OAB, OverActive Bladder

MEDICAL MANAGEMENT

Dr Clarence Lei Chang Moh, FRCS Urol,

Consultant Urologist

• Adjunct Professor, Universiti Malaysia Sarawak

• Honorary Consultant to SGH & HKL

• c/o Kidney & Urology Centre, Normah Hospital, KUCHING.

• clarencelei@gmail.com

BORNEO REGIONAL UROLOGY WORKSHOP, Kota Kinabalu, 9-10 July 2011

DRUGS: Anticholinergics

Ideal medication for OAB

• an ideal agent must balance– Efficacy (rapid onset of action, relief of OAB symptoms)

– Tolerability (side effects e.g. dry mouth)

• compliance

• Combined calcium channel & phosphodiesterase inhibition + local anesthetic:

– flavoxate (URISPAS)

• Combined antimuscarinic & calcium channel inhibitor:

– Oxybutynin (DITROPAN 5mg 8 hrly)

– Propiverine (MICTONORM 15mg 1-4 OD)

• Pure antimuscarinic:

– Trospium (SPASMOLYT 20mg 1 12 hrly)

– tolterodine (DETRUSITOL 2 mg 12 hrly or SR 4 mg OD)

– solifenacin (Vesicare® 5-10 mg daily)

Medications for OAB

Chemical formulas for antimuscarinics

OH

O

ON

Oxybutynin

O

N Tolterodine

O

N

O

NDarifenacin

N

NO

O

OH

O

OH

O

Vesicare®

(solifenacin succinate)

Vesicare• Solifenacin is well tolerated

– Phase I studies showed no decrease in salivary flow with solifenacin 5 mg

– Adverse event profile limited to common class effectsPharmacokinetics

– Similar in age, gender, and ethnic groups– No dose adjustment required with concomitant drug

use but dose should be restricted to 5 mg when used simultaneously with potent CYP3A4 inhibitors

Patient-friendly dosing regimen:

– Once daily; with or without food

Smulders RA et al., ICS 2002. CL-002 Poster Smith N et al. ICS 2002 CL010 Poster

Vesicare®: “rapid” onset of action

Cardozo L, et al. BJU Int 2008;102:1120–1127

Solifenacin

• Solifenacin showed significant improvement in urgency as early as day 3 of treatment

• There was also an early onset of significant treatment effect for micturition frequency, incontinence episodes, and urgency incontinence episodes

Efficacy results

Placebo 5 mg Solifenacin 10 mg Solifenacin

Cardozo L et al. Urology 2004 172; 1919-1924

-3

-2

-1

0

Mea

n r

edu

ctio

n in

mea

n n

um

ber

of

mic

turi

tion

s/24

h

P=0.0002

P=0.0001

-13%

-20%

-22%

N=281 N=261 N=290

Micturition frequency /24hr

PP=0.014=0.014-1.5

-1

-0.5

0

Mea

n r

edu

ctio

n in

mea

n n

um

ber

of

urg

e in

con

tin

ence

ep

isod

es/2

4 h

PP=0.042=0.042

-43%

-63%-57%

N=126 N=141 N=138

Urge incontinence episodes/24hr

-3

-2

-1

0

Mea

n r

edu

ctio

n in

mea

n n

um

ber

of

urg

ency

ep

isod

es/2

4 h

PP=0.005=0.005PP=0.0001=0.0001

-33%

-51%-52%

N=278 N=284 N=298

Urgency episodes/24hr

0

10

20

30

40

Mea

n in

crea

se in

vol

um

e vo

ided

(m

L)

per

mic

turi

tion

P=0.0001

P=0.0001

7%

21%

25%

N=281 N=286 N=290

Volume voided/micturition

Reduction in key efficacy parametersby exposure time

Frequency

Nocturia

-100%

-80%

-60%

-40%

-20%

0%4 Weeks 8 Weeks 12 Weeks 16 Weeks 28 Weeks 40 Weeks 52 Weeks

Urgency

Urge incontinence

Mea

n p

erce

nta

ge

red

uct

ion

Haab F et al. Eur Urol 2005.

Tolerability at 52 weeks compared with placebo-controlled studies

Solifenacin 10mg (n=575)

Solifenacin 5mg (n=578)

Placebo (n=568)

Per

cen

tage

ad

vers

e ev

ents

12 week data

0

5

10

15

20

25

Dry Mouth Constipation

4%

11%

19%

2%

5%

9%

Solifenacin 5mg

Solifenacin 10mg

Solifenacin All

Per

cen

tage

ad

vers

e ev

ents

52 week data

0

5

10

15

20

25

Dry Mouth Constipation

10%

17%

21%

5%

8%10%

Haab F et al. Eur Urol 2005.

Completion and withdrawal rates during a 12-month, open-label study

of tolterodine*

Kreder K, et al. Eur Urol. 2002;41:588-95.

*4 mg od

70.6

10.0 9.9

Per

cen

t

Completion rate

Withdrawal due to lack of efficacy

Withdrawal due to adverse events

0

20

40

60

80

100

STAR study• Vesicare® (solifenacin) 5mg showed greater

improvements than tolterodine ER 4mg across all symptoms of OAB at 4 weeks

1.71

1.22

1.98

1.3

0.51

1.21

1.47

0.91

1.67

0.9

0.44

0.8

0

0.5

1

1.5

2

2.5

Micturitionfrequency

Urgeincontinence

Urgency Overallincontinence

Nocturia Pad use

Solifenacin 5mg N=578

tolterodine ER 4mg N=599

Mean improvement in OAB symptoms at 4 weeks

Mea

n s

ymp

tom

imp

rove

men

t

P<0.05P<0.05

Adverse Events for Solifenacin 5 mg

Adverse EventSolifenacin 5 mg

(%)

Dry mouth 17.5

Constipation 11.6

Blurred vision 2.3

Discontinued due to all AEs 3.6

Data on file. Astellas Pharma US, Inc.

Why Do We Treat Men Differently than Women When It Comes to OAB?

FemaleFemale MaleMale

ProstateProstate

• In men and women, symptoms of OAB are the same; anatomy is In men and women, symptoms of OAB are the same; anatomy is differentdifferent

• In men, LUTS are considered related predominantly to the prostate In men, LUTS are considered related predominantly to the prostate due to BPHdue to BPH

BPH, LUTS lower urinary tract symptoms

Voiding symptoms, caused by an enlarged prostate Weak urinary stream Prolonged voiding Abdominal straining Hesitancy Intermittency Incomplete bladder emptying Terminal and post-void

dribbling

Storage symptoms, which can result from enlarged prostate or overactive bladder (OAB)FrequencyNocturiaUrgencyIncontinence

LUTS are not specific to BPH – not all men with LUTS have BPH and not all men with BPH have LUTS

Associated symptoms of BPH include: DysuriaHaematuriaHaematospermia

For medical healthcare professionals’ information only

Men: BPH + OAB

• OAB symptoms often persist after pharmacologic or surgical treatment of BOO

• Studies provide evidence of the safety and usefulness of anticholinergics in men with OAB who also have BOO

• There was no increase in urinary retention in 4 recent studies when anticholinergics used in men with BOO

• Combination therapy provide improved symptom relief for men with LUTS

Lee et al. BJU Int. 2004;94:817-820 .Athanasopoulos et al. J Urol. 2003;169:2253-2256.

Kaplan S et al. Abstract. AUA 2004.Abrams et al. Neurourol Urodyn. 2001;20:5547-548.IR = immediate release; ER = extended release.

Please see full prescribing information.

How long do I take medications?

• “Forever” NO !• "Long term, till better, trial off medications,

followup”

Can I be cured?Can be controlled, adjust lifestyle, trial of medications

Summary

Vesicare® showed rapid onset of action

Vesicare® is effective across all the main symptoms of OAB, especially urgency (including measurements by warning time)

This effect improves over the long-term with the majority of patients staying on treatment

Vesicare® offers good balance between efficacy and tolerability

Vesicare® 5/10mg have been shown to be superior to tolterodine ER 4mg across the main parameters of OAB

SARAWAK – Dr Lei

Enjoy? TQ !

Hilton Batang Air Borneo Heights

Tree hse

Q & A

ALTERNATIVE THERAPY(non medicinal)

• Sacromodulation

• TENS

• Acupuncture

• Acupressure

• Reflexology

ALTERNATIVE THERAPY• Saw Palmetto/Pumpkin

• Zn/Selenium

• Traditional Chinese

* Saw Palmetto for BPH. NEJM 2006; 354: 557-66

* Saw Palmetto not active. J Urol 2002; 168: 150-4

LUTS + Pain

NEGATIVE urine, scan, US etc.

• Urethral Syndrome

• PBS

• CPPS

• Chronic testicular pain

LUTS + Pain + PCNEGATIVE culture

• I.C. - interstitial cystitis

• TB

• ketamine

LUTS & Sex

eg Cialis 5 mg OD - Sex rehab, better LUTS

UNWILLING, unable to payCost, cut tab, cheaper

PRN treatment vs“lifelong”

Plavix, statins

Should drs use expensive drugs like Vesicare? etc

THANK YOU !

Normah Medical Specialist Centre(wholly owned by Sarawak State Government)

USA