.59	276	13670	333827	29604705
Thrombocytopenia	35.62	16.59	142	13804	136902	29801630
Polyneuropathy	35.28	16.59	35	13911	11788	29926744
Fall	34.55	16.59	21	13925	181851	29756681
Antithrombin III decreased	34.22	16.59	11	13935	383	29938149
Colorectal cancer	32.21	16.59	16	13930	1763	29936769
General physical health deterioration	29.60	16.59	108	13838	99836	29838696
Constipation	29.32	16.59	117	13829	112789	29825743
C-reactive protein increased	28.84	16.59	63	13883	43410	29895122
Disease progression	28.63	16.59	92	13854	79782	29858750
Dermatitis acneiform	27.24	16.59	22	13924	5667	29932865
Product dose omission issue	27.00	16.59	5	13941	91626	29846906
Blast cell count increased	26.91	16.59	12	13934	1037	29937495
Hiccups	26.44	16.59	27	13919	9407	29929125
Drug therapeutic incompatibility	25.95	16.59	7	13939	130	29938402
Tumour perforation	24.98	16.59	8	13938	275	29938257
Acute graft versus host disease in skin	24.94	16.59	19	13927	4497	29934035
Anaemia	23.85	16.59	172	13774	207820	29730712
Lymphocyte count decreased	23.32	16.59	36	13910	19019	29919513
Enterocolitis	22.21	16.59	21	13925	6666	29931866
Myocardial infarction	21.82	16.59	16	13930	125609	29812923
Hepatic function abnormal	21.52	16.59	55	13891	41890	29896642
Off label use	21.42	16.59	193	13753	249097	29689435
Non-small cell lung cancer	21.27	16.59	16	13930	3714	29934818
Toxicity to various agents	21.25	16.59	31	13915	177152	29761380
Pneumonia	21.17	16.59	243	13703	334063	29604469
Mucosal inflammation	21.14	16.59	45	13901	30449	29908083
Laryngeal leukoplakia	20.97	16.59	5	13941	55	29938477
Dehydration	20.94	16.59	113	13833	123426	29815106
Peripheral sensory neuropathy	20.50	16.59	19	13927	5882	29932650
Ileus	19.90	16.59	30	13916	15525	29923007
Engraftment syndrome	19.69	16.59	9	13937	824	29937708
Nail bed inflammation	19.58	16.59	6	13940	178	29938354
Palmar-plantar erythrodysaesthesia syndrome	19.48	16.59	29	13917	14841	29923691
Fluid imbalance	18.78	16.59	7	13939	381	29938151
Pulpitis dental	18.47	16.59	7	13939	399	29938133
Arthralgia	18.06	16.59	22	13924	135769	29802763
Hypoalbuminaemia	18.05	16.59	24	13922	11068	29927464
Proteinuria	17.69	16.59	29	13917	16116	29922416
Ileal perforation	17.54	16.59	8	13938	729	29937803
Blood lactate dehydrogenase increased	17.39	16.59	33	13913	20568	29917964
Bone marrow failure	17.34	16.59	41	13905	29744	29908788
Cardiac failure congestive	17.07	16.59	9	13937	84398	29854134

Pharmacologic Action:

Source	Code	Description
ATC	A04AA02	ALIMENTARY TRACT AND METABOLISM ANTIEMETICS AND ANTINAUSEANTS ANTIEMETICS AND ANTINAUSEANTS Serotonin (5HT3) antagonists
FDA MoA	N0000175817	Serotonin 3 Receptor Antagonists
FDA EPC	N0000175818	Serotonin-3 Receptor Antagonist
CHEBI has role	CHEBI:48279	serotonin antagonists
CHEBI has role	CHEBI:50919	antiemetico
MeSH PA	D000932	Antiemetics
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D005765	Gastrointestinal Agents
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D018490	Serotonin Agents
MeSH PA	D012702	Serotonin Antagonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID
Post-Operative Nausea and Vomiting	indication	1488000
Chemotherapy-induced nausea and vomiting	indication	236084000
Prevention of Post-Operative Nausea and Vomiting	indication
Prevention of Radiation-Induced Nausea and Vomiting	indication
Prolonged-Severe Nausea and Vomiting	off-label use
Hypokalemia	contraindication	43339004
Conduction disorder of the heart	contraindication	44808001
Prolonged QT interval	contraindication	111975006
Hypomagnesemia	contraindication	190855004
Congenital long QT syndrome	contraindication	442917000
Doxorubicin Induced Cardiomyopathy	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	13.79	acidic
pKa2	9.5	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
5-hydroxytryptamine receptor 3A	Ion channel	P46098	5HT3A_HUMAN	ANTAGONIST	Ki	8.70	WOMBAT-PK	CHEMBL
Neuronal acetylcholine receptor; alpha4/beta2	Ion channel	P17787 P43681	ACHA4_HUMAN ACHB2_HUMAN		Ki	4.42	CHEMBL
Solute carrier family 22 member 2	Transporter	O15244	S22A2_HUMAN		IC50	5.37	CHEMBL
Neuronal acetylcholine receptor subunit alpha-3	Ion channel	P32297	ACHA3_HUMAN		Ki	4.17	CHEMBL
5-hydroxytryptamine receptor 3B	Ion channel	O95264	5HT3B_HUMAN		Ki	8.80	CHEMBL
Multidrug and toxin extrusion protein 1	Transporter	Q96FL8	S47A1_HUMAN		IC50	5.30	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	5.43	WOMBAT-PK
Serotonin 3 (5-HT3) receptor	Ion channel		5HT3A_RAT 5HT3B_RAT		Ki	9.46	CHEMBL

External reference:

ID	Source
4020855	VUID
N0000179527	NUI
D00677	KEGG_DRUG
107007-99-8	SECONDARY_CAS_RN
4020855	VANDF
4023910	VANDF
C0733443	UMLSCUI
CHEBI:5537	CHEBI
CWB	PDB_CHEM_ID
CHEMBL289469	ChEMBL_ID
CHEMBL1237080	ChEMBL_ID
DB00889	DRUGBANK_ID
D017829	MESH_DESCRIPTOR_UI
5284566	PUBCHEM_CID
2300	IUPHAR_LIGAND_ID
6230	INN_ID
WZG3J2MCOL	UNII
142149	RXNORM
130105	MMSL
157872	MMSL
25895	MMSL
4801	MMSL
d03171	MMSL
003975	NDDF
003976	NDDF
108424001	SNOMEDCT_US
108425000	SNOMEDCT_US
372489005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0054-0143	TABLET	1 mg	ORAL	ANDA	19 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9744	INJECTION	1 mg	INTRAVENOUS	ANDA	25 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9745	INJECTION	1 mg	INTRAVENOUS	ANDA	25 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	16714-221	TABLET, FILM COATED	1 mg	ORAL	ANDA	20 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	16714-221	TABLET, FILM COATED	1 mg	ORAL	ANDA	20 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	17478-546	INJECTION	1 mg	INTRAVENOUS	ANDA	26 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	17478-547	INJECTION	0.10 mg	INTRAVENOUS	ANDA	26 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	42043-390	TABLET, FILM COATED	1 mg	ORAL	ANDA	20 sections
SANCUSO	HUMAN PRESCRIPTION DRUG LABEL	1	42747-726	PATCH	3.10 mg	TRANSDERMAL	NDA	31 sections
SUSTOL	HUMAN PRESCRIPTION DRUG LABEL	1	47426-101	INJECTION	10 mg	SUBCUTANEOUS	NDA	27 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	51991-735	TABLET	1 mg	ORAL	ANDA	21 sections
Sancuso	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5985	PATCH	3.10 mg	TRANSDERMAL	NDA	26 sections
Granisetron Hydrochloride	Human Prescription Drug Label	1	55150-175	INJECTION, SOLUTION	1 mg	INTRAVENOUS	ANDA	24 sections
Granisetron Hydrochloride	Human Prescription Drug Label	1	55150-176	INJECTION, SOLUTION	4 mg	INTRAVENOUS	ANDA	24 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	55648-661	INJECTION	1 mg	INTRAVENOUS	ANDA	16 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	55648-661	INJECTION	1 mg	INTRAVENOUS	ANDA	16 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	55648-662	INJECTION	0.10 mg	INTRAVENOUS	ANDA	16 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	63126-331	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	26 sections
Granisetron	HUMAN PRESCRIPTION DRUG LABEL	1	63323-317	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	25 sections
Granisetron	HUMAN PRESCRIPTION DRUG LABEL	1	63323-318	INJECTION, SOLUTION	1 mg	INTRAVENOUS	ANDA	25 sections
Granisetron	HUMAN PRESCRIPTION DRUG LABEL	1	63323-319	INJECTION, SOLUTION	1 mg	INTRAVENOUS	ANDA	25 sections
Granisetron hydrochloride	Human Prescription Drug Label	1	63850-0005	TABLET, FILM COATED	1 mg	ORAL	ANDA	18 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	64679-661	INJECTION	1 mg	INTRAVENOUS	ANDA	23 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	64679-662	INJECTION	0.10 mg	INTRAVENOUS	ANDA	23 sections
GRANISETRON HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	64679-841	INJECTION	1 mg	INTRAVENOUS	ANDA	23 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	67457-861	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	24 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	67457-863	INJECTION, SOLUTION	1 mg	INTRAVENOUS	ANDA	24 sections
Granisetron Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	67457-864	INJECTION, SOLUTION	1 mg	INTRAVENOUS	ANDA	24 sections
Granisetron Hydrochloride	Human Prescription Drug Label	1	67877-184	TABLET	1 mg	ORAL	ANDA	16 sections