FESOTERODINE FUMARATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H37NO3.C4H4O4
Molecular Weight	527.649
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=C(OC(=O)C(C)C)C=CC(CO)=C2)C(C)C

InChI

InChIKey=MWHXMIASLKXGBU-RNCYCKTQSA-N

InChI=1S/C26H37NO3.C4H4O4/c1-18(2)26(29)30-25-13-12-21(17-28)16-24(25)23(22-10-8-7-9-11-22)14-15-27(19(3)4)20(5)6;5-3(6)1-2-4(7)8/h7-13,16,18-20,23,28H,14-15,17H2,1-6H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t23-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C26H37NO3
Molecular Weight	411.5769
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19835561
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18279452

Fesoterodine (trade name Toviaz) is a prodrug of 5-hydroxymethyl tolterodine, which is also the active metabolite of tolterodine. Fesoterodine and its active metabolites are nonsubtype selective, competitive antagonists of human muscarinic receptors, but 5-hydroxymethyl tolterodine has greater potency than the parent compound. A prodrug approach was necessary for systemic bioavailability of 5-hydroxymethyl tolterodine after oral administration. Fesoterodine was originated by Schwarz Pharma (later a subsidiary of UCB) and is being developed by Pfizer for the treatment of overactive bladder and urinary urge incontinence. The agent is launched in several countries for the treatment of overactive bladder, including the US, Japan, Canada, Europe and Asia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2737	8.0 null [pKi]
Muscarinic acetylcholine receptor M2 120 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2737	7.7 null [pKi]
Muscarinic acetylcholine receptor M3 158 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2737	7.4 null [pKi]
Muscarinic acetylcholine receptor M4 85 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2737	7.3 null [pKi]
Muscarinic acetylcholine receptor M5 61 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2737	7.5 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 34 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	Palliative		Approved 8307	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 1.22532476E12
Overactive bladder 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022030lbl.pdf	Primary		Approved 8307	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 1.22541126E12

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 1532 inducer 753 substrate 1670	inhibitor 1695 inducer 372	inhibitor 1789 substrate 1168	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP2E1 846 P-gp 1401	P-gp 1491	CYP1A2 671 CYP2B6 521 CYP2C19 283

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
CYP3A4 1857	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 2
P-gp 1588	inhibitor 3185 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+ 4	supressor 149 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 1491	substrate 3264 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/toviaz-epar-scientific-discussion_en.pdf#page=15 Page: 15.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 2	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 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 2	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 1603	inhibitor 1584 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
Gateways to clinical trials.	2006 Dec	17235418
Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo.	2008 Apr	18279452
Pharmacokinetic profile of fesoterodine.	2008 Nov	19000553
The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis.	2008 Sep	18599186
The safety and efficacy of tolterodine extended release in the treatment of overactive bladder in the elderly.	2009	19503781
Fesoterodine.	2009	19405552
Fesoterodine for the treatment of overactive bladder.	2009 Aug	19638887
Efficacy and tolerability of fesoterodine in women with overactive bladder.	2009 Jul	19495545
Influence of food on the pharmacokinetic profile of fesoterodine.	2009 Jun	19473600
Fesoterodine: a new agent for treating overactive bladder.	2009 Mar	19355800
Fesoterodine (toviaz) for overactive bladder.	2009 May 4	19417719
Tolterodine extended-release for overactive bladder.	2009 Sep	19663610
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
Spinal effects of the fesoterodine metabolite 5-hydroxymethyl tolterodine and/or doxazosin in rats with or without partial urethral obstruction.	2010 Aug	20639056
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
New Drugs2010, PART 1.	2010 Feb	20083979
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
Efficacy and tolerability of fesoterodine in men with overactive bladder: a pooled analysis of 2 phase III studies.	2010 May	19914702
Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement?	2010 Sep	20151972
Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence.	2010 Sep 14	20840754

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).

Substance Class	Chemical Created by `admin` on `Fri Dec 16 17:25:29 UTC 2022` Edited by `admin` on `Fri Dec 16 17:25:29 UTC 2022`
Record UNII	EOS72165S7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FESOTERODINE FUMARATE

Official Name

English

FESOTERODINE FUMARATE [MI]

Common Name

English

2-((1R)-3-(BIS(1-METHYLETHYL)AMINO)-1-PHENYLPROPYL)-4-(HYDROXYMETHYL)PHENYL 2-METHYLPROPANOATE HYDROGEN(2E)-BUTENEDIOATE (SALT)

Common Name

English

SPM 907

Code

English

FESOTERODINE FUMARATE [JAN]

Common Name

English

FESOTERODINE FUMARATE [VANDF]

Common Name

English

FESOTERODINE FUMARATE [MART.]

Common Name

English

FESOTERODINE FUMARATE [ORANGE BOOK]

Common Name

English

SPM-907

Code

English

SPM-8272

Code

English

FESOTERODINE FUMARATE [EMA EPAR]

Common Name

English

SPM 8272

Code

English

FESOTERODINE FUMARATE [USAN]

Common Name

English

Fesoterodine Fumarate [WHO-DD]

Common Name

English

TOVIAZ

Brand Name

English

PROPANOIC ACID,2-METHYL ,2-((1R)-3-(BIS(1-METHYLETHYL)AMINO)-1-PHENYLPROPYL)-4-(HYDROXYMETHYL)PHENYL ESTER,(2E)-2-BUTENEDIOATE (1:1)(SALT)

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

TOVIAZ (AUTHORIZED: URINARY BLADDER, OVERACTIVE)