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

Stem definitionDrug idCAS RN
2705 124937-51-5

Description:

MoleculeDescription

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:

DoseUnitRoute
4 mg O

ADMET properties:

PropertyValueReference
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 ┬ÁM/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:

DateAgencyCompanyOrphan
March 25, 1998 FDA PHARMACIA AND UPJOHN

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Muscarinic acetylcholine receptor M3 GPCR ANTAGONIST Ki 8.49 CHEMBL CHEMBL
Muscarinic acetylcholine receptor M2 GPCR ANTAGONIST Ki 8.57 CHEMBL CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 7.77 CHEMBL
Muscarinic acetylcholine receptor M4 GPCR Ki 8.51 CHEMBL
Muscarinic acetylcholine receptor M5 GPCR Ki 8.66 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 8.85 CHEMBL
Muscarinic acetylcholine receptor M3 GPCR Ki 8.15 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR Ki 8.16 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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