Faculty Disclosure. Objectives. Spectrum of Voiding Dysfunction. Types of Incontinence/Etiology. Urinary Incontinence Symptom Definitions

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Strategies to Improve Adherence and

Clinical Management of Overactive Bladder:

Prevalence of OAB and Impact on Quality of Life

Dana Saffel, PharmD, CGP

PharmaCare Strategies, Inc.

Santa Rosa Beach, FL

Faculty Disclosure

Dr. Saffel has no actual or potential conflicts of interest in relation

to this presentation.

Objectives

Recognize the prevalence of OAB and the impact of symptoms on

quality of life.

Develop effective treatment plans for older adults with overactive

bladder.

Evaluate the efficacy and safety of current and emerging therapies

for adults with overactive bladder.

Address the current long term care regulations for the evaluation and

management of urinary incontinence.

Minimize medication side effects in treatment plans for older adults

with overactive bladder.

Spectrum of Voiding Dysfunction

z

• Urgency

• Frequency

• Nocturia

SUI

Mixed

(UUI+SUI)

UUI

Overactive Bladder

SUI – stress urinary incontinence UUI – urge urinary incontinence OAB – overactive bladder

Urinary Incontinence Symptom

Definitions

Urinary Stress Incontinence (USI): urinary loss with

“

effort

”

Overflow Incontinence: urinary leakage with retention

Urge Urinary Incontinence: involuntary leakage of urine with or

immediately preceded by urgency

Transient or Functional Incontinence : inability to reach toilet due to

mental or physical condition

Abrams P, et al. Urology. 2003;61:37-49.

Overactive Bladder (OAB) - Urgency, with or without

urge incontinence, usually with frequency and nocturia

Types of Incontinence/Etiology

Urge

Stress

Overflow

Transient

Damage to Damage to bladder nerves bladder nerves Spinal cord Spinal cord Bladder Bladder CancerCancer Multiple sclerosis Multiple sclerosis Parkinson’s Parkinson’s Alzheimer’s Alzheimer’s Stroke Stroke BPH BPH OAB OAB

Weak pelvic floor Weak pelvic floor muscle muscle Multiple Multiple pregnancy pregnancy Pelvic prolapse Pelvic prolapse Weak bladder Weak bladder muscles muscles Diabetes Diabetes Bladder tumors Bladder tumors Urinary stones Urinary stones Delirium Delirium Infection Infection Atrophic urethritis Atrophic urethritis Pharmacologic/ Pharmacologic/ psychological psychological Endocrine disorders Endocrine disorders Restricted mobility Restricted mobility Stool impaction Stool impaction

Steers WD, et al. In: Adult and Pediatric Urology. 4thEd. 2002:1115-1216. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/uiwomen. Accessed 2/1/06.

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Differential Diagnosis: Overactive Bladder,

Stress Incontinence, and Mixed Symptoms

Medical History and Physical Examination Symptom Assessment

Abrams P, Wein AJ. The Overactive Bladder—A Widespread and Treatable Condition.1998.

Symptoms OAB SUI

Mixed Symptom

s Urgency (strong, sudden desire to void) Yes No Yes Frequency with urgency (> 8 times/24 h) Yes No Yes Leaking during physical activity (eg, coughing, sneezing, lifting) No Yes Yes Amount of urinary leakage with each episode of incontinence _{(if present)}Large Small Variable Ability to reach the toilet in time following an urge to void Often no Yes Variable Waking to pass urine at night Usually Seldo_m Maybe

Common Geriatric Diseases that Affect

Continence

Vaginal atrophy

NF Prevalence: >90%

Effect:

inflammation, tenderness, friability of vaginal & urinary tract tissues causing frequency & urgency

Diabetes

NF Prevalence: 32%

Effect:

osmotic diuresis, neuropathy

CHF

NF Prevalence: 22%

Effect:

diuresis

BPH

NF Prevalence: >90%

Effect:

bladder spasms resulting from obstruction & incomplete bladder emptying

UTI

NF Prevalence: 10%

Effect:

bladder irritation with frequency & urgency

Test Your Knowledge

Which of the following descriptions best

describes OAB?

A. Urine leakage during stressful activities (i.e., laughing, sneezing,

jumping, bending)

B. Urine leakage occurring during or immediately after a strong urge

to void

C. Urg

ency and frequency without urine loss

D.

A & B

E.

A & C

Incidence Under-reported

Increasing incidence in an aging population

– but < 50% with bladder control problems

report it to their health care provider

Due to:

Embarrassment

Low expectation for therapy

Belief it’s “normal

”

part of aging

Availability of absorbent products/pads

Fear of having to “move” from ALF

Impact of Urinary Incontinence on

Quality of Life

Quality

of Life

Domestic

• Requirements for specialized underwear, bedding

Occupational

• Absence from work • Decreased

productivity

Sexual

Avoidance of sexual contact and intimacy

Physical

Limitations or cessation of physical activities

Social

• Reduction in social interaction • Alteration of travel plans • Increased risk of institutionalization of frail older persons

Psychological

• Guilt/depression • Loss of self-respect and

dignity • Fear of:

being a burden • lack of bladder control

urine odor • Apathy/denial

Ko y. Am J Manag Care. 2005 Jul;11(4 Suppl):S103-11

Neural Control of the Lower

Urinary Tract

Β

-3

receptors

M3

receptors

M2

receptors

M2

receptors

α

receptors

NE

ACh

NE

N

receptors ACh = acetylcholine.

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Distribution and Function of Muscarinic

Receptors Throughout the Body*

*Muscarinic receptors are expressed in all tissues.

Andersson K-E. Lancet Neurology.2004;3:46-53; Andersson K-E, Yoshida M. Eur Urol. 2003;43:1-5; Chapple CR et al. Urology. 2002;60(suppl 5A):82-89; Choppin A, Eglen RM. Br J Pharmacol. 2001;132:835-842; Collison DJ et al. Invest Opthalmol Vis Sci. 2000;41:2633-2641; Dean B et al. Curr Mol Med. 2003;3:419-426; Kanno H et al. Am J Physiol Cell Physiol.

2003;284:C988–C998; Igawa Y. Urology. 2000;55(suppl 5A):47-49; Seeger T et al. J Neurosci.2004;24:10117-10127; Gautam G et al. Mol Pharmacol. 2004;66:260-267; Anagnostaras S et al. Nature Neurosci. 2002;6:51-58; Wess J. Annu Rev Pharmacol Toxicol. 2004;44:423-450.

Location Function

M

1 Cerebral cortex, hippocampus, salivary glands, eye

Memory and cognitive function, saliva and tear secretion

M

2 Smooth muscle, hippocampus, hindbrain, cardiac muscle, eye, bladder

Heart rate, tear secretion

M

3 Smooth muscle,salivary glands, eye, brain, bladder

Bladder contraction, bowel motility, saliva and tear secretion, visual accommodation

M

4 Basal forebrain striatum, salivary glands Unknown

M

5 Substantia nigra, eye Visual accommodation

Test Your Knowledge

What receptor(S) that are involved with relaxing the bladder wall

to allow for urine storage?

A. M2

B. M3

C. β

3

D. A& B

E. All of the above

Treatment for OAB

Effective Methods of Treating OAB

Pads

Behavioral therapy

Medications

Neuromodulation

Surgery

Combined pharmacologic and behavioral therapy

provides improved outcomes

1,2

1. Mattiasson A. Neuro Urodyn. 2001;20:403-404. 2. Burgio et al. JAGS. 2000;48:370-374.

Behavioral Modification

Behavioral

Modification

Education/Log

Delayed

voiding

Timed

voiding

Diet

Pelvic floor

exercises

Sandip P. Urinary Incontinence Managemeng & Treatment. emedicine.medscape.com/article/452289-treatment. 2014

Diet Modification

Avoid food/beverages irritating to the bladder

(coffee, caffeine, etc.)

Manage fluid intake

Stop evening fluids

Avoid constipation

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Bladder Training

Modify bladder function

Methods

bladder diary

gradually increase void interval

teach coping strategies

Strengthen pelvic floor muscles and

improving bladder stability

Sandip P. Urinary Incontinence Managemeng & Treatment. emedicine.medscape.com/article/452289-treatment. 2014

Behavioral Modification

197 women with urge incontinence

Modified crossover design

Initially on monotherapy of either

Behavioral therapy

Drug therapy (oxybutinin 2.5-15 mg/d)

Combined therapy offered after 8 weeks if not content with

monotherapy alone

Burgio et al. JAGS. 2000;48:370-374

Behavioral Modification

Behavioral therapy

57.5% reduction in incontinence

8 patients crossed over

88.5% reduction in incontinence when meds added (p=0.034)

Medical therapy

72.7% reduction in incontinence

27 patients crossed over

84.3% reduction in incontinence when meds added (p=0.001)

Conclusion:

combining drug & behavioral therapy in a stepped

program can produce added benefit for patients with UUI

Burgio et al. JAGS. 2000;48:370-374

Test Your Knowledge

Behavior modification for the management of urinary

incontinence includes which of the following?

A. Clothes with elastic waist for quick & easy removal

B. Pelvic floor muscle strengthening

C. Delayed voiding

D. A & B

E. B & C

Medication Modification

Medication Class

Effect on LUT

Alcohol

Polyuria, frequency, UUI

α

-Receptor agonists

Urethral constriction and urinary retention (males), OFI

α

-Receptor antagonists

Urethral relaxation, SUI

ACE inhibitors

Cough

→

SUI

Anticholinergics

Urinary retention, fecal impaction, OFI

Antidepressants, tricyclic

Anticholinergic effect, OFI -

α

-receptor antagonist

effect,SUI

LUT – lower urinary tract UUI – urge urinary incontinence OFI – overflow incontinence SUI –stress urinary incontinence

Medications Effecting Lower Urinary Tract Function

Medication Modification (cont)

Medication Class

Effect on LUT

β

-Receptor agonists

Urinary retention, OFI

Calcium channel blockers

Urinary retention, fecal impaction, OFI

Opioids

Urinary retention, fecal impaction, OFI

Sedative-hypnotics

Sedation, delirium, muscle relaxation, UUI

Diuretics

Polyuria, frequency, urgency, UUI

Methylxanthines

Polyuria, bladder irritation, UUI

Neuroleptics

Anticholinergic effect, sedation, OFI

Medications Effecting Lower Urinary Tract Function

LUT – lower urinary tract UUI – urge urinary incontinence OFI – overflow incontinence SUI –stress urinary incontinence

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Pharmacologic Therapy for the

Treatment of OAB

Antimuscarinic agents have been the mainstay for treating OAB

Treatment can be limited by side effects such as dry mouth, GI effects (eg,

constipation), and CNS effects (cognitive impairment)

Newest OAB agent is first-in-class Beta-3 agonist

Avoids anticholinergic side effects

OAB symptoms relieved by

Inhibition of involuntary bladder contractions

Increased bladder capacity

Abrams P, Wein AJ. The Overactive Bladder— A Widespread and Treatable Condition.1998.

Muscarinic Receptor Distribution

Bladder (detrusor muscle) Salivary

glands Dry mouth

Colon Constipation Heart Stomach and esophagus Dyspepsia Iris/ciliary body Lacrimal gland Blurred vision Dry eyes Tachycardia •Dizziness •Somnolence •Impaired memory and cognition

CNS

M2

M1,M2,

M3&M5

M1&M3

M2

M3

M2&M3

M1

Ideal Muscarinic Receptor

Antagonist

Efficacious

inhibits involuntary bladder contractions does not adversely affect volitional detrusor activity

Organ selective

preferentially affects the bladder over other organs results in minimal side effects and improved tolerability

Durable effects

improves compliance and/or persistency

Provides clinical effectiveness

the optimal balance of efficacy, tolerability, and compliance/persistency

Drug Receptor Specificity Initial Dose Max Dose Generic ? Month Cost for Initial Dose Side Effects (max % prevalence) Darifenacin (Enablex) 7.5mg, 15mg ER M3 selective 7.5mg daily 15mg daily No ≈ $150

Dry mouth (35%), constipation (21%), dizziness(2%) abnormal vision (<2%) Fesoterodine (Toviaz) 4mg, 8mg ER Nonspecific for M3 vs M1 4mg daily 8mg daily No

≈ $150 Dry mouth(35%), constipation(6%), fatigue, dizziness, blurred vision(<1%) Oxybutynin (Ditropan) 5mg tab Slightly > M3 than M1 5mg BID -TID 5mg QID Yes ≈ $20 (generic)

Dry mouth(71%), constipation(13%), dizziness(16%), somnolence(13%), blurred vision(9%) Oxybutynin LA (Diitropan XL) 5mg, 10mg, 15mg Slightly > M3 than M1 5mg daily 30mg daily Yes ≈ $75 (generic)

Dry mouth(61%), constipation(13%), somnolence(12%), dizziness(6%), blurred vision(8%) Oxybutynin gel (Gelnique) 3%, 10% Slightly > M3 than M1 84mg daily 84mg daily No

≈ $175 Dry mouth(12%), application site _{reactions (5%), blurred vision,} constipation, pruritus (<2%) Oxybutynin Patch (Oxytrol – Rx) (Oxytrol for Women - OTC) 3.9mg Slightly > M3 than M1 3.9mg twice weekly 3.9mg twice weekly No ≈ $225 (Rx) ≈ $15 (OTC)

Application pruritus (14%), dry mouth (4%), constipation(3%), abnormal vision(2.5%), fatigue, somnolence, headache (<2%)

Medications for Overactive Bladder. Pharmacist’s Letter. PL Document #281002. October 2012.

Antimuscarinic Agents for OAB

Drug _SpecificityReceptor Initial _Dose _DoseMax Generic ? Month Cost for Initial Dose Side Effects (max % prevalence) Solifenacin (Vesicare) 5mg, 10mg tab Slightly > M3 than M1 5mg daily 10mg daily No ≈ $190 Drug mouth(28%), constipation(13%), blurred vision(5%), fatigue(2%) Tolterodine (Detrol) 1mg, 2mg tab Nonspecific for M3 vs M1 1mg BID 2mg BID Yes ≈ $120

(generic) Dry mouth(35%), constipation(7%),_{fatigue(4%), dizziness(5%)} Tolterodine LA (Detrol LA) 2mg, 4mg, ER cap Nonspecific for M3 vs M1 2mg daily 4mg daily No

≈ $174 Dry mouth(23%), constipation(6%), somnolence (3%), fatigue(2%), dizziness(2%), abnormal vision(1%) Trospium (Sanctura) 20mg tab Nonspecific for M3 vs M1 20mg BID 20mg BID Yes

≈ $100 Dry mouth(20%), constipation(10%), blurred vision(<1%) Trospium LA (Sanctura XR) 60mg ER cap Nonspecific for M3 vs M1 60mg daily 60mg daily No ≈ $190

Dry mouth(10%), constipation(9%), blurred vision, somnolence (<1%)

Antimuscarinic Agents for OAB (con’t)

Drug Receptor Specificity Initial Dose Max Dose Generic ? Month Cost for Initial Dose Side Effects (max % prevalence) Mirabegron (Myrbetriq)

25mg, 50mg ER tab Beta-3 agonist 25mg daily 50mg daily No ≈ $210 Hypertension(7.5%), headache(3.2%), constipation, arthralgia, diarrhea, tachycardia, abdominal pain, fatigue (all <2%)