Antimuscarinic drugs for overactive bladder - Mednet

ANTIMUSCARINIC DRUGS

FOR OVERACTIVE BLADDER

Ilan Z Kafka MD 2009

Overactive Bladder

Defining symptoms of overactive bladder syndrome

(OAB) are

Urinary urgency with or without incontinence

Frequency

Nocturia

1 Abrams P Cardozo L Fall M et al The standardization of terminology of

lower urinary tract function report from the Standardization Sub-committee

of the International Continence Societyrdquo Neurourol Urodyn (2002)21 pp

167ndash178

Overactive Bladder

Urge Incontinence

bull Sudden amp involuntary loss of urine

Frequency

bull 8 or more visits to the toilet per 24 hours

Urination at night

bull 2 or more visits to toiletduring sleeping hours

OAB

Urgency

bull Sudden strong desire to urinate

Overactive Bladder

Adapted from Tubaro et al 2004

Overactive Bladder

Local pathology

infection

bladder stones

bladder tumors

interstitial cystitis

outlet obstruction

Metabolic factors

diabetes

polydipsia

Medications

diuretics

antidepressants

antihypertensives

hypnotics amp sedatives

narcotics amp analgesics

Other factors

pregnancy

psychological issues

Ideal Pharmacologic Treatment for OAB

Safety

Metabolic drug-drug interactions

CNS effects

Cardiovascular safety

Efficacy

Alleviate or significantly improve symptoms

Improve QOL

Tolerability

Fewer AEs

Abrams P Wein AJ The Overactive Bladdermdash A

Widespread and Treatable Condition 1998

Bladder (detrusor muscle)

Salivary

glands Dry mouth

Colon Constipation

Heart

Stomach and esophagusDyspepsia

Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS

Distribution of Muscarinic Receptors in Target

Organs of the Parasympathetic Nervous System



Distribution of cholinergic and adrenergic

receptors in the urinary bladder

Antimuscarinic Treatment Options

Tolterodine LA

(Detrusitol) 4 mg Once-daily

Oxybutynin XL

(Lyrinel) 5ndash15 mg Once-daily

Oxybutynin

(Novitropan) 5ndash30 mg BID or TID

Oxybutynin

transdermal patch 39 mgd 1 patch BIW

Trospium (Spasmex) 15 mg TID

Solifenacin (Vesicare)5ndash10 mg Once-daily

Darifenacin

(Enablex) 75ndash15 mg Once-daily

DRUG DOSE FREQUENCY

Are All Antimuscarinics the Same

A meta-analysis found

All antimuscarinics were proven effective for

thetreatment of OAB

Individual antimuscarinic profiles are different

There is some evidence of differences among adverse-

event (AE) profiles

There are differences in tolerability profiles which may

be clinically significant

A systematic review and meta-analysis of randomized controlled trials with

antimuscarinic drugs for overactive bladder

Novara G Galfano A Secco S DElia C Cavalleri S Ficarra V Artibani W

Eur Urol 2008 Oct54(4)740-63

Comparative efficacy antimuscarinic

medications

Study

Drugs

Compared Efficacy Side Effects

Pooled data (Cochrane

2005)

Oxybutinin and

tolterodine

Similar in most outcome

variables

Slightly less dry mouth

and withdrawals with

tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

overall tolerability

similar

Trospium and oxybutinin(Halaska et al 2003)

Oxybutinin and trospium Similar in most outcome

variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER

Solifenacin had slightly

better efficacy than

tolterodine ER

Similar rates of side

effects

Tolterodine and

fesoterodine (Chapple et

al 2008)

Tolterodine and

fesoterodine

Fesoterodine had slightly


tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63

Not All Antimuscarinic Agents Are the Same

Structural differences

Molecular size polarity permeability

Pharmacokinetics and pharmacodynamics

Metabolism and excretionDrug-drug interaction

Efficacy Tolerability Safety

Receptor specificity organ selectivity patient variability

(individual age race gender)

Khullar V et al Urology 200668(2 suppl)38-48

Shaya FT et al Am J Manag Care 200511(4 suppl)S121-S129

Staskin DR Drug Aging 2005221013-1028

Wein AJ Urol 200362(5 suppl 2)20-27

Pak RW et al Curr Urol Rep 20034436-440

Comparison of antimuscarinic Drugs

Hepatic

Impairment

Renal ImpairmentHalf-Life (h)SELECTIVITYDRUG

CautionCaution13ndash19Selective predominantly

M3

Darifenacin

CautionMildmoderate start with 4 mg

increase dose cautiously to 8mg

Severe 4mg

7Non-SelectiveFesoterodine


M1M3

Oxybutynin

CautionMax dose 30mg14-22Non-SelectivePropiverine

CautionMildmoderate no adjustment

Severe max 5mg

45ndash68Selective predominantly

M3

Solifenacin

CautionMildmoderate no data Severe

max 2_1mg IR or 2mg ER

Tolterodine 2ndash3

5-HMT 3-4

Non-SelectiveTolterodine

CautionMildmoderate caution

Severe max 20mg

10ndash20Non-SelectiveTrospium

Antimuscarinic drug Receptor affinity

How do medications used to treat urinary incontinence

affect the cerebral function of the elderly Urologe

2007 middot 46387ndash392

Anticholinergic drugs used for OABS and drugs

that can potentiate their adverse effects

Drugs that can potentiate AErsquos

Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants

Anticholinergic Agents

Anti- emetics

Drugs to treat Parkinsonrsquos

Antispasmodics

MydriaticsCyclopegics

Cognitive Function in Patient Receiving

Antimuscarinic Therapy

Antimuscarinics used in the treatment of overactive bladder differ in their potential to affect cognitive function

In particular treatment with agents that block

M1M3 receptors in the brain are known to cause cognitive impairment

Darifenacin and tolterodine stand out as having been shown to not cause impairment of memory or other cognitive functions in randomized clinical trials

Preserving cognitive function for patients with overactive

bladder evidence for a differential effect with darifenacin

Kay GG Ebinger U Int J Clin Pract 2008 Nov62(11)1792-800

ANTIMUSCARINIC DRUGS FOR OVERACTIVE BLADDER

Two randomized double blind phase III 12-week studies

n = 800

n = 1135

FES 4 or 8mg od vsplacebo (PL)


Active control arm of tolterodine extended

release (TOL ER) 4mg od

Primary endpoints (a) the reduction from baseline (BL) in the mean number of voids per

24-hour period

(b) the reduction in the mean number of episodes of urge incontinence

per 24-hour period both assessed over a 3-day period at study end

(c) treatment response derived from a 4-category pt-assessed

treatment benefit scale


Mean Change in Baseline in No of Voids24 hrs

Kate McKeage Gillian M Keating

FesoterodineDrugs 2009 69 (6) 731-738

p lt 001 p lt 0001 vs PL


Mean Change in Baseline in No episodes in Urge

Incontinence 24h





Patient Responding to Treatment ()Kate McKeage Gillian M Keating

FesoterodineDrugs 2009 69 (6) 731-

738





y = incidence lt1


-Post hoc analysis

-n=1135

-HrQol- Incontinent vs All

-Max Dose Fesoterodine (8mg) vs Max Dose Tolterodine (4mg)

2008Nov102(9)1128-32


Comparison of fesoterodine and tolterodine in patients with overactive bladderChapple

CR Van Kerrebroeck PE Juumlnemann KP Wang JT Brodsky M BJU Int 2008

Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56

n=636 12 week follow-up - double-blind double dummy placebo-controlled RCT

Endpoints - Changes from baseline to week 12 in UUI episodes (primary endpoint)

-Total and nocturnal voids urgency episodes severe urgency episodes and

frequency-urgency sum per 24 h mean voided volume per void (MVV) OAB

questionnaire (OAB-q) Patient Perception of Bladder Condition (PPBC) and

Urgency Perception Scale (UPS)

- Safety and tolerability


P lt 005 vs placebo daggerP lt 005

fesoterodine vs tolterodine ER



fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le

daggerP lt 0001 fesoterodine vs

tolterodine ER (post hoc comparison) DaggerP lt

0001

tolterodine vs placebo (post hoc

comparison)

P lt 0001

fesoterodine vs placebo daggerP = 0014 fesoterodine

vs tolterodine ER (post hoc comparison) The

tolterodine ER vs placebo comparison was not

significant (P = 0167)


Comparison of fesoterodine and tolterodine in patients with overactive bladder

BJU International Volume 102 Issue 9 Date November 2008 Pages 1128-1132

Christopher R Chapple Philip E Van Kerrebroeck Klaus-Peter Juumlnemann Joseph T Wang Marina Brodsky


Urology ARTICLE IN PRESS 2009Nov 13

N= 358 men fesoterodine 4 mg- n =120

fesoterodine 8 mg n = 114

placebo n =124

subanalysis of pooled data


P 05 vs placebo dagger P 05 vs fesoterodine 4 mg


Conclusions

OAB is a highly prevalent condition

As our population ages rates will increase

OAB has a large impact on our patientrsquos quality of

life

Patients perceive benefit with therapy and

improvements in quality of life have been

demonstrated

Pharmacotherapy is better in combination with other

non pharmacological therapies

Conclusions

Multiple OAB agents are available

Many are well proven over years of use and

research

New choices do not necessarily mean better choices

Clinical effectiveness is key

Range of side effects and incidences

M1M3 selectivity may lead to additional

unwanted AEs

THANK YOUhellip

Overactive Bladder

Defining symptoms of overactive bladder syndrome

(OAB) are

Urinary urgency with or without incontinence

Frequency

Nocturia

1 Abrams P Cardozo L Fall M et al The standardization of terminology of

lower urinary tract function report from the Standardization Sub-committee

of the International Continence Societyrdquo Neurourol Urodyn (2002)21 pp

167ndash178

Overactive Bladder

Urge Incontinence


Frequency


Urination at night


OAB

Urgency


Overactive Bladder


Overactive Bladder

Local pathology

infection

bladder stones

bladder tumors


outlet obstruction

Metabolic factors

diabetes

polydipsia

Medications

diuretics

antidepressants

antihypertensives



Other factors

pregnancy



Safety


CNS effects


Efficacy


Improve QOL

Tolerability

Fewer AEs




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip

Overactive Bladder

Urge Incontinence


Frequency


Urination at night


OAB

Urgency


Overactive Bladder


Overactive Bladder

Local pathology

infection

bladder stones

bladder tumors


outlet obstruction

Metabolic factors

diabetes

polydipsia

Medications

diuretics

antidepressants

antihypertensives



Other factors

pregnancy



Safety


CNS effects


Efficacy


Improve QOL

Tolerability

Fewer AEs




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip

Overactive Bladder


Overactive Bladder

Local pathology

infection

bladder stones

bladder tumors


outlet obstruction

Metabolic factors

diabetes

polydipsia

Medications

diuretics

antidepressants

antihypertensives



Other factors

pregnancy



Safety


CNS effects


Efficacy


Improve QOL

Tolerability

Fewer AEs




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip

Overactive Bladder

Local pathology

infection

bladder stones

bladder tumors


outlet obstruction

Metabolic factors

diabetes

polydipsia

Medications

diuretics

antidepressants

antihypertensives



Other factors

pregnancy



Safety


CNS effects


Efficacy


Improve QOL

Tolerability

Fewer AEs




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip


Safety


CNS effects


Efficacy


Improve QOL

Tolerability

Fewer AEs




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




Salivary

glands Dry mouth

Colon Constipation

Heart


Irisciliary body

Lacrimal gland

Blurred vision

Dry eyes

Tachycardia

bull Dizziness

bull Somnolence

bull Impaired

memory and

cognition

CNS








Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip






Tolterodine LA


Oxybutynin XL


Oxybutynin


Oxybutynin




Darifenacin


DRUG DOSE FREQUENCY




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




thetreatment of OAB



event (AE) profiles






Eur Urol 2008 Oct54(4)740-63


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip


medications

Study

Drugs



2005)

Oxybutinin and

tolterodine


variables



tolterodine


2005)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER

OPERA (Diokno et al

2003)

Oxybutinin ER and

tolterodine ER


variables


with tolterodine ER


similar



variables


with trospium

STAR (Chapple et al

2005)

Solifenacin and

tolterodine ER



tolterodine ER


effects

Tolterodine and


al 2008)

Tolterodine and

fesoterodine



tolterodine ER


with tolterodine ER




Eur Urol 2008 Oct54(4)740-63















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip















Hepatic

Impairment



M3

Darifenacin



Severe 4mg



M1M3

Oxybutynin



Severe max 5mg


M3

Solifenacin



Tolterodine 2ndash3

5-HMT 3-4



Severe max 20mg









Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip








Anti-arrythmics

Anti- depressants

Anti-Diarrheal

Antihstamines

Antipsychotics

Muscle Relaxants


Anti- emetics


Antispasmodics













n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip












n = 800

n = 1135






24-hour period












Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip








Incontinence 24h







738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




738





y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




y = incidence lt1


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip


-Post hoc analysis

-n=1135



2008Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




Nov102(9)1128-32




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




Nov102(9)1128-32




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




Nov102(9)1128-32


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip


BJU Int 2010 Vol 105( 1)p58-56













fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip






fesoterodine vs

tolterodine ER

Pati

ent P

erce

ptio

n of

Bla

dder

Cond

itio

n

Urg

en

cy P

erc

ep

tio

n S

ca

le



0001


comparison)

P lt 0001













placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip









placebo n =124





Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip




Conclusions




life



demonstrated



Conclusions



research





unwanted AEs

THANK YOUhellip

Conclusions



research





unwanted AEs

THANK YOUhellip

THANK YOUhellip

Antimuscarinic drugs for overactive bladder - Mednet

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Transcript of Antimuscarinic drugs for overactive bladder - Mednet