Oab medical management
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Transcript of Oab medical management
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.
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