Presentation is loading. Please wait.

Presentation is loading. Please wait.

Urgent Matters in OAB An FAQ Approach to What You Need to Know Dr. Jeffrey M. Spodek, MD, FRCSC Division Head, Urology Rouge Valley Health System.

Similar presentations


Presentation on theme: "Urgent Matters in OAB An FAQ Approach to What You Need to Know Dr. Jeffrey M. Spodek, MD, FRCSC Division Head, Urology Rouge Valley Health System."— Presentation transcript:

1 Urgent Matters in OAB An FAQ Approach to What You Need to Know Dr. Jeffrey M. Spodek, MD, FRCSC Division Head, Urology Rouge Valley Health System

2 Disclosures  I have served on Advisory Boards and received Consultant Fees from the following companies:  Abbott  Actavis  Astellas  Astra Zeneca  Eli Lily  GSK  Paladin  Pfizer  Sanofi  Triton

3 Disclosure of Commercial Support  Potential for conflict(s) of interest: Dr. Jeffrey M. Spodek has received an honorarium from this event who does not make any products

4 Today’s Program By the end of today’s session, participants will be able to:  Utilize key symptoms and patient screeners to recognize male and female OAB patients needing treatment, and identify patients who should be referred to a specialist  Differentiate between current treatment options, including antimuscarinics, and be confident in initiation of pharmacotherapy  Understand key criteria when individualizing treatment to patient needs

5 LEARNING CHECKPOINT #1 WHAT IS YOUR CURRENT COMFORT LEVEL OF: Identifying patients with OAB needing treatment A Not comfortable at all Somewhat comfortable Comfortable Very comfortable B C D

6 LEARNING CHECKPOINT #2 WHAT IS YOUR CURRENT COMFORT LEVEL OF: Differentiating and initiating antimuscarinics Not comfortable at all Somewhat comfortable Comfortable Very comfortable A B C D

7 LEARNING CHECKPOINT #3 WHAT IS YOUR CURRENT KNOWLEDGE LEVEL OF: Beta-3 receptor agonists and future therapies in OAB management Not knowledgeable at all Somewhat knowledgeable Knowledgeable Very knowledgeable A B C D

8 Overactive Bladder Overview Your guide to tackling OAB in your office Establishing an OAB diagnosis 30 Years of Antimuscarinic Therapy Beta-3 receptor agonists and future therapies in OAB management Wrapping it all up

9 Clinical Definition of OAB IDENTIFYING THE KEY SYMPTOMS OF OAB: Urgency: Sudden, compelling desire to void that is difficult to defer Urgency Incontinence: Involuntary loss of urine preceded by urgency Frequency: The need to frequently urinate (≥8 micturitions/24 hrs) Nocturia: Waking up ≥ 2 times at night to void “Urgency, with or without urgency incontinence, usually associated with frequency and nocturia” Corcos J et al. Can J of Urol. 2006;13(3): ; Abrams P, et al. Neurourol 2002; 21: ; Wein A et al. J Urol Mar;175: :S5-S10; Corcos J, Schick E. Can J of Urology 2004; 11(3):

10 What is Overactive Bladder?  OAB Mechanism Wein AJ, Rovner ES. Int J Fertil. 1999;44:56-66.

11 “Urgency” drives OAB symptoms Adapted from Chapple CR et al BJU Int 2005; 95:

12 Classifying OAB Dry OAB Wet OAB Mixed Incontinence urgency incontinence urgency, frequency without incontinence Involuntary leakage associated with urgency Corcos J, Schick E. Can J of Urology 2004; 11(3): ; Kirby M, et al. Int J Clin Pract 2006; 60: 1263–127; Herschorn S, et al. BJU Int. 2008;101(1): ; Irwin D, et al. EPIC Study. European Urology. 2006;50: % Wet OAB 62% Dry OAB Proportion of OAB Considered a combination of stress and urge incontinence Stress incontinence is involuntary leakage associated with exertion, effort, sneezing or coughing

13 OAB negatively impacts Canadians  Risk of falls/fractures  Economic burden  Emotional  Occupational  Physical 1. Bettez M et al. Can Urol Assoc J 2012;6(5): ; 2. Abrams P et al. Am J Manag Care 2000;6:S580–90; 3. Coyne KS et al. J Sex Med 2007;4:656–66; 4. Stewart WF et al. World J Urol 2003;20:327–36; 5. Brown JS et al. J Am Geriatr Soc 2000;48:721–5; 6. Robertson C et al. British Journal of Urology International. 2007;99: Impacts Quality of Life (QoL) 2-5 Effects more than 1 in 10 Canadians  Sleep  Social  Sexual (13.1% of men and 14.7% of women) of Canadian respondents reported symptoms 1 The effect of moderate urinary symptoms on QoL is similar to that of having diabetes, high blood pressure, or cancer 6

14 Similar Prevalence of OAB in Men and Women Stewart W et al. Prevalence of OAB in the US: results from the NOBLE program. Poster presented at WHO/ICI; July, 2001; Paris, France.

15 OAB remains largely untreated 45–54 years55–64 years≥ 65 years (1,348,901) Number of patients: (1,270,892)(543,420)(1,201,365)(755,218)(2,124,705) (7,244,501) Helfand et al. Eur Urol 2010;57:586–591 Treated Untreated Total untreated (men and women) A large proportion of patients diagnosed with OAB are not taking medication Men with OAB are more frequently untreated than women

16 Overactive Bladder Overview Your guide to tackling OAB in your office Establishing an OAB diagnosis 30 Years of Antimuscarinic Therapy Beta-3 receptor agonists and future therapies in OAB management Wrapping it all up 

17 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

18 OAB: A Secret Condition  Do not always bring up symptoms May be due to lack of knowledge (considered “a natural part of aging”) May be due to embarrassment How do I incorporate diagnosis into my practice? Welch LC et al. Res Nurs Health 2011;34(6): % If they do, approach their primary care physician  Do not routinely ask about urinary symptoms

19 Simple Questions 1.Do you have concerns with your bladder? 2.Do you experience frequency and/or urgency? 3.Do you ever lose urine if you do not make it to the bathroom in time? 4.Do you leak when you laugh/cough/squeeze/lift or strain? You can also have your patients complete the sentence “I hate my bladder because…” How do I incorporate diagnosis into my practice? Start the conversation by asking:

20 OAB Patient Screener How do I incorporate diagnosis into my practice? Patients can screen for OAB in the waiting room:

21 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

22 Assess Patient History What are the most important tests to establish diagnosis? Age (incidence increases with age) Medical history (assess for medications that could cause symptoms) Duration and severity of symptoms Degree of bother/effect on activities of daily life Lifestyle characteristics, including fluid intake Association with other voiding and storage symptoms Prior surgery/ trauma 1. Bettez M et al. Can Urol Assoc J 2012;6(5): Red Flags  Smoker with hematuria  History of complicated recurrent urinary tract infections  Severe symptoms of bladder outlet obstruction  Pain related to the bladder

23 Perform Physical Examination What are the most important tests to establish diagnosis? 1. Bettez M et al. Can Urol Assoc J 2012;6(5): Red Flags  Bladder/pelvic pain Cough test, if appropriate Use to differentiate stress urinary incontinence Abdominal, pelvic, and perineal examination Include digital rectal exam if appropriate Pelvic floor muscle assessment

24 Appropriate Investigations What are the most important tests to establish diagnosis? 1. Bettez M et al. Can Urol Assoc J 2012;6(5): Red Flags  Hematuria (gross or macroscopic)  Elevated PVR (>200 cc) (assume palpable bladder)  Elevated PSA  Complicated positive urine culture Standard recommendation: Urinalysis and culture Optional:  Post-void residual urine (PVR)  PSA, if appropriate  Blood tests  If applicable co-morbidities are present (diabetes, etc.)  Assessment of renal function is not mandatory

25 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

26 Differentiating OAB from SUI and MI SymptomsOAB Stress Urinary Incontinence Mixed Incontinence Urgency (strong, sudden desire to void) YesNoYes Frequency with Urgency ( ≥ 8 times/24hrs) YesNoYes Leaking during physical activity (e.g. coughing, sneezing, lifting) NoYes Amounts of urinary leakage with each episode of incontinence Large (if present) SmallVariable Ability to reach the toilet in time following urge to void Often noYesVariable Nocturia (waking to pass urine at night) UsuallySeldomMaybe Kirby M, et al. Int J Clin Pract 2006; 60: 1263–127. How do I differentiate between similar conditions?

27 REMINDER: OAB IS DEFINED AS “Urgency, with or without urgency incontinence, usually associated with frequency and nocturia” Differential Diagnosis from Related Conditions Presenting Symptom*OABBPH (males)Bladder CancerUTI UrgencyYes OccasionallyYes FrequencyYes OccasionallyYes Nocturnal FrequencyOftenYesRareOften Incomplete emptyingNoYesNo Weak streamNoYesNo Straining/hesitancyNoYesNoOccasionally Elevated PSANoOccasionallyNoCommonly PainNo OccasionallyYes DysuriaNo OccasionallyYes PyuriaNo RareYes HematuriaNoRareYesUsually microscopic * Timing of symptom onset usually very different UTI being acute vs. OAB being chronic Nitti V, Taneja S. Int J Clin Pract. 2005;59: ; Nicolle LE Chapter 127, In: Hazzard’s Geriatric Medicine and Gerontology, 2011; Cornett PA, Dea TO. Chapter 39, In: CURRENT Medical Diagnosis & Treatment 2012, 2011; Prostate Cancer Canada Network: Prostate Cancer Symptoms; Prostate Cancer Cnada Network, Non-Cancerous Conditions: Benign Prostatic Hyperplasia. How do I differentiate between similar conditions?

28 Additional Considerations How do I differentiate between similar conditions? Red Flags  Smoker with hematuria  History of complicated recurrent urinary tract infections  Severe symptoms of bladder outlet obstruction  Bladder/pelvic pain OAB and Interstitial Cystitis OAB and Prostate Cancer Can present with similar symptoms (frequency, urgency, and negative cultures) Key differentiator: Pain Can present with similar symptoms At risk group: older men, abnormal DRE, elevated PSA

29 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

30 A Case of Mistaken Identity Are there specific considerations for males? of men with lower urinary tract symptoms do not have bladder outlet obstruction 1 Sees: a woman who describes LUTS Dr. thinks: Bladder Dr. treats: with Anti- muscarinics Sees: a man who describes LUTS Dr. thinks: Prostate Dr. treats: with Alpha- blockers Many men may present with primary idiopathic OAB 2 1. Chapple C et al. NICE Clinical Guideline. The management of lower urinary tract symptoms in men. May 2010; 2. Bettez M et al. Can Urol Assoc J 2012;6(5):354-63

31 Lower Urinary Tract Symptoms in Men Storage SymptomsVoiding Symptoms Post-Micturition Symptoms  Urgency  Frequency  Incontinence  Nocturia  Poor flow  Intermittency  Straining  Hesitancy  Terminal dribble  Post-void dribble  Incomplete emptying Are there specific considerations for males? Suggestive of OABSuggestive of BOO/BPH However, OAB and BPH frequently co-exist 1. Chapple C et al. NICE Clinical Guideline. The management of lower urinary tract symptoms in men. May 2010; 2. Bettez M et al. Can Urol Assoc J 2012;6(5):354-63

32 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

33 When referral is necessary: “Red Flags”  Consider bladder cancer if: A smoker who with urgency, frequency, pain, and blood in the urine [painless hematuria (gross or microscopic)]  Urine cytology important for patient >40 yrs, smoker, risk factors for bladder cancer, and presence of hematuria  Consider prostate cancer if: Abnormal DRE Elevated PSA 1. Messing EM, et al. Campbell-Walsh Urology, 9th ed. Philadelphia: Saunders; 2007; Nitti V, Taneja S. Int J Clin Pract. 2005; 59: Kelly CE, et al. Rev Urol. 2004;6(Suppl 1): S32–S37.; 4. Ouslander JG. Urology. 2002;60(5 Suppl 1):50-55

34 When referral is necessary: “Red Flags”  Consider post-void residual volume (PVR) if: Non-mobile elderly Presence of neurological disease History suggestive of outflow obstruction  Significant hesitancy and straining to void  Feeling of incomplete emptying (>200 mL)  Previous lower urinary tract surgery Palpable bladder 1. Messing EM, et al. Campbell-Walsh Urology, 9th ed. Philadelphia: Saunders; 2007; Nitti V, Taneja S. Int J Clin Pract. 2005; 59: Kelly CE, et al. Rev Urol. 2004;6(Suppl 1): S32–S37.; 4. Ouslander JG. Urology. 2002;60(5 Suppl 1):50-55  A large PVR can be associated with UTIs, especially in persons at risk (children or patients with spinal cord injury or diabetes)  Very large PVRs (>400 mL) may be associated with an increased risk of renal insufficiency

35 ESTABLISHING AN OAB DIAGNOSIS How do I incorporate diagnosis into my practice? What are the most important tests to establish diagnosis? How do I differentiate between similar conditions? Are there specific considerations for males? Which “red flags” require referral to a specialist? Next Module

36 Overactive Bladder Overview Your guide to tackling OAB in your office Establishing an OAB diagnosis 30 Years of Antimuscarinic Therapy Beta-3 receptor agonists and future therapies in OAB management Wrapping it all up  

37 Clinician’s OAB Toolbox Oxybutynin  Oxybutynin IR  Oxybutynin ER  Oxybutynin CR  Oxybutynin patch  Oxybutynin gel 5-HMT  Tolterodine IR  Tolterodine ER  Fesoterodine Darifenacin Solifenacin Trospium chloride Select agent based on:  Patient and physician preference  Formulary and private coverage  Route and frequency of administration  Receptor and organ selectivity  Potential side effects  Efficacy 1. Bettez M et al. Can Urol Assoc J 2012;6(5):354-63

38 Provincial Public Drug Coverage (Restricted)* BCABSKMNONQCNSNBNFPEI Darifenacin (Enablex) Fesoterodine (Toviaz) Oxybutynin CR (Uromax) Oxybutynin ER (Ditropan XL) Oxybutynin gel (Gelnique) Oxybutynin transdermal patch (Oxytrol) Solifenacin (Vesicare) Tolterodine ER (Detrol LA) Trospium (Trosec) * Limited Use (Special Authorization/Exception drug status), after generic oxybutynin

39 Goals of OAB Treatment Urgency and Frequency Voided volume Urgency incontinence (if applicable)

40 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Are there pharmacological differences that impact tolerability? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module

41 Getting Your Patients On Board What are the options for behavioural therapy?  Counseling patients on how to best incorporate strategies into their lives Adherence to behavioural interventions  Optimal treatment outcomes Patient education is key to optimal treatment outcomes Wyman JF et al. Int J Clin Pract. 2009;63(8):

42 Healthy Bladder Habits What are the options for behavioural therapy? Wyman JF et al. Int J Clin Pract. 2009;63(8):

43 Behavioural Modifications What are the options for behavioural therapy? Wyman JF et al. Int J Clin Pract. 2009;63(8):

44 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module Are there pharmacological differences that impact tolerability?

45 Therapies Block Muscarinic Receptors in the Bladder Gillenwater JY, Grayhack JT, Howards, SS et al. Adult & Pediatric Urology (4th Edition). Philidelphia, PA: Lippincott Williams & Wilkins Mucosa and submucosa (M 2, M 3 ) Bladder neck (α) Pelvic floor (N) Urethra (α) Detrusor muscle (M 2 80%; M 3 20%; β) M = muscarinic N = nicotinic α = α 1 and α 2 –adrenergic Β = β 3 -adrenergic Blocking receptors prevents detrusor contraction Are there pharmacological differences that impact tolerability?

46 Muscarinic Receptors are Distributed Throughout the Body Abrams P., et al. Br J Pharmacol. 2006;148(5): Sellers DJ, et al. Curr Opin Urol. 2007;17: M 1 : Cortex, hippocampus, sympathetic ganglia M 2 : Hindbrain, heart, smooth muscle M 3 : Smooth muscle, brain, glands, heart, M 4 : Basal forebrain, striatum M 5 : Substantia nigra Bladder (detrusor muscle) Colon Constipation Salivary glands Dry mouth Are there pharmacological differences that impact tolerability?

47 Generic Name Darifenacin Feso- terodine Oxybutynin Solifenacin succinate Tolterodin e L-tartrate ER Trospium chloride ERCR Trans- dermal gel Trans- dermal patch Bladder Specificity Moderate None HighModerateNone M 3 Muscarini c Selectivity YesNo YesNo Respective Product Monographs; Hashim H et al, Drugs 2004;64(15): ; Chapple CR et al. BJU Int. 2006:98(supplement 1); Antimuscarinics Agents Antimuscarinic Agents Differ in Their Receptor and Organ Selectivity Are there pharmacological differences that impact tolerability?

48 Commonly Reported Side Effects with Antimuscarinics Respective Product Monographs. Solifenacin succinate is also available in a 10 mg dose. Darifenacin is also available in a 15 mg dose. Fesoterodine is also available in a 8 mg dose. Dry mouthConstipationDry eyesDyspepsiaDizziness Darifenacin (7.5 mg)20.2%14.8%2.1%2.7%0.9% Fesoterodine (4 mg)18.8%4.2%1.4%1.6%n/a Oxybutynin CR (5-20 mg OD)64.0%5.1%2.5%5.1%6.4% Oxybutynin ER (5-30 mg OD) 60.8%13.1%6.1%6.8%6.3% Oxybutynin patch4.1%3.3%n/a Oxybutynin gel6.9%1.3%n/a 1.5% Solifenacin (5 mg OD) 10.9%5.4%0.3%1.4%1.9% Tolterodine ER (4 mg OD) 23.4%5.9%<5% Trospium chloride (20 mg bid)20.1%9.6%1.2% n/a Newer long-acting agents tend to have better tolerability compared to oxybutynin and immediate-release formulations Are there pharmacological differences that impact tolerability?

49 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module Are there pharmacological differences that impact tolerability?

50 Anticholinergics Effectively Reduce OAB Symptoms Buser et al. Eur Urol. 2012;62: Network meta-analysis comparing antimuscarinics in the treatment of OAB Mean reduction in micturitions/24h compared to placebo Solifenacin 10 mg Oxybutynin IR 15 mg Oxybutynin IR 10 mg Fesoterodine 8 mg Trospium chloride 40 mg Solifenacin 5 mg Tolterodine ER 4 mg Oxybutynin gel Fesoterodine 4 mg Oxybutynin ER 15 mg Comparison of efficacy between products?

51 Anticholinergics Effectively Reduce OAB Symptoms Buser et al. Eur Urol. 2012;62: Network meta-analysis comparing antimuscarinics in the treatment of OAB Mean reduction in urgency episodes/24h compared to placebo Solifenacin 10 mg Oxybutynin IR 15 mg Oxybutynin IR 10 mg Fesoterodine 8 mg Trospium chloride 40 mg Solifenacin 5 mg Tolterodine ER 4 mg Oxybutynin gel Fesoterodine 4 mg Oxybutynin ER 15 mg n/a Comparison of efficacy between products?

52 Anticholinergics Effectively Reduce OAB Symptoms Buser et al. Eur Urol. 2012;62: Network meta-analysis comparing antimuscarinics in the treatment of OAB Mean reduction in urgency incontinence episodes/24h compared to placebo Solifenacin 10 mg Oxybutynin IR 15 mg Oxybutynin IR 10 mg Fesoterodine 8 mg Trospium chloride 40 mg Solifenacin 5 mg Tolterodine ER 4 mg Oxybutynin gel Fesoterodine 4 mg Oxybutynin ER 15 mg n/a Comparison of efficacy between products?

53 Head-to-head studies of antimuscarinics Solifenacin 5/10 mg Fesoterodine 8 mg Tolterodine ER 4 mg Fesoterodine 4 mg Tolterodine ER 4 mg Placebo Mean reduction in micturitions/24hrs (primary endpoint) STAR Trial Tolterodine ER vs. Solifenacin Tolterodine ER vs. Fesoterodine * p=0.001 vs. placebo; † p<0.001 vs. placebo; ‡ p=0.004 (non-inferiority) 1. Chapple C et al Eur Urol 2007;52: Corrigendum. Eur Urol 2008;53:1319; 2. Chapple CR et al Eur Urol 2005;48: Head-to-head studies of antimuscarinics BL: * † † ‡ Comparison of efficacy between products? 8.7% 9.4%

54 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module Are there pharmacological differences that impact tolerability?

55 Guidelines advocate the use of antimuscarinics in men  A significant number of patients will have both BPH and OAB In these patients, treat with alpha-blockers or 5-alpha-reductase inhibitors Can antimuscarinics be used in men? of men treated for bladder outlet obstruction have remaining OAB symptoms “Antimuscarinic agents may be used alone as first line therapy when primary idiopathic OAB exists” After 4-6 weeks of alpha- blockers, if storage symptoms persist an antimuscarinic therapy can be started safely if: o PVR is low (<200 mL) o Qmax is > 5 mL/s 1. Bettez M et al. Can Urol Assoc J 2012;6(5):

56 Managing Your AUR Concerns  Assumed increased risk based on what the effect of antimuscarinics may be, but has not been proven scientifically  Actual risk of AUR  Oxybutynin IR mg/day: PlaceboAntimuscarinics ~ 1 in 500 patients 0.2 % ~ 5.5 in 500 patients 1.1 % Incidence with newer agents is ≈ that of placebo Only agent that has shown a statistically significant increase in AUR vs. Placebo Can antimuscarinics be used in men?

57 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module Are there pharmacological differences that impact tolerability?

58 Antimuscarinic Effects in Elderly Patients  Antimuscarinics have the potential to cause CNS impairment: Memory deficits (patients often unaware of this side effect) Sleep disruption Confusion and hallucinations  Extent of CNS effects is determined by: Age related physiology (slower metabolism, drug elimination) Age related changes in Integrity of BBB Age related changes in muscarinic receptors Drug properties that facilitate ability to cross BBB Drug’s propensity to block M1 receptors in the brain Staskin DR. Drugs Aging. 2005;22(12): ; Kay GG. Clinical Geriatrics 2007;15(2;suppl 2):1-14; Ouslander JG. Urology. 2002;60(Suppl 5A): 50–55; Kay GG. OBG Management 2007;19(3;suppl):11-14.

59 Agent Characteristics May Impact Potential for Side Effects  M1 receptors are the primary subtype involved in cognitive function, with M2 playing a lesser role M3 receptors are less concentrated in the brain and CNS  AMs cause side effects by crossing the BBB and binding to muscarinic receptors in the brain Ballert KN and Bales GT. Curr Bladder Dysfunct Rep 2013;8: In theory  More selective for M3 receptors = May cause less side effects (medications such as solifenacin and darifenacin)  Quaternary amine with high polarity and high hydrophilicity, have limited ability to cross the BBB = May cause less CNS side effects (compounds like trospium chloride)

60 2012 SOGC Recommendations for Antimuscarinic-related CNS Effects Elderly and/or cognitively impaired OxybutyninStudies are lacking* FesoterodineSafe to use TrospiumSafe to use SolifenacinSafe to use DarifenacinSafe to use *Not necessarily unsafe but safety studies are lacking  Specific patient factors may make patients susceptible to CNS events:  Increased permeability of the BBB  Comorbid diseases predisposing to adverse CNS effects  Intake of other drugs with anticholinergic effects Geoffrion R et al. J Obstet Gynaecol Can 2012;34(11):

61 30 YEARS OF ANTIMUSCARINIC THERAPY What are the options for behavioural therapy? Comparison of efficacy between products? Can antimuscarinics be used in men? What is the efficacy & tolerability in special populations? Next Module Are there pharmacological differences that impact tolerability?

62 Overactive Bladder Overview Your guide to tackling OAB in your office Establishing an OAB diagnosis 30 Years of Antimuscarinic Therapy Beta-3 receptor agonists and future therapies in OAB management Wrapping it all up   

63 ASK THE AUDIENCE WHAT IS THE MOST IMPORTANT FEATURE OF OAB THERAPY? Efficacy Tolerability Adherence to therapy Newer therapeutic option None of the above A B C D E

64 Levels of Treatment Adherence With Antimuscarinic Treatment Oxybutynin Sexton CC et al. Int J Clin Pract. 2012;65:567–585. A study of patients on antimuscarinics in Quebec shows that over 60% of patients do not refill their prescription and nearly 80% stop using their prescription after 3 months

65 Levels of Treatment Persistence Over 12 Months With Antimuscarinic Treatment Wagg A et al. BJU Int. 2012;110(11): After 12 months, less than 35% of patients were still on antimuscarinic treatment

66 “Real Life” Reasons for Discontinuation of OAB Antimuscarinic Treatment  46% did not work as expected  25% switched to a new medication  23% learned to get by without medication  21% had intolerable side effects Benner JS, Nichol MB, Rovner ES et al. BJU Int. 2010:105(9): Percentages do not add to 100 because multiple reasons were allowed Because of bothersome side effects and a lack of compliance, attempts have been made to develop new compounds

67 Actions of Lower Urinary Treatments Alpha 1 -adrenoceptor antagonists Blockade causes smooth muscle in prostate and bladder neck to relax Improves urine flow & reduces BPH symptoms Onabotulinumtoxin A Inhibits ACh release from presynaptic nerve terminal Prevents stimulation of muscarinic receptors on detrusor muscle Antimuscarinics Inhibits muscarinic receptors Prohibits detrusor muscle contraction Fowler CJ et al. Nature Reviews Urology 2008;(9): ; Nitti VW. Rev Urol. 2006;8(4): ; Solifenacin Product Monograph, 2011; Tamsulosin Product Monograph, 2012; Mirabegron Product Monograph, Onabotulinumtoxin A is now approved for primary idiopathic OAB in Canada

68 Actions of Lower Urinary Treatments Alpha 1 -adrenoceptor antagonists Blockade causes smooth muscle in prostate and bladder neck to relax Improves urine flow & reduces BPH symptoms Beta 3 -adrenoceptor agonists Activation causes detrusor muscle relaxation Increases bladder capacity Does not interfere with the voiding process Onabotulinumtoxin A Inhibits ACh release from presynaptic nerve terminal Prevents stimulation of muscarinic receptors on detrusor muscle Antimuscarinics Inhibits muscarinic receptors Prohibits detrusor muscle contraction Onabotulinumtoxin A is not approved for primary idiopathic OAB in Canada Fowler CJ et al. Nature Reviews Urology 2008;(9): ; Nitti VW. Rev Urol. 2006;8(4): ; Solifenacin Product Monograph, 2011; Tamsulosin Product Monograph, 2012; Mirabegron Product Monograph, 2013.

69 β-3 adrenoceptor (AR) agonists A New OAB Option  The first oral OAB treatment with a distinct MoA since the launch of antimuscarinics agents 30 years ago Mirabegron (Myrbetriq; YM-178; Astellas) is currently approved for use in Canada, the US and Japan Gras J. Drugs of Today. 2012;48(1):25-32.; Sacco E and Bientinesi R. Ther Adv Urol. 2012;4(6):315–324.; Tyagi P, Tyagi V, and Chancellor M. Expert Opin Drug Saf. 2011;10(2): Hicks A, McCafferty GP, Riedel E et al. J Pharmacol Exp Ther. 2007;323(1):

70 Mirabegron Efficacy Compared to Antimuscarinics over 12 weeks (178-CL-046) Mean reduction in OAB symptoms compared to placebo Incontinence episodes/ 24hrs Micturitions/ 24hrs Urgency episodes (Grade 3/4)/24hrs *p=0.003 vs. placebo; **p<0.001 vs. placebo; ***p=0.005 vs. placebo; † p=0.11(NS) vs. placebo; † † p=0.05 vs. placebo Mirabegron Product Monograph, 2013; Khullar V et al. Eur Urol. 2013;63:283–295 Mirabegron demonstrated significant improvements in OAB symptoms, including urgency * ** *** † † ††

71 Improvement in OAB parameters maintained over 12 months (178-CL-049) Chapple CR et al. Eur Urol. 2013;63(2): BL † Mean ± SE. N Mira 50 mg Tolterodine N Mira 50 mg Tolterodine Incontinence † Micturitions † BL Month Mirabegron 50 mg Tolterodine ER 4 mg Adjusted Mean Change From Baseline Month Adjusted Mean Change From Baseline Mirabegron 50 mg Tolterodine ER 4 mg

72 Mirabegron: Safety Compared to Anticholinergic Treatment (12-weeks) Placebo (%) Mirabegron 50 mg (%) Tolterodine ER 4 mg (%) Common TEAEs Any AE43.3%42.8%46.7% Hypertension7.7%5.9%8.1% Nasopharyngitis1.6%2.8% Dry mouth2.6%2.8%10.1% Headache2.8%3.7%3.6% Influenza1.6%2.2%1.4% Urinary tract infection 1.4% 2.0% Constipation1.4%1.6%2.0% Cardiovascular TEAEs QTc prolongation or its sequelae 000.4% Atrial fibrillation of medical importance 0.2%0.4%1.0% Arrhythmia1.0%2.2%3.2% TEAE = treatment-emergent adverse event; Khullar V et al. Eur Urol. 2013;63:283–295

73 How β3-adrenoreceptor Agonists Compare to Existing Therapy Chapple CR et al. Eur Urol. 2013;63(2):296-Khullar V et al. Eur Urol. 2013;63:283–295.; Tyagi P et al. (2011) Mirabegron: a safety review. Expert Opin Drug Saf. 10(2): ; Mirabegron Product Monograph, Astellas Pharma Canada, Inc, AEs Not contraindicated in patients with glaucoma: No difference from placebo for effect on intraocular pressure; Ophthalmological examinations should still be performed as normal Incidence of CNS AE’s did not reach reportable levels in clinical trials and no difference versus placebo  Should have no involvement in cognition and memory  Attractive option for elderly patients? Low incidence of AEs characteristic of antimuscarinic therapy (i.e., dry mouth)  Comparative efficacy Potential for improved patient compliance

74 Overactive Bladder Overview Your guide to tackling OAB in your office Establishing an OAB diagnosis 30 Years of Antimuscarinic Therapy Beta-3 receptor agonists and future therapies in OAB management Wrapping it all up    

75 OAB Can Be Tackled in Your Practice Identify OAB patients needing treatment OAB is common and can have a significant impact on patients’ lives Screen for OAB using simple questions on urgency, frequency, & incontinence Treatment can be initiated without referral Selection of an agent can be based on patient and physician preference, formulary and private coverage, route and frequency of administration, receptor and organ selectivity, potential side effect, and efficacy Successful treatment of OAB depends on both efficacy and tolerability of therapy OAB treatment options continue to improve Despite newer formulations, patient adherence to treatment is low β3-adrenoreceptor (AR) agonists represents an effective new oral treatment option with a low incidence of side effects common to antimuscarinics (i.e., dry mouth)

76 LEARNING CHECKPOINT #1 WHAT IS YOUR CURRENT COMFORT LEVEL OF: Identifying patients with OAB needing treatment Not comfortable at all Somewhat comfortable Comfortable Very comfortable A B C D

77 LEARNING CHECKPOINT #2 WHAT IS YOUR CURRENT COMFORT LEVEL OF: Differentiating and initiating antimuscarinics Not comfortable at all Somewhat comfortable Comfortable Very comfortable A B C D

78 LEARNING CHECKPOINT #3 WHAT IS YOUR CURRENT KNOWLEDGE LEVEL OF: Beta-3 receptor agonists and future therapies in OAB management Not knowledgeable at all Somewhat knowledgeable Knowledgeable Very knowledgeable A B C D

79 COMMENTS/QUESTIONS

80 THANK YOU


Download ppt "Urgent Matters in OAB An FAQ Approach to What You Need to Know Dr. Jeffrey M. Spodek, MD, FRCSC Division Head, Urology Rouge Valley Health System."

Similar presentations


Ads by Google