DESFESOTERODINE FUMARATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H31NO2.C4H4O4
Molecular Weight	457.5592
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CC(C)N(CC[C@H](C1=CC=CC=C1)C2=CC(CO)=CC=C2O)C(C)C

InChI

InChIKey=CFLJDPGMBAKCIK-BOQYJDHWSA-N

InChI=1S/C22H31NO2.C4H4O4/c1-16(2)23(17(3)4)13-12-20(19-8-6-5-7-9-19)21-14-18(15-24)10-11-22(21)25;5-3(6)1-2-4(7)8/h5-11,14,16-17,20,24-25H,12-13,15H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t20-;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19835561https://www.ncbi.nlm.nih.gov/pubmed/19835561 | DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F | https://www.ncbi.nlm.nih.gov/pubmed/9353847
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18279452

Desfesoterodine is an active metabolite of antimuscarinic drugs for the treatment of overactive bladder fesoterodine and tolterodine. In contrast to the cytochrome P450 (CYP) 2D6-mediated metabolism of tolterodine, desfesoterodine formation from fesoterodine occurs via ubiquitous nonspecific esterases. Serum levels of the desfesoterodine in humans are generally comparable to those of tolterodine following oral administration of the parent compound. The pharmacological in vitro and in vivo profiles of desfesoterodine are almost identical to those of tolterodin. The potent antimuscarinic action of desfesoterodine on the urinary bladder was confirmed in the in vivo studies and, like tolterodine, desfesoterodine was significantly more potent in inhibiting bladder contractions than salivation in the anaesthetised cat. Desfesoterodine is more potent than tolterodine in vivo. The apparent difference in potency in vivo might be explained by the degree of serum protein binding of the two compounds. The fraction of unbound drug in serum is larger for desfesoterodine than for tolterodine. Desfesoterodine may contribute to the therapeutical action of tolterodine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2778	2.3 nM [Ki]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2778	2.0 nM [Ki]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2778	2.5 nM [Ki]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2778	2.8 nM [Ki]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2778	2.9 nM [Ki]
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2778	8.0 null [pKi]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2778	7.7 null [pKi]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2778	7.4 null [pKi]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2778	7.3 null [pKi]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2778	7.5 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Urinary incontinence 14 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F https://www.ncbi.nlm.nih.gov/pubmed/9353847	Primary	Preclinical	Unknown Approved Use Unknown
Partial urethral obstruction 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19888972 https://www.ncbi.nlm.nih.gov/pubmed/20639056	Primary	Preclinical	Unknown Approved Use Unknown
Overactive bladder 38 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	Palliative	Approved 8429	TOVIAZ Approved Use Toviaz is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Launch Date 2008
Overactive bladder 38 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022030lbl.pdf	Primary	Approved 8429	TOVIAZ Approved Use Toviaz® is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Toviaz is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Launch Date 2008

C_max

Value	Dose	Co-administered	Analyte	Population
1.89 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.31 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00928070	unhealthy, adult n = 281 Health Status: unhealthy Condition: Overactive Bladder Age Group: adult Population Size: 281 Sources: https://clinicaltrials.gov/ct2/show/NCT00928070	Other AEs: Coronary artery occlusion, Influenza... Other AEs: Coronary artery occlusion (serious, 1 patient) Influenza (serious, 1 patient) Urosepsis (serious, 1 patient) Fall (serious, 1 patient) Femur fracture (serious, 1 patient) Haemarthrosis (serious, 1 patient) Muscular weakness (serious, 1 patient) Osteoarthritis (serious, 1 patient) Bradycardia (below serious, 1 patient) Cardiac failure congestive (below serious, 1 patient) Ventricular extrasystoles (below serious, 1 patient) Dry eye (below serious, 4 patients) Discharge eye (below serious, 1 patient) Eye haemorrhage (below serious, 1 patient) Eye oedema (below serious, 1 patient) Eye swelling (below serious, 1 patient) Vitreous floaters (below serious, 1 patient) Abdominal discomfort (below serious, 1 patient) Abdominal distension (below serious, 2 patients) Constipation (below serious, 31 patient) Diarrhoea (below serious, 8 patients) Dry mouth (below serious, 66 patients) Dyspepsia (below serious, 7 patients) Faecal incontinence (below serious, 1 patient) Flatulence (below serious, 2 patients) Gastrooesophageal reflux disease (below serious, 3 patients) Haemorrhoids (below serious, 1 patient) Hiatus hernia (below serious, 1 patient) Nausea (below serious, 5 patients) Tongue dry (below serious, 1 patient) Fatigue (below serious, 8 patients) Local swelling (below serious, 1 patient) Oedema (below serious, 1 patient) Therapeutic response unexpected (below serious, 1 patient) Candidiasis (below serious, 1 patient) Diverticulitis (below serious, 1 patient) Herpes simplex (below serious, 1 patient) Herpes zoster ophthalmic (below serious, 1 patient) Oral herpes (below serious, 1 patient) Pneumonia viral (below serious, 1 patient) Sinusitis (below serious, 5 patients) Tinea pedis (below serious, 1 patient) Tooth abscess (below serious, 1 patient) Vulvovaginal candidiasis (below serious, 1 patient) Arthropod bite (below serious, 1 patient) Contusion (below serious, 3 patients) Laceration (below serious, 1 patient) Post procedural haematoma (below serious, 1 patient) Skeletal injury (below serious, 2 patients) Blood glucose increased (below serious, 1 patient) Blood pressure increased (below serious, 2 patients) Blood uric acid increased (below serious, 1 patient) International normalised ratio increased (below serious, 1 patient) Residual urine volume increased (below serious, 1 patient) Weight increased (below serious, 1 patient) Gout (below serious, 2 patients) Type 2 diabetes mellitus (below serious, 1 patient) Back pain (below serious, 4 patients) Bursitis (below serious, 1 patient) Intervertebral disc degeneration (below serious, 1 patient) Musculoskeletal chest pain (below serious, 1 patient) Musculoskeletal pain (below serious, 2 patients) Osteoporosis (below serious, 1 patient) Trigger finger (below serious, 1 patient) Skin cancer (below serious, 1 patient) Diabetic neuropathy (below serious, 1 patient) Dizziness (below serious, 3 patients) Headache (below serious, 7 patients) Hypersomnia (below serious, 1 patient) Memory impairment (below serious, 2 patients) Migraine (below serious, 1 patient) Sinus headache (below serious, 1 patient) Tremor (below serious, 1 patient) Confusional state (below serious, 1 patient) Depression (below serious, 1 patient) Sleep disorder (below serious, 1 patient) Dysuria (below serious, 4 patients) Nephrolithiasis (below serious, 1 patient) Urinary hesitation (below serious, 1 patient) Urinary retention (below serious, 9 patients) Urine odour abnormal (below serious, 1 patient) Haemorrhage vaginal (below serious, 1 patient) Asthma (below serious, 1 patient) Bronchospasm (below serious, 1 patient) Chronic obstructive pulmonary disease (below serious, 2 patients) Cough (below serious, 7 patients) Dry throat (below serious, 5 patients) Dysphonia (below serious, 1 patient) Dyspnoea exertional (below serious, 1 patient) Epistaxis (below serious, 1 patient) Nasal dryness (below serious, 1 patient) Oropharyngeal pain (below serious, 2 patients) Allergic rhinitis (below serious, 1 patient) Sinus congestion (below serious, 2 patients) Blister (below serious, 1 patient) Ingrowing nail (below serious, 1 patient) Onychoclasis (below serious, 1 patient) Pruritus (below serious, 2 patients) Generalised pruritus (below serious, 1 patient) Urticaria (below serious, 1 patient) Flushing (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00928070
28 mg 1 times / day multiple, oral Highest studied dose Dose: 28 mg, 1 times / day Route: oral Route: multiple Dose: 28 mg, 1 times / day Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18	Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4	unhealthy n = 785 Health Status: unhealthy Condition: Overactive bladder Population Size: 785 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (0.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1	Disc. AE: Face angioedema, Lip angioedema... AEs leading to discontinuation/dose reduction: Face angioedema Lip angioedema Oedema tongue Angioedema of larynx Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00832650	healthy n = 25 Health Status: healthy Sex: F Population Size: 25 Sources: https://clinicaltrials.gov/ct2/show/NCT00832650	Other AEs: Dry eye, Abdominal pain... Other AEs: Dry eye (below serious, 1 patient) Abdominal pain (below serious, 2 patients) Constipation (below serious, 1 patient) Diarrhoea (below serious, 2 patients) Dry mouth (below serious, 13 patients) Dyschezia (below serious, 1 patient) Oedema peripheral (below serious, 1 patient) Nasopharyngitis (below serious, 2 patients) Headache (below serious, 12 patients) Pollakiuria (below serious, 1 patient) Dry throat (below serious, 1 patient) Oropharyngeal pain (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00832650
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00862745	unhealthy n = 322 Health Status: unhealthy Condition: Urge Urinary Incontinence Sex: F Population Size: 322 Sources: https://clinicaltrials.gov/ct2/show/NCT00862745	Other AEs: Myocardial infarction, Embolus pulmonary... Other AEs: Myocardial infarction (serious, 1 patient) Embolus pulmonary (serious, 1 patient) Breast cancer (serious, 1 patient) Colitis (serious, 1 patient) Constipation (below serious, 24 patients) Headache (below serious, 19 patients) Cold (below serious, 21 patient) Urinary tract infection (below serious, 17 patients) Cough (below serious, 10 patients) Nausea (below serious, 10 patients) Dyspepsia (below serious, 9 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00862745
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00546637	unhealthy n = 471 Health Status: unhealthy Condition: Overactive Bladder Sex: M Population Size: 471 Sources: https://clinicaltrials.gov/ct2/show/NCT00546637	Other AEs: Myocardial infarction, Colitis ulcerative... Other AEs: Myocardial infarction (serious, 1 patient) Colitis ulcerative (serious, 1 patient) Cellulitis staphylococcal (serious, 1 patient) Genitourinary tract infection (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Lung neoplasm malignant (serious, 1 patient) Transitional cell carcinoma (serious, 1 patient) Dysuria (serious, 1 patient) Colic renal (serious, 1 patient) Testicular torsion (serious, 1 patient) Orthostatic hypotension (serious, 1 patient) Abdominal pain (below serious, 6 patients) Constipation (below serious, 31 patient) Diarrhoea (below serious, 9 patients) Dry mouth (below serious, 100 patients) Dyspepsia (below serious, 9 patients) Gastritis (below serious, 5 patients) Nausea (below serious, 6 patients) Influenza (below serious, 6 patients) Nasopharyngitis (below serious, 5 patients) Sinusitis (below serious, 5 patients) Headache (below serious, 15 patients) Insomnia (below serious, 9 patients) Dysuria (below serious, 15 patients) Urinary retention (below serious, 11 patient) Erectile dysfunction (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00546637
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00444925	unhealthy n = 679 Health Status: unhealthy Condition: Overactive Bladder Population Size: 679 Sources: https://clinicaltrials.gov/ct2/show/NCT00444925	Other AEs: Anaemia iron deficiency, Hypertensive heart disease... Other AEs: Anaemia iron deficiency (serious, 1 patient) Hypertensive heart disease (serious, 1 patient) Myocardial ischaemia (serious, 1 patient) Abdominal pain (serious, 1 patient) Appendicitis perforated (serious, 1 patient) Rectal haemorrhage (serious, 1 patient) Bronchiectasis (serious, 1 patient) Traumatic brain injury (serious, 1 patient) Upper limb fracture (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Hepatic neoplasm malignant (serious, 1 patient) Prostate cancer (serious, 1 patient) Haemorrhage intracranial (serious, 1 patient) Suicidal behaviour (serious, 1 patient) Urinary incontinence (serious, 1 patient) Haemorrhage uterine (serious, 1 patient) Vision blurred (below serious, 12 patients) Abdominal pain (below serious, 10 patients) Abdominal pain upper (below serious, 9 patients) Constipation (below serious, 37 patients) Diarrhoea (below serious, 14 patients) Dry mouth (below serious, 189 patients) Dyspepsia (below serious, 12 patients) Vomiting (below serious, 7 patients) Fatigue (below serious, 12 patients) Urinary tract infection (below serious, 15 patients) Dizziness (below serious, 8 patients) Headache (below serious, 38 patients) Dysuria (below serious, 4 patients) Cough (below serious, 8 patients) Hypertension (below serious, 8 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00444925
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00911937	unhealthy n = 463 Health Status: unhealthy Condition: Overactive Bladder Population Size: 463 Sources: https://clinicaltrials.gov/ct2/show/NCT00911937	Other AEs: Septic arthritis staphylococcal, Ankle fracture... Other AEs: Septic arthritis staphylococcal (serious, 1 patient) Ankle fracture (serious, 1 patient) Fall (serious, 1 patient) Hip fracture (serious, 1 patient) Tibia fracture (serious, 1 patient) Diabetic ketoacidosis (serious, 1 patient) Lymphoma (serious, 1 patient) Renal failure acute (serious, 1 patient) Otorrhoea (below serious, 1 patient) Hypothyroidism (below serious, 1 patient) Dry eye (below serious, 9 patients) Abdominal pain (below serious, 4 patients) Abdominal pain upper (below serious, 2 patients) Colitis (below serious, 1 patient) Constipation (below serious, 15 patients) Dry mouth (below serious, 98 patients) Dyspepsia (below serious, 5 patients) Dysphagia (below serious, 1 patient) Gastritis (below serious, 1 patient) Gastrooesophageal reflux disease (below serious, 2 patients) Haemorrhoids (below serious, 1 patient) Lip dry (below serious, 1 patient) Rectal prolapse (below serious, 1 patient) Stomatitis (below serious, 1 patient) Asthenia (below serious, 2 patients) Fatigue (below serious, 5 patients) Feeling abnormal (below serious, 1 patient) Gait disturbance (below serious, 1 patient) Oedema (below serious, 1 patient) Acute sinusitis (below serious, 1 patient) Bronchitis (below serious, 1 patient) Cystitis (below serious, 2 patients) Diverticulitis (below serious, 1 patient) Gastroenteritis (below serious, 2 patients) Gastroenteritis viral (below serious, 1 patient) Herpes zoster (below serious, 2 patients) Pharyngitis streptococcal (below serious, 1 patient) Pneumonia primary atypical (below serious, 1 patient) Tooth infection (below serious, 1 patient) Upper respiratory tract infection (below serious, 5 patients) Urinary tract infection (below serious, 9 patients) Foot fracture (below serious, 1 patient) Muscle injury (below serious, 1 patient) Muscle strain (below serious, 2 patients) Periorbital haematoma (below serious, 1 patient) Procedural pain (below serious, 1 patient) Blood glucose decreased (below serious, 1 patient) Blood pressure increased (below serious, 2 patients) Urine output decreased (below serious, 1 patient) Hyperlipidaemia (below serious, 1 patient) Hypertriglyceridaemia (below serious, 1 patient) Pica (below serious, 1 patient) Polydipsia (below serious, 1 patient) Type 2 diabetes mellitus (below serious, 2 patients) Arthralgia (below serious, 3 patients) Arthritis (below serious, 1 patient) Bursitis (below serious, 1 patient) Flank pain (below serious, 3 patients) Muscle spasms (below serious, 2 patients) Muscular weakness (below serious, 1 patient) Myalgia (below serious, 2 patients) Myositis (below serious, 1 patient) Neck pain (below serious, 1 patient) Pain in extremity (below serious, 2 patients) Basal cell carcinoma (below serious, 1 patient) Amnesia (below serious, 1 patient) Dizziness (below serious, 6 patients) Headache (below serious, 11 patient) Lethargy (below serious, 1 patient) Memory impairment (below serious, 1 patient) Nerve compression (below serious, 1 patient) Paraesthesia (below serious, 1 patient) Syncope (below serious, 1 patient) Tremor (below serious, 1 patient) Depression (below serious, 2 patients) Insomnia (below serious, 5 patients) Dysuria (below serious, 2 patients) Haematuria (below serious, 1 patient) Nephrolithiasis (below serious, 1 patient) Polyuria (below serious, 1 patient) Urinary hesitation (below serious, 2 patients) Urinary incontinence (below serious, 1 patient) Urinary retention (below serious, 3 patients) Urine flow decreased (below serious, 1 patient) Chronic obstructive pulmonary disease (below serious, 1 patient) Dry throat (below serious, 3 patients) Dysphonia (below serious, 2 patients) Dyspnoea (below serious, 1 patient) Epistaxis (below serious, 1 patient) Nasal congestion (below serious, 3 patients) Nasal dryness (below serious, 3 patients) Oropharyngeal pain (below serious, 3 patients) Rhinorrhoea (below serious, 2 patients) Throat irritation (below serious, 1 patient) Dermatitis contact (below serious, 1 patient) Eczema (below serious, 1 patient) Generalised pruritus (below serious, 1 patient) Flushing (below serious, 1 patient) Hypertension (below serious, 3 patients) Vision blurred (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00911937
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01302054	unhealthy n = 308 Health Status: unhealthy Condition: Overactive Bladder Population Size: 308 Sources: https://clinicaltrials.gov/ct2/show/NCT01302054	Other AEs: Angina pectoris, Myocardial infarction... Other AEs: Angina pectoris (serious, 1 patient) Myocardial infarction (serious, 1 patient) Prostate cancer (serious, 1 patient) Chronic obstructive pulmonary disease (serious, 1 patient) Hypertension (serious, 1 patient) Vision blurred (below serious, 3 patients) Constipation (below serious, 12 patients) Dry mouth (below serious, 51 patient) Dyspepsia (below serious, 6 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01302054

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781 substrate 1737	inhibitor 1767 inducer 389	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 P-gp 1461	P-gp 1537	CYP1A2 701 CYP2B6 547 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
P-gp 1650	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/toviaz-epar-scientific-discussion_en.pdf#page=18 Page: 18.0	weak
L-type Ca2+ 7	supressor 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_PharmR_P1.pdf#page=58 Page: 58.0	yes [Inhibition 15 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/toviaz-epar-scientific-discussion_en.pdf#page=15 Page: 15.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 5	yes (co-administration study) Comment: Following blockade of CYP3A4 by coadministration of the potent CYP3A4 inhibitor ketoconazoles, Cmax and AUC of the active metabolite of fesoterodine increased 2.0- and 2.3-fold, respectively, after oral administration of Toviaz to CYP2D6 extensive metabolizers. In CYP2D6 poor metabolizers, Cmax and AUC of the active metabolite of fesoterodine increased 2.1- and 2.5-fold, respectively, during coadministration of ketoconazole. Cmax and AUC were 4.5- and 5.7-fold higher, respectively, in subjects who were CYP2D6 poor metabolizers and taking ketoconazole; Following induction of CYP3A4 by coadministration of rifampicin (inducer), Cmax and AUC of the active metabolite of fesoterodine decreased by approximately 70% and 75%, respectively, after oral administration of Toviaz Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 5	yes (pharmacogenomic study) Comment: CYP2D6 PMs have values for AUC and Cmax that are about 2-fold higher that CYP2D6 EMs Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_PharmR_P1.pdf#page=57 Page: 57.0

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	X5024	http://www.aksci.com/item_detail.php?cat=X5024
Aaron Chemicals	AR00BFSC	http://www.aaronchem.com/286930-02-7
Achemtek	0102-020049	http://www.achemtek.com/286930-02-7
BLD Pharm	BD262927	http://www.bldpharm.com/products/286930-02-7.html
Chem Scene	CS-M2392	http://www.chemscene.com/286930-02-7.html
ChemMol	44025744	http://www.chemmol.com/chemmol/44025744.html
ChemMol	49400560	http://www.chemmol.com/chemmol/49400560.html
ChemMol	49401416	http://www.chemmol.com/chemmol/49401416.html
ChemMol	99063804	http://www.chemmol.com/chemmol/99063804.html
Chemspace	CSSB00020617528	https://chem-space.com/CSSB00020617528
Clearsynth	CS-O-30922	http://www.clearsynth.com/en/CSO30922.html
DC Chemicals	DC23515	http://www.dcchemicals.com/product_show-DC23515.html
Hairui	HR106732	http://www.hairuichem.com/en/product/250214-44-9.html
MedChem Express	HY-70053	https://www.medchemexpress.com/fesoterodine.html
OChem	26230	http://www.ocheminc.com/index.php?act=psearch&pid=930F027
Smolecule	S623538	https://www.smolecule.com/products/s623538
THE BioTek	bt-337449	https://www.thebiotek.com/product/others/bt-337449
THE BioTek	bt-463777	https://www.thebiotek.com/product/others/bt-463777
eNovation Chemicals	D679729	https://www.enovationchem.com/ProductDetails.asp?ProductID=D679729
eNovation Chemicals	Y1048270	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1048270

PubMed

Title	Date	PubMed
Antimuscarinic potency and bladder selectivity of PNU-200577, a major metabolite of tolterodine.	1997 Oct	9353847
Gateways to clinical trials.	2006 Dec	17235418
Gateways to clinical trials.	2006 Jul-Aug	16894408
Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites?	2006 Nov	17021853
Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.	2007 Oct	17651893
Overactive bladder: treatment options in primary care medicine.	2007 Sep	17908830
Fesoterodine: a novel muscarinic receptor antagonist for the treatment of overactive bladder syndrome.	2008 Jul	18570610
Comparison of fesoterodine and tolterodine in patients with overactive bladder.	2008 Nov	18647298
The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis.	2008 Sep	18599186
Fesoterodine for the treatment of urinary incontinence and overactive bladder.	2009	19956551
The design and development of fesoterodine as a prodrug of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine.	2009	19835561
Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.	2009 Apr	19348029
Fesoterodine for the treatment of overactive bladder.	2009 Dec	19920160
Muscarinic receptor antagonists for overactive bladder treatment: does one fit all?	2009 Jan	19057211
Evaluation of drug-drug interactions with fesoterodine.	2009 Jun	19347334
Fesoterodine: a new agent for treating overactive bladder.	2009 Mar	19355800
[Anticholinergic treatment of overactive bladder syndrome. Is it all the same?].	2009 Mar	19145428
The pharmacokinetic profile of fesoterodine: similarities and differences to tolterodine.	2009 Mar 7	19145494
Influence of age, gender, and race on pharmacokinetics, pharmacodynamics, and safety of fesoterodine.	2009 Sep	19761716
Bladder dysfunction in diabetes mellitus.	2010	21833175
Determination of fesoterodine in pharmaceutical formulations by using liquid chromatography-tandem mass spectrometry.	2010	21173462
Medical management of overactive bladder.	2010 Apr	20877608
Durability of treatments for overactive bladder.	2010 Apr	20456203
Long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder symptoms.	2010 Apr	20201992
Efficacy of fesoterodine over 24 hours in subjects with overactive bladder.	2010 Apr	20121659
The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.	2010 Aug	20132203
Efficacy and tolerability of fesoterodine in older and younger subjects with overactive bladder.	2010 Dec	20974482
Fesoterodine fumarate.	2010 Feb	20393636
New Drugs2010, PART 1.	2010 Feb	20083979
The pharmacokinetic profile of fesoterodine 8 mg with daytime or nighttime dosing.	2010 Feb	19915829
Recent advances in management of bladder overactivity.	2010 Feb 11	20948824
Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial.	2010 Jan	20132103
Randomized, double-blind, placebo-controlled trial of flexible-dose fesoterodine in subjects with overactive bladder.	2010 Jan	19931895
The overlap of interstitial cystitis/painful bladder syndrome and overactive bladder.	2010 Jan-Mar	20412643
Urodynamic evaluation of fesoterodine metabolite, doxazosin and their combination in a rat model of partial urethral obstruction.	2010 Jul	19888972
Thorough QT study of the effect of fesoterodine on cardiac repolarization.	2010 May	20420787
Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement?	2010 Sep	20151972
Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects.	2011 Aug	21545485

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of Toviaz (fesoterodine fumarate) is 4 mg once daily. Based upon individual response and tolerability, the dose may be increased to 8 mg once daily. The daily dose of Toviaz should not exceed 4 mg in the following populations: • Patients with severe renal insufficiency (CLCR <30 mL/min). • Patients taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole and clarithromycin.

Route of Administration: Oral

In Vitro Use Guide

In organ-bath studies (rat bladder) fesoterodine and 5-hydroxymethyl tolterodine, induced a concentration-dependent rightward shift of the concentration-response curve for carbachol (1 µM to 1 mM).

Name

Type

Language

DESFESOTERODINE FUMARATE

Common Name

English

(+)-N,N-DIISOPROPYL-3-(2-HYDROXY-5-HYDROXYMETHYLPHENYL)-3-PHENYLPROPYLAMINE FUMARATE

Systematic Name

English

Desfesoterodine fumarate [WHO-DD]

Common Name

English

5-HYDROXYMETHYLTOLTERODINE FUMARATE

Common Name

English

BENZENEMETHANOL, 3-((1R)-3-(BIS(1-METHYLETHYL)AMINO)-1-PHENYLPROPYL)-4-HYDROXY-, (2E)-2-BUTENEDIOATE (1:1) (SALT)

Systematic Name

English

PNU-200577 FUMARATE

Code

English

Code System Code Type Description

PUBCHEM

9825360

Created by admin on Sat Dec 16 09:44:29 GMT 2023 , Edited by admin on Sat Dec 16 09:44:29 GMT 2023

PRIMARY

CAS

380636-50-0

Created by admin on Sat Dec 16 09:44:29 GMT 2023 , Edited by admin on Sat Dec 16 09:44:29 GMT 2023

PRIMARY

SMS_ID

300000035003

Created by admin on Sat Dec 16 09:44:29 GMT 2023 , Edited by admin on Sat Dec 16 09:44:29 GMT 2023

PRIMARY

FDA UNII

607O3D83YQ

Created by admin on Sat Dec 16 09:44:29 GMT 2023 , Edited by admin on Sat Dec 16 09:44:29 GMT 2023

PRIMARY

ACTIVE MOIETY


					YU871O78GR

DESFESOTERODINE

SUBSTANCE RECORD


					607O3D83YQ

DESFESOTERODINE FUMARATE

Details

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Overview

OverviewOther

Drug as perpetrator​

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Sourcing

PubMed

Patents

Sample Use Guides

C_max

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Drug as perpetrator