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

Stem definition	Drug id	CAS RN
	2705	124937-51-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: tolterodine tolterodine tartrate (+)-Tolterodine (R)-Tolterodine	An ANTIMUSCARINIC AGENT selective for the MUSCARINIC RECEPTORS of the BLADDER that is used in the treatment of URINARY INCONTINENCE and URINARY URGE INCONTINENCE. Molecular weight: 325.50 Formula: C22H31NO CLOGP: 5.24 LIPINSKI: 1 HAC: 2 HDO: 1 TPSA: 23.47 ALOGS: -4.78 ROTB: 7 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

tolterodine
tolterodine tartrate
(+)-Tolterodine
(R)-Tolterodine

An ANTIMUSCARINIC AGENT selective for the MUSCARINIC RECEPTORS of the BLADDER that is used in the treatment of URINARY INCONTINENCE and URINARY URGE INCONTINENCE.

Molecular weight: 325.50
Formula: C22H31NO
CLOGP: 5.24
LIPINSKI: 1
HAC: 2
HDO: 1
TPSA: 23.47
ALOGS: -4.78
ROTB: 7

Status: OFP

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

Drug dosage:

Dose	Unit	Route
4	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	12 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	1 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	24.58 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.50 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	8.40 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.04 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	2.40 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
March 25, 1998	FDA	PHARMACIA AND UPJOHN

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
Drug ineffective	374.64	28.68	156	826	101468	2255635
Dry mouth	365.61	28.68	86	896	8167	2348936
Drug hypersensitivity	319.01	28.68	113	869	46530	2310573
Urinary incontinence	149.88	28.68	37	945	4196	2352907
Urinary retention	144.80	28.68	35	947	3632	2353471
Pollakiuria	143.97	28.68	35	947	3721	2353382
Constipation	111.56	28.68	43	939	21586	2335517
Nocturia	99.65	28.68	20	962	870	2356233
Urinary tract infection	91.56	28.68	41	941	29901	2327202
Fall	90.92	28.68	47	935	47052	2310051
Hypertonic bladder	82.59	28.68	15	967	379	2356724
Drug interaction	73.64	28.68	35	947	29128	2327975
Condition aggravated	67.60	28.68	34	948	31945	2325158
Dizziness	65.56	28.68	41	941	58624	2298479
Hallucination, auditory	61.78	28.68	16	966	2176	2354927
Confusional state	60.73	28.68	29	953	24315	2332788
Oesophagitis	58.27	28.68	15	967	1991	2355112
Paranoia	57.54	28.68	15	967	2092	2355011
Dry eye	52.43	28.68	16	966	3940	2353163
Blood cholesterol increased	52.02	28.68	17	965	5224	2351879
Haemoglobin abnormal	50.91	28.68	11	971	684	2356419
Neutrophil count abnormal	49.73	28.68	10	972	437	2356666
Hypertension	48.84	28.68	26	956	27335	2329768
Incontinence	47.77	28.68	12	970	1442	2355661
Bladder disorder	45.68	28.68	11	971	1110	2355993
White blood cell count abnormal	45.05	28.68	10	972	705	2356398
Vision blurred	44.38	28.68	20	962	14648	2342455
Pain in extremity	43.07	28.68	28	954	42512	2314591
Therapeutic product effect decreased	40.06	28.68	17	965	10772	2346331
Macular degeneration	39.71	28.68	10	972	1213	2355890
Depressed level of consciousness	38.60	28.68	15	967	7589	2349514
Arthritis	37.98	28.68	16	966	9952	2347151
Abdominal pain upper	36.60	28.68	20	962	22080	2335023
Gastrooesophageal reflux disease	36.00	28.68	15	967	9080	2348023
Micturition urgency	34.55	28.68	9	973	1247	2355856
Dysphagia	34.14	28.68	16	966	12789	2344314
Psychotic disorder	33.93	28.68	12	970	4667	2352436
Insomnia	33.72	28.68	20	962	25767	2331336
Vulvovaginal dryness	32.47	28.68	7	975	430	2356673
Headache	31.17	28.68	30	952	80149	2276954
Weight decreased	29.46	28.68	19	963	28352	2328751

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
Drug ineffective	106.48	35.81	48	300	63753	1682680
Urinary retention	104.24	35.81	26	322	5369	1741064
Dry mouth	101.91	35.81	24	324	3889	1742544
Nocturia	56.98	35.81	12	336	1149	1745284
Pollakiuria	55.69	35.81	14	334	2932	1743501
Urinary incontinence	41.88	35.81	11	337	2725	1743708
Dysuria	38.68	35.81	11	337	3661	1742772

Pharmacologic Action:

Source	Code	Description
ATC	G04BD07	GENITO URINARY SYSTEM AND SEX HORMONES UROLOGICALS UROLOGICALS Drugs for urinary frequency and incontinence
FDA EPC	N0000175700	Cholinergic Muscarinic Antagonist
FDA MoA	N0000000125	Cholinergic Muscarinic Antagonists
CHEBI has role	CHEBI:48876	muscarinic antagonist
CHEBI has role	CHEBI:53784	antispasmodic drug
CHEBI has role	CHEBI:51371	muscle relaxant
MeSH PA	D018678	Cholinergic Agents
MeSH PA	D018680	Cholinergic Antagonists
MeSH PA	D018727	Muscarinic Antagonists
MeSH PA	D018377	Neurotransmitter Agents
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
Dementia	contraindication	52448006
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Myasthenia gravis	contraindication	91637004	DOID:437
Prolonged QT interval	contraindication	111975006
Bladder outflow obstruction	contraindication	236645006
Pyloric obstruction	contraindication	244815007
Retention of urine	contraindication	267064002
Gastric retention	contraindication	307227006
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Gastrointestinal hypomotility	contraindication	421807004
Poor metabolizer due to cytochrome p450 CYP2D6 variant	contraindication	423629005
Congenital long QT syndrome	contraindication	442917000
Aggravated Glaucoma	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.83	acidic
pKa2	9.14	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	Ki	8.49	CHEMBL	CHEMBL
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN	ANTAGONIST	Ki	8.57	CHEMBL	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	7.77	CHEMBL
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN		Ki	8.51	CHEMBL
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	8.66	CHEMBL
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	8.85	CHEMBL
Muscarinic acetylcholine receptor M3	GPCR		ACM3_RAT		Ki	8.15	CHEMBL
Muscarinic acetylcholine receptor M2	GPCR		ACM2_RAT		Ki	8.16	CHEMBL

External reference:

ID	Source
D000068737	MESH_DESCRIPTOR_UI
4024113	VUID
N0000022118	NUI
C0388753	UMLSCUI
D00646	KEGG_DRUG
5T619TQR3R	UNII
124937-52-6	SECONDARY_CAS_RN
109113000	SNOMEDCT_US
4024113	VANDF
007444	NDDF
d04294	MMSL
119565	RXNORM
372570008	SNOMEDCT_US
CHEMBL1382	ChEMBL_ID
DB01036	DRUGBANK_ID
CHEBI:9622	CHEBI
6768	INN_ID
443879	PUBCHEM_CID
CHEMBL1722209	ChEMBL_ID
360	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Detrol	HUMAN PRESCRIPTION DRUG LABEL	1	0009-4541	TABLET, FILM COATED	1 mg	ORAL	NDA	14 sections
Detrol	HUMAN PRESCRIPTION DRUG LABEL	1	0009-4544	TABLET, FILM COATED	2 mg	ORAL	NDA	14 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	0009-5190	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	NDA	18 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	0009-5191	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	NDA	18 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0010	TABLET, FILM COATED	1 mg	ORAL	ANDA	13 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0018	TABLET, FILM COATED	2 mg	ORAL	ANDA	13 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7163	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7164	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-3402	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-3404	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	17 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6592	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	16 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6593	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	16 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	13668-189	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	16 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	13668-190	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	16 sections
DETROL	HUMAN PRESCRIPTION DRUG LABEL	1	16590-959	TABLET, FILM COATED	2 mg	ORAL	NDA	13 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	31722-607	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	31722-608	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	17 sections
Tolterodine tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	33342-097	TABLET, FILM COATED	1 mg	ORAL	ANDA	13 sections
Tolterodine tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	33342-098	TABLET, FILM COATED	2 mg	ORAL	ANDA	13 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43353-346	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	19 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43975-322	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43975-323	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	50090-3475	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	17 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	51079-197	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	18 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	51079-198	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	18 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	54868-4514	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	NDA	17 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5126	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	NDA	17 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	55289-132	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	NDA	18 sections
Tolterodine Tartrate Extended Release	HUMAN PRESCRIPTION DRUG LABEL	1	59762-0047	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	NDA	18 sections
Tolterodine Tartrate Extended Release	HUMAN PRESCRIPTION DRUG LABEL	1	59762-0048	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	NDA	18 sections