Update On oab joon Chul Kim

Update On OAB

• Joon Chul Kim

• The Catholic University of Korea

Overactive Bladder Syndrome : ICS Definition

• Urgency, with or without urge incontinence, usually with frequency and nocturia

• Absence of pathologic or metabolic conditions that might explain these symptoms

• Urgency - Sudden, compelling desire to pass urine that is difficult to defer

OAB Initiating Treatment

• If there is no significant abnormality of physical exam, urine analysis and PVR, treatment for OAB can be initiated without further workup

• In some cases where abnormalities are found, treatment can be initiated, but abnormality must be worked up (e.g. hematuria)

• UDS in select patients

Antimuscarinics 2008 in Korea

• Oxybutynin IR BID-TID

• Oxybutynin ER QD

• Tolterodine IR/ER BID / QD

• Trospium BID / QD*

• Solifenacin QD

What’s The Difference??

• Efficacy

• No great differences
• Dose dependent

• Tolerability

• Safety

• Clinical Effectiveness – different for different patients depending on expectations

Differences Among Anticholinergics

• Metabolism

• Hepatic
• Renal

• Pharmacokinetics

• Delivery system
• Bioavailability

• Receptor selectivity

• Chemical structure

• Permeability

• Dose titration

• 50-60% of patients will choose higher dose

Why is Efficacy So Hard to Measure in the OAB Population

• Different patients have different:

• Primary bother symptoms
• Expectations from treatment

• Different studies have different populations

Side Effects: Dry Mouth Incidence

• Drug Placebo

• Oxybutynin ER 10mg 28.1-29.7% n.a.

• Tolterodine ER 4mg 23% 8%

• Oxybutynin TDS 9.6% 8.3%

• Solifenicin 5 mg 14% 4.9%

• Solifenicin 10 mg 21.3% 4.9%

• Darifenicin 7.5 mg 18.8% 13.2%

• Darifenicin 15 mg 31.3% 13.2%

Side Effects: Constipation Incidence

• Drug Placebo

• Oxybutynin ER 10mg 6.4-7.0% n.a.

• Tolterodine ER 4mg 6% 4%

• Oxybutynin TDS <2% <2%

• Solifenicin 5mg 7.2% 1.9%

• Solifenicin 10 mg 7.8% 1.9%

• Darifenicin 7.5mg 14.8% 6.7%

• Darifenicin 15mg 21.3% 6.7%

Urgency: Defining Symptom of OAB

• How is it measured?

• Yes/no
• Degree
• VAS, IUSS, UPS
• Warning time
• OAB voids

• Recent studies have shown positive effects on antimuscarinics on urgency

• Darifenicin and solifenicin using yes/no scales
• Tolterodine and trospium using fixed scales
• Darifenicin using a VAS

Reduction in Urgency Episodes/24 hrs

Improvement in IUSS Score: Baseline to End of Study

Improvement in Urgency Perception Score: Baseline to End of Study

Tolterodine LA Nighttime Dosing Reduced 24-Hour Frequency

Individual Agents Advantages and Drawbacks

Oxybutynin - ER

• Advantages

• Widest range of dose titration
• Only compound approved for “high dose” administration

• Drawbacks

• Effects on cognitive function

Tolterodine

• Advantages

• Long safety record
• Number 1 prescribed drug
• New CNS data favorable
• Data on male OAB

• Drawbacks:

• Lack of titration
• Mild increase in QT interval at super therapeutic doses

Trospium

• Advantages

• No hepatic metabolism
• Less drug-drug interactions
• Less crossing of blood-brain barrier
• ? Clinical correlation at this time
• Higher urine concentration
• ? Clinical meaning

Solifenicin

• Advantages

• Dose titration
• Relatively low dry mouth incidence

• Drawbacks

• Mild increase in QT interval at super therapeutic doses

Antimuscarinics Summary

• Efficacy among antimuscarinic agents is similar

• There are several different advantages (some theoretical) which may influence drug choice in a particular patient

• Expect in cases of high dose antimuscarinics, decisions are more likely to revolve around tolerability and safety (or perceived safety)

Male LUTS Can Be Associated With the Bladder, the Prostate, or Both

Timing of combination treatment

• Primary vs. Add-on

• : Many patients with BPH and OAB have benefit

• from alpha blocker only

• : Initially treated with an alpha blocker

• : Anticholinergics is added in patients who report

• partial response to the alpha blocker but still

• have persistent OAB symptoms

In Men With OAB, Treatment With Tolterodine Was Not Associated With Increased Incidence of AUR

TIMES Study : Urinary Retention Summary

Several recent clinical trials have refuted

• Several recent clinical trials have refuted

• But, given the exclusion criteria should be considered

• Exclusion criteria for PVR in clinical trials

• - greater than 30-40% of maximum capacity

• - or 50-200ml

Post-void residual volume should be measured to exclude baseline urinary retention

• Post-void residual volume should be measured to exclude baseline urinary retention

• The safety in patients with baseline urinary retention is not known

Summary: OAB in Men

• Available data suggests that antimuscarinics are safe in men with OAB + BOO, but PVR should be considered

• Optimal way to use + alpha blockers needs to be sorted out

• It should be evaluated which patient benefit from adding of antimuscarinics initially in real life practice