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
Sensitivity to weather change	92.75	11.33	47	21441	5469	46659105
Urinary tract infection	92.60	11.33	266	21222	220000	46444574
Urinary incontinence	83.28	11.33	83	21405	28447	46636127
Dry mouth	83.17	11.33	114	21374	54812	46609762
Multiple sclerosis relapse	70.77	11.33	92	21396	42033	46622541
Pollakiuria	67.91	11.33	69	21419	24192	46640382
Multiple sclerosis	66.66	11.33	69	21419	24722	46639852
Hypertonic bladder	57.63	11.33	28	21460	2976	46661598
Fall	54.95	11.33	297	21191	328800	46335774
Bladder disorder	49.02	11.33	34	21454	7044	46657530
Antinuclear antibody negative	44.37	11.33	12	21476	228	46664346
Coombs positive haemolytic anaemia	42.86	11.33	13	21475	377	46664197
Nocturia	41.91	11.33	31	21457	7101	46657473
Herpes simplex reactivation	39.56	11.33	12	21476	348	46664226
Maternal exposure during pregnancy	33.37	11.33	4	21484	102545	46562029
Exposure during pregnancy	33.36	11.33	5	21483	108207	46556367
Micturition urgency	31.03	11.33	27	21461	7790	46656784
Stress urinary incontinence	29.76	11.33	16	21472	2100	46662474
Urinary retention	29.21	11.33	47	21441	26014	46638560
Bladder spasm	29.02	11.33	14	21474	1465	46663109
Gastritis haemorrhagic	27.38	11.33	13	21475	1313	46663261
Balance disorder	27.07	11.33	78	21410	64443	46600131
Gastrooesophageal reflux disease	25.71	11.33	84	21404	74260	46590314
Completed suicide	25.52	11.33	18	21470	145902	46518672
Cerebrovascular accident	24.69	11.33	102	21386	100937	46563637
Off label use	24.58	11.33	91	21397	379750	46284824
Antiphospholipid syndrome	24.23	11.33	13	21475	1699	46662875
Treatment failure	23.19	11.33	7	21481	93080	46571494
Hyperlipidaemia	22.95	11.33	35	21453	18504	46646070
Transient ischaemic attack	22.86	11.33	50	21438	34853	46629721
Complex regional pain syndrome	21.95	11.33	13	21475	2053	46662521
Toxicity to various agents	21.92	11.33	40	21448	211726	46452848
Hypothyroidism	21.80	11.33	46	21442	31292	46633282
Oesophagitis	20.14	11.33	28	21460	13623	46650951
Confusional state	19.98	11.33	134	21354	159758	46504816
Contraindicated product administered	19.94	11.33	6	21482	79941	46584633
Coronary artery disease	19.49	11.33	46	21442	33706	46630868
Drug abuse	19.38	11.33	3	21485	63405	46601169
Incontinence	18.87	11.33	23	21465	9839	46654735
Dizziness	18.33	11.33	238	21250	340176	46324398
Depression	18.03	11.33	137	21351	169967	46494607
Anxiety disorder	17.85	11.33	14	21474	3497	46661077
Therapy non-responder	17.50	11.33	50	21438	41102	46623472
Urge incontinence	17.42	11.33	8	21480	749	46663825
Hallucination, auditory	17.29	11.33	23	21465	10733	46653841
White blood cell count abnormal	16.98	11.33	16	21472	5116	46659458
Neutropenia	16.72	11.33	25	21463	143179	46521395
Constipation	16.68	11.33	137	21351	173960	46490614
Secondary progressive multiple sclerosis	16.53	11.33	9	21479	1211	46663363
Iliac artery occlusion	16.45	11.33	5	21483	146	46664428
Blood cholesterol increased	16.42	11.33	48	21440	39965	46624609
Paranoia	16.03	11.33	22	21466	10575	46653999
Mental status changes	15.93	11.33	46	21442	38042	46626532
Perforation	15.40	11.33	8	21480	979	46663595
Gait disturbance	15.39	11.33	117	21371	145146	46519428
Neutrophil count abnormal	15.19	11.33	11	21477	2439	46662135
Barrett's oesophagus	15.09	11.33	7	21481	671	46663903
Death	14.36	11.33	93	21395	335455	46329119
Aphonia	14.35	11.33	18	21470	7927	46656647
Malignant neoplasm progression	14.26	11.33	6	21482	64920	46599654
Drug hypersensitivity	14.18	11.33	173	21315	243652	46420922
Febrile neutropenia	13.69	11.33	14	21474	94613	46569961
Dysphagia	13.66	11.33	71	21417	77241	46587333
Infusion related reaction	13.51	11.33	16	21472	101192	46563382
Drug intolerance	13.31	11.33	30	21458	147019	46517555
Haemoglobin abnormal	13.29	11.33	13	21475	4350	46660224
Product complaint	12.45	11.33	21	21467	12080	46652494
Cystitis	12.22	11.33	45	21443	42196	46622378
Rheumatoid arthritis	12.18	11.33	63	21425	240152	46424422
Increased appetite	11.85	11.33	17	21471	8510	46656064
Dementia	11.66	11.33	23	21465	14907	46649667
Osteonecrosis	11.65	11.33	32	21456	25712	46638862
Neurogenic bladder	11.45	11.33	10	21478	2900	46661674
Haemoglobin	11.42	11.33	4	21484	184	46664390

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
Seronegative arthritis	55.96	14.78	16	6631	797	29945034
Dry mouth	54.10	14.78	43	6604	22807	29923024
Pollakiuria	53.82	14.78	38	6609	16868	29928963
Lipoma	46.49	14.78	16	6631	1467	29944364
Urinary incontinence	44.70	14.78	34	6613	16906	29928925
Fall	42.04	14.78	111	6536	181761	29764070
Urinary retention	38.86	14.78	42	6605	32875	29912956
Balance disorder	38.67	14.78	44	6603	36449	29909382
Prostatic specific antigen increased	35.94	14.78	26	6621	11978	29933853
Micturition urgency	35.43	14.78	18	6629	4389	29941442
Inflammatory marker increased	34.62	14.78	16	6631	3172	29942659
Musculoskeletal discomfort	26.88	14.78	17	6630	6283	29939548
Multiple sclerosis	22.34	14.78	16	6631	7251	29938580
Urinary tract infection	22.33	14.78	50	6597	73609	29872222
Hypertonic bladder	21.91	14.78	8	6639	871	29944960
Bladder disorder	21.01	14.78	11	6636	2852	29942979
Nocturia	20.43	14.78	16	6631	8296	29937535
Failure to thrive	18.71	14.78	15	6632	8039	29937792
Cerebrovascular accident	18.25	14.78	50	6597	83427	29862404
Rectal tenesmus	17.53	14.78	6	6641	541	29945290
Confusional state	16.23	14.78	66	6581	134768	29811063
Blood pressure systolic increased	15.62	14.78	18	6629	15092	29930739
Muscular weakness	14.78	14.78	39	6608	63606	29882225

Pharmacologic Action:

Source	Code	Description
ATC	G04BD07	GENITO URINARY SYSTEM AND SEX HORMONES UROLOGICALS UROLOGICALS Drugs for urinary frequency and incontinence
FDA MoA	N0000000125	Cholinergic Muscarinic Antagonists
FDA EPC	N0000175700	Cholinergic Muscarinic Antagonist
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
CHEBI has role	CHEBI:48876	antimuskarinika
CHEBI has role	CHEBI:51371	muscle relaxants
CHEBI has role	CHEBI:53784	antispasmodics

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
4024113	VUID
N0000022118	NUI
D00646	KEGG_DRUG
124937-52-6	SECONDARY_CAS_RN
4021103	VANDF
4024113	VANDF
C0388753	UMLSCUI
CHEBI:9622	CHEBI
443879	PUBCHEM_CID
DB01036	DRUGBANK_ID
CHEMBL1382	ChEMBL_ID
CHEMBL1722209	ChEMBL_ID
D000068737	MESH_DESCRIPTOR_UI
6768	INN_ID
WHE7A56U7K	UNII
360	IUPHAR_LIGAND_ID
119565	RXNORM
191519	MMSL
5600	MMSL
d04294	MMSL
007444	NDDF
007445	NDDF
109113000	SNOMEDCT_US
372570008	SNOMEDCT_US
386971005	SNOMEDCT_US

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	25 sections
Detrol	HUMAN PRESCRIPTION DRUG LABEL	1	0009-4544	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	0009-5190	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	NDA	29 sections
Detrol LA	HUMAN PRESCRIPTION DRUG LABEL	1	0009-5191	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	NDA	29 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0010	TABLET, FILM COATED	1 mg	ORAL	ANDA	25 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0018	TABLET, FILM COATED	2 mg	ORAL	ANDA	25 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7163	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	26 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7164	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	26 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-3402	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	27 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-3404	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	27 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6592	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	20 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6593	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	20 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	10135-706	TABLET, EXTENDED RELEASE	1 mg	ORAL	ANDA	22 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	10135-707	TABLET, EXTENDED RELEASE	2 mg	ORAL	ANDA	22 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	13668-189	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	20 sections
TOLTERODINE TARTRATE	HUMAN PRESCRIPTION DRUG LABEL	1	13668-190	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	20 sections
Tolterodine Tartrate	Human Prescription Drug Label	1	16571-126	TABLET, FILM COATED	1 mg	ORAL	ANDA	21 sections
Tolterodine Tartrate	Human Prescription Drug Label	1	16571-127	TABLET, FILM COATED	2 mg	ORAL	ANDA	21 sections
DETROL	HUMAN PRESCRIPTION DRUG LABEL	1	16590-959	TABLET, FILM COATED	2 mg	ORAL	NDA	23 sections
Tolterodine tartrate	Human Prescription Drug Label	1	27241-191	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	26 sections
Tolterodine tartrate	Human Prescription Drug Label	1	27241-192	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	26 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	29300-239	TABLET	1 mg	ORAL	ANDA	20 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	29300-240	TABLET	2 mg	ORAL	ANDA	20 sections
Tolterodine Tartrate	Human Prescription Drug Label	1	31722-607	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	26 sections
Tolterodine Tartrate	Human Prescription Drug Label	1	31722-608	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	26 sections
Tolterodine tartrate	Human Prescription Drug Label	1	33342-097	TABLET, FILM COATED	1 mg	ORAL	ANDA	22 sections
Tolterodine tartrate	Human Prescription Drug Label	1	33342-098	TABLET, FILM COATED	2 mg	ORAL	ANDA	22 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43353-346	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	27 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43975-322	CAPSULE, EXTENDED RELEASE	2 mg	ORAL	ANDA	25 sections
Tolterodine Tartrate	HUMAN PRESCRIPTION DRUG LABEL	1	43975-323	CAPSULE, EXTENDED RELEASE	4 mg	ORAL	ANDA	25 sections