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

Stem definition	Drug id	CAS RN
muscarinic receptors antagonists	2457	242478-37-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: YM-67905 YM-905 solifenacin solifenacin succinate vesicare	A quinuclidine and tetrahydroisoquinoline derivative and selective M3 MUSCARINIC ANTAGONIST. It is used as a UROLOGIC AGENT in the treatment of URINARY INCONTINENCE. Molecular weight: 362.47 Formula: C23H26N2O2 CLOGP: 4.68 LIPINSKI: 0 HAC: 4 HDO: 0 TPSA: 32.78 ALOGS: -3.70 ROTB: 3 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

YM-67905
YM-905
solifenacin
solifenacin succinate
vesicare

A quinuclidine and tetrahydroisoquinoline derivative and selective M3 MUSCARINIC ANTAGONIST. It is used as a UROLOGIC AGENT in the treatment of URINARY INCONTINENCE.

Molecular weight: 362.47
Formula: C23H26N2O2
CLOGP: 4.68
LIPINSKI: 0
HAC: 4
HDO: 0
TPSA: 32.78
ALOGS: -3.70
ROTB: 3

Status: OFP

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

Drug dosage:

Dose	Unit	Route
5	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	12.50 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.30 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	90 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	8.20 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.10 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.02 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	52 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Nov. 19, 2004	FDA	ASTELLAS

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
Dry mouth	486.39	29.27	122	1677	8131	2348155
Off label use	445.37	29.27	193	1606	73405	2282881
Constipation	223.30	29.27	84	1715	21545	2334741
Vision blurred	203.76	29.27	71	1728	14597	2341689
Drug ineffective	201.87	29.27	127	1672	101497	2254789
Urinary retention	194.31	29.27	50	1749	3617	2352669
Dementia	110.54	29.27	30	1769	2651	2353635
Fall	100.54	29.27	62	1737	47037	2309249
Confusional state	95.82	29.27	48	1751	24296	2331990
Dry eye	90.48	29.27	28	1771	3928	2352358
Inappropriate schedule of product administration	75.71	29.27	33	1766	12171	2344115
Dry throat	74.61	29.27	18	1781	990	2355296
Urinary incontinence	72.29	29.27	24	1775	4209	2352077
Malaise	70.30	29.27	53	1746	55532	2300754
Torsade de pointes	69.12	29.27	20	1779	2226	2354060
Wrong technique in product usage process	66.23	29.27	35	1764	19713	2336573
Dizziness	65.59	29.27	52	1747	58613	2297673
Completed suicide	61.39	29.27	34	1765	21000	2335286
Electrocardiogram QT prolonged	61.36	29.27	25	1774	7789	2348497
Acute kidney injury	54.72	29.27	35	1764	28087	2328199
Urinary tract infection	52.72	29.27	35	1764	29907	2326379
Product use in unapproved indication	49.66	29.27	24	1775	11176	2345110
Somnolence	45.09	29.27	29	1770	23456	2332830
Bladder sphincter atony	44.76	29.27	7	1792	34	2356252
Condition aggravated	41.43	29.27	31	1768	31948	2324338
Hallucination	40.82	29.27	19	1780	8129	2348157
Dyspepsia	40.35	29.27	20	1779	9824	2346462
Orthostatic hypotension	40.03	29.27	14	1785	2865	2353421
Hyperkalaemia	39.99	29.27	17	1782	5876	2350410
Hypertonic bladder	39.49	29.27	9	1790	385	2355901
Dysuria	39.30	29.27	15	1784	3926	2352360
Muscular weakness	37.80	29.27	22	1777	14875	2341411
Hypokalaemia	35.99	29.27	19	1780	10635	2345651
Pyelonephritis	35.97	29.27	12	1787	2129	2354157
Cerebral haematoma	35.92	29.27	9	1790	578	2355708
Liver disorder	35.40	29.27	16	1783	6398	2349888
Syncope	35.27	29.27	22	1777	16853	2339433
Oedema peripheral	35.21	29.27	25	1774	23738	2332548
Sinus node dysfunction	34.43	29.27	9	1790	685	2355601
Palpitations	33.25	29.27	21	1778	16435	2339851
Loss of consciousness	33.13	29.27	22	1777	18745	2337541
Abdominal pain	33.10	29.27	28	1771	34346	2321940
Disorientation	32.35	29.27	15	1784	6357	2349929
Pruritus	31.26	29.27	30	1769	43310	2312976
Language disorder	30.95	29.27	7	1792	289	2355997
Hypomagnesaemia	30.09	29.27	11	1788	2553	2353733
Dysphagia	30.09	29.27	18	1781	12787	2343499
Intentional product misuse	29.45	29.27	16	1783	9473	2346813
Mucosal dryness	29.30	29.27	7	1792	368	2355918

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
Off label use	267.77	34.01	107	837	38464	1707373
Dry mouth	224.01	34.01	55	889	3858	1741979
Urinary retention	201.70	34.01	54	890	5341	1740496
Confusional state	149.61	34.01	60	884	21218	1724619
Constipation	136.21	34.01	51	893	14949	1730888
Drug ineffective	102.04	34.01	66	878	63735	1682102
Somnolence	64.31	34.01	31	913	16708	1729129
Parkinson's disease	62.74	34.01	17	927	1725	1744112
Vision blurred	59.64	34.01	24	920	8399	1737438
Fall	57.98	34.01	34	910	27180	1718657
Epilepsy	52.88	34.01	18	926	3941	1741896
Hallucination	46.73	34.01	20	924	8150	1737687
Bladder cancer	46.66	34.01	14	930	2042	1743795
Loss of consciousness	40.86	34.01	22	922	14853	1730984
Hyponatraemia	38.55	34.01	18	926	8982	1736855
Overdose	38.48	34.01	22	922	16679	1729158
Obesity	36.36	34.01	10	934	1069	1744768
Dizziness	34.57	34.01	27	917	34334	1711503

Pharmacologic Action:

Source	Code	Description
ATC	G04BD08	GENITO URINARY SYSTEM AND SEX HORMONES UROLOGICALS UROLOGICALS Drugs for urinary frequency and incontinence
ATC	G04CA53	GENITO URINARY SYSTEM AND SEX HORMONES UROLOGICALS DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY Alpha-adrenoreceptor antagonists
MeSH PA	D018678	Cholinergic Agents
MeSH PA	D018680	Cholinergic Antagonists
MeSH PA	D018727	Muscarinic Antagonists
MeSH PA	D018377	Neurotransmitter Agents
FDA EPC	N0000175700	Cholinergic Muscarinic Antagonist
FDA MoA	N0000000125	Cholinergic Muscarinic Antagonists
MeSH PA	D064804	Urological Agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Urgent desire to urinate	indication	75088002
Urge incontinence of urine	indication	87557004
Bladder muscle dysfunction - overactive	indication	236633002
Increased Urinary Frequency	indication
Torsades de pointes	contraindication	31722008
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Prolonged QT interval	contraindication	111975006
Gastrointestinal obstruction	contraindication	126765001
Disease of liver	contraindication	235856003	DOID:409
Bladder outflow obstruction	contraindication	236645006
Retention of urine	contraindication	267064002
Gastric retention	contraindication	307227006
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Gastrointestinal hypomotility	contraindication	421807004
Congenital long QT syndrome	contraindication	442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.21	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
Muscarinic acetylcholine receptor M3	GPCR	P20309	ACM3_HUMAN	ANTAGONIST	IC50	6.88	CHEMBL	CHEMBL
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN	ANTAGONIST	IC50	6.24	CHEMBL	CHEMBL
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN	ANTAGONIST	Ki	6.80	IUPHAR
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN	ANTAGONIST	Ki	7.20	IUPHAR
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		IC50	7.20	CHEMBL
Muscarinic acetylcholine receptor M1	GPCR		ACM1_RAT		Ki	8	CHEMBL
Muscarinic acetylcholine receptor M3	GPCR		ACM3_RAT		Ki	8	CHEMBL
Muscarinic acetylcholine receptor M2	GPCR		ACM2_RAT		Ki	6.92	CHEMBL

External reference:

ID	Source
D000069464	MESH_DESCRIPTOR_UI
4024390	VUID
N0000022393	NUI
C1099677	UMLSCUI
D01269	KEGG_DRUG
407031006	SNOMEDCT_US
407030007	SNOMEDCT_US
322167	RXNORM
d05413	MMSL
4024390	VANDF
008712	NDDF
A8910SQJ1U	UNII
8155	INN_ID
CHEMBL1734	ChEMBL_ID
CHEMBL1200803	ChEMBL_ID
242478-38-2	SECONDARY_CAS_RN
DB01591	DRUGBANK_ID
CHEBI:135530	CHEBI
154059	PUBCHEM_CID
7483	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-5263	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-5264	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
solifenacin succinate	HUMAN PRESCRIPTION DRUG LABEL	1	27241-037	TABLET, FILM COATED	5 mg	ORAL	ANDA	16 sections
solifenacin succinate	HUMAN PRESCRIPTION DRUG LABEL	1	27241-038	TABLET, FILM COATED	10 mg	ORAL	ANDA	16 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	29300-328	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	29300-329	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	35561-285	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	35561-286	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	46708-192	TABLET, COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	46708-193	TABLET, COATED	10 mg	ORAL	ANDA	17 sections
solifenacin succinate	HUMAN PRESCRIPTION DRUG LABEL	1	48792-7909	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
solifenacin succinate	HUMAN PRESCRIPTION DRUG LABEL	1	48792-7910	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
SOLIFENACIN SUCCINATE	HUMAN PRESCRIPTION DRUG LABEL	1	50228-427	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
SOLIFENACIN SUCCINATE	HUMAN PRESCRIPTION DRUG LABEL	1	50228-428	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	51248-150	TABLET, FILM COATED	5 mg	ORAL	NDA	17 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	51248-151	TABLET, FILM COATED	10 mg	ORAL	NDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	51407-227	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	51407-228	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
SOLIFENACIN SUCCINATE	HUMAN PRESCRIPTION DRUG LABEL	1	51407-254	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
SOLIFENACIN SUCCINATE	HUMAN PRESCRIPTION DRUG LABEL	1	51407-255	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	54868-4705	TABLET, FILM COATED	10 mg	ORAL	NDA	16 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5398	TABLET, FILM COATED	5 mg	ORAL	NDA	16 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	55154-3877	TABLET, FILM COATED	5 mg	ORAL	NDA	17 sections
VESIcare	HUMAN PRESCRIPTION DRUG LABEL	1	55154-3878	TABLET, FILM COATED	10 mg	ORAL	NDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	60505-4702	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	60505-4703	TABLET, FILM COATED	10 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	60687-499	TABLET, COATED	5 mg	ORAL	ANDA	18 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	62332-192	TABLET, COATED	5 mg	ORAL	ANDA	17 sections
Solifenacin Succinate	HUMAN PRESCRIPTION DRUG LABEL	1	62332-193	TABLET, COATED	10 mg	ORAL	ANDA	17 sections
solifenacin succinate	HUMAN PRESCRIPTION DRUG LABEL	1	64380-941	TABLET, FILM COATED	5 mg	ORAL	ANDA	17 sections