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  • At the ICS meeting in Seoul Korea in September 2001, a consensus definition of OAB was derived This definition focuses on the symptoms of OAB rather than on urodynamic parameters and is much more clinically useful for physicians, because most do not do urodynamic studies on patients with OAB In addition, it improves communication between physicians and their patients, since the definition includes terms that are much more intuitive and less likely to confuse or even alarm the patient (many patients have been quite bothered with the old term “unstable” bladder) Thus, the new definition encompasses all of the important clinical aspects of OAB, without using terminology that is only interpretable by a specialist in urology
  • This slide shows the overlap of symptoms for OAB Patients with OAB experience urgency with or without urge incontinence (in fact, only 30% of people with OAB have urge incontinence) Frequency and nocturia are usually associated with urgency; however; these symptoms occurring individually do not constitute a diagnosis of OAB Some women may experience mixed symptoms of stress incontinence and OAB; stress symptoms often resolve with OAB therapy
  • Why should physicians care about OAB? There are several compelling reasons. More patients have OAB than you realize. Overall, 1 out of 6 adults over 40 years of age in Europe has OAB. In France, Germany, Italy, Spain, Sweden, the United Kingdom, Japan, and the United States, the prevalence of OAB ranges from 11% to 22%.   Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. 2001;87:760-766. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-336. Homma Y, Yamaguchi O, Hayashi K, et al. Nation-wide epidemiologic survey on lower urinary tract symptoms in Japan. Presented at: Annual Meeting of the International Continence Society; October 5-9, 2003; Florence, Italy.
  • Psychological —People with OAB often feel guilty about their symptoms, and some become depressed. The embarrassment of leaking or smelling of urine leads to a loss of self-respect and dignity. Social —Overactive bladder sufferers might restrict social activity outside the home for fear of leaking urine or because of the frequent need to use a toilet. Domestic —Some individuals with OAB use disposable pads on the bed during the night or undergarments for incontinence. These items can be costly and are not covered by medical insurance. Occupational —Overactive bladder may lead to decreased productivity in the workplace. Some patients may avoid going to work for fear of leaking urine. Sexual —Women with overactive bladder have reported avoiding dating and sexual intimacy because of overactive bladder symptoms and fear of leaking urine. Physical —Some physical activities like exercising might be limited because of the frequent need to urinate or fear of leaking urine.
  • Women with urge incontinence have an increased diurnal and nocturnal voiding Urge incontinence urgency to rush to bathroom Inability of older women to divide attention.
  • The reasons women seek care for symptoms of pelvic floor disorders vary by age. According to a study within the Kaiser Permanente Health Care program in Southern California, which evaluated the reasons for pelvic floor disorders among 2070 women seeking care, stress urinary incontinence (SUI) was significantly more common among younger women than older women (78% vs 57%, respectively; P  .05). Detrusor instability urge urinary incontinence (UUI) was more common among older vs younger women (67% vs 56%, respectively; P < .05), as was intrinsic sphincter deficiency (5.7% vs 0%, respectively; P < .05). Symptomatic pelvic organ prolapse occurred with equal frequency in older and younger women. Luber KM, Boero S, Choe JY. The demographics of pelvic floor disorders: current observations and future projections. Am J Obstet Gynecol. 2001 ;184:1496-1503.
  • In most cases, a diagnosis of OAB can be made based on patient history, symptoms assessment, physical examination , and urinalysis These assessments are usually sufficient to initiate noninvasive therapy provided you have ruled out the following: Local pathological factors such as infection, bladder stones, bladder tumor/CIS, interstitial cystitis Metabolic factors such as diabetes or polydipsia Medications that may cause OAB symptoms such as diuretics, narcotics, antidepressants, hypnotics, analgesics, sedatives, OTC sleep aids and cold remedies Other factors such as pregnancy or psychologic issues Reasons to refer to a specialist include: Evidence of difficulty in emptying Recurrent urinary tract infection Hematuria Prostate problems Symptomatic prolapse Unsuccessful prior treatment Unsuccessful prior surgery Planned surgery Radical pelvic surgery
  • The challenge rests with primary care physicians to dispel the fears and misconceptions that keep many patients, especially female patients, from seeking treatment for bladder symptoms. Physicians can detect urinary symptoms in reluctant patients during routine medical examination. Additionally, simple questions (such as those listed on the slide) can be used to elicit information needed for diagnosis.
  • This slide and the next list classes of medications that have been shown to influence LUT function.
  • In women, a physical examination can rule out several possible causes of LUTS, including Atrophic vaginitis Estrogen deficiency Pelvic floor dysfunction Prolapse Potentially serious pathologic conditions, such as malignancy Patients with prolapse or other potentially serious conditions should be referred to the appropriate specialist for further evaluation.
  • Urinalysis is an essential component of the patient workup and is used to rule out conditions that may be responsible for LUTS. Laboratory testing on blood is also essential. A prostate-specific antigen test should be administered to adequately informed men older than 50 years of age in accordance with the American Urological Association guidelines. Fantl JA, et al. Urinary incontinence in adults: acute and chronic management. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Policy and Research; 1996. AHCPR publication 96-0686.
  • Specifically, the appropriate laboratory tests should rule out urinary tract infection, sexually transmitted diseases, diabetes, renal disease (including kidney stones), and more serious conditions, such as malignancies. Patients with tumors, kidney stones, or other potentially serious conditions should be referred to the appropriate specialist for further evaluation.
  • Recent data from the NOBLE Program revealed the prevalence of OAB in the United States. A total of 5.1 million people with incontinence have SUI, 6.9 million have UUI, and 5.5 million have MUI (both SUI and UUI). Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol . 2003;20:327-336.
  • OAB is associated with involuntary detrusor contractions. Detrusor instability can cause symptoms of urgency of the sudden loss of urine (UUI). Conversely, SUI can be caused by urethral hypermotility; significant displacement of the urethra and bladder neck during exertion and increased abdominal pressure; or urethral sphincter weakness, in which the bladder sphincter cannot generate enough resistance to retain urine during stress maneuvers. In women, urethral sphincter weakness can occur after trauma, hypoestrogenism, aging, or surgical procedures. Fantl JA, et al. Urinary incontinence in adults: acute and chronic management. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Policy and Research; 1996. AHCPR publication 96-0686.
  • This slide demonstrates the findings that differentiate OAB from SUI and patients with mixed symptoms or MUI. Pertinent points include the following: Urgency and frequency are associated with OAB and MUI, but not with SUI SUI and MUI share symptomatology of leakage during physical activity The amount of urinary leakage typically is much greater in OAB than in SUI Patients with OAB rarely have enough time to reach a toilet compared with patients with SUI, but this varies in patients with MUI Nocturia is more closely associated with OAB than with SUI, and may be present in patients with MUI Abrams P, Wein AJ. The Overactive Bladder. A Widespread and Treatable Condition . Stockholm, Sweden: Erik Sparre Medical AB; 1998.
  • The NOBLE study identified respondents with incontinence based on telephone survey responses. Further investigation (a nested case-controlled study) was conducted on respondents who reported symptoms of OAB. Respondents completed multiple questionnaires (OAB-q, the Medical Outcomes Study [MOS] Short-Form-36 [SF-36], the MOS Sleep Scale, and the Center for Epidemiological Studies — Depression [CES-D] scale) and were categorized according to the primary cause of incontinence: UUI, SUI, or MUI. One hundred seventy-one respondents reported incontinence (UUI: 69; SUI: 62, MUI: 40). Of the respondents, 82.5% were women and the average age was 55.9 years. The findings showed OAB-q subscale scores were significantly worse P < .01) among those with MUI than among those with SUI. In terms of symptom bother, MUI was reported as most bothersome, followed by UUI; respondents with SUI were bothered the least. Coyne KS, Zhou Z, Thompson C, Versi E. The impact on health-related quality of life of stress, urge and mixed urinary incontinence. BJU Int. 2003;92:731-735 .
  • Optional Slide Behavioral modification includes patient education, timed or delayed voiding, pelvic floor exercises, and reinforcement Pelvic floor exercises have been shown to be very useful for women with primarily stress incontinence
  • Bladder Training Bladder training focuses on modifying bladder function by reviewing the bladder diary; the voiding interval should be increased gradually by 15- to 30-minute intervals based on the voiding pattern, and the patient should be taught bladder coping strategies Bladder training is used primarily for urge incontinence, urgency, and frequency Bladder training can be very effective, but it requires ongoing commitment by the patient
  • It has been shown that behavioral therapy alone can improve the symptoms of OAB However, it is often difficult to achieve high compliance with behavioral therapies, and optimal success is dependent on how intense the program is and, in many cases, also requires a high input of caregiver time Studies have shown that the best outcomes are achieved with a combination of pharmacologic and behavioral therapy
  • Currently, antimuscarinic agents are the gold standard for the pharmacologic treatment of OAB Antimuscarinic agents inhibit involuntary bladder contractions and increase bladder capacity, thereby relieving the symptoms of OAB, including urgency, frequency, and urge urinary incontinence However, some antimuscarinic agents, particularly the older ones, are associated with typical anticholinergic side effects that may limit treatment
  • This is a “build” slide showing the distribution of peripheral cholinergic (ie, muscarinic) receptors throughout the body Muscarinic receptors are located in the CNS, iris and ciliary body, lachrymal gland, salivary glands, heart, gallbladder, stomach, colon, and bladder Agents that are selective for the bladder are preferable over agents that may potentially target other regions of the body Blockade of muscarinic receptors outside the bladder may result in undesired side effects such as dry mouth (the most common side effect), constipation, and CNS side effects (such as dizziness, somnolence, and cognitive impairment), and effects on the stomach and eyes
  • In broad terms, the ideal muscarinic agent would provide efficacy by inhibiting involuntary bladder contractions, while having no adverse effect on normal bladder contractions be selective for the bladder over other organs innervated by the parasympathetic system have durable effects, ie, have effects that do not diminish over time Clinically, the ideal agent would provide a balance between efficacy, tolerability, and compliance (persistency); together, these factors comprise “clinical effectiveness”
  • The inclusion criteria consisted of age and OAB symptomatology requirements. Prior therapy was not considered. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421.
  • Patients were randomized 1:1:1 to receive double-blind Detrol ®, 2 mg twice daily; Detrol ® LA, 4 mg once daily; or placebo for 12 weeks. This slide shows the reduction in incontinence episodes after 12 weeks of therapy. Reductions with both Detrol ® treatments were significantly greater than with placebo, with Detrol ® LA being of significantly greater magnitude than Detrol ® . Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421. This slide to be used in conjunction with the following slide
  • Urinary frequency also was reduced 22% to 25% with both Detrol ® formulations, which was significantly greater than with placebo, but there was no significant difference between active treatments. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421.
  • The mean volume voided also increased significantly with both Detrol ® treatments compared with placebo. The difference between active treatments was not significant. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421.
  • Incontinence pad usage was reduced 36% with Detrol ® LA and Detrol ® compared with a 13% reduction with placebo. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421. This slide to be used in conjunction with the following slide
  • Detrol ® LA was better tolerated than Detrol ® . Dry mouth was the most commonly reported side effect for each treatment. Detrol ® LA produced a significant 23% reduction in dry mouth in patients compared with Detrol ® . Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421.
  • This slide shows the incidences of other common anticholinergic adverse events. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421.
  • The percentage of patients who withdrew from the study early because of adverse events was similar among treatment groups and comparable with placebo. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57:414-421. This slide to be used in conjunction with the following slide
  • The registration trial was a 12-week multinational study comparing Detrol ® LA 4 mg once daily, and Detrol ® 2 mg twice daily, with placebo in 1,529 patients. Compared with placebo, Detrol ® LA and Detrol ® were significantly more effective in improving: Incontinence episodes/week Total micturitions/24 hours Mean volume voided/micturition Incontinence pad usage/24 hours For the primary efficacy parameter, Detrol ® LA was also shown to provide significantly greater improvement compared with Detrol ® . In addition, both active treatment groups were associated with positive tolerability and safety profiles. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology . 2001;57:414-421. Key Messages: Detrol ® LA was efficacious in improving all symptoms of OAB Detrol ® LA exhibited a positive tolerability and safety profile Detrol ® LA was shown to produce significantly better improvements in efficacy and tolerability compared with Detrol ®
  • After completion of the phase 3, double-blind, randomized trial of Detrol ® LA, a 12-month open-label extension was performed. This extension was not controlled or randomized. The 1,337 patients who completed the 12-week double-blind phase of the trial were eligible to participate in the open-label extension. Of these patients, 1,077 chose to continue tolterodine treatment; 759 completed the 12-month extension. The primary end point was safety and tolerability of Detrol ® LA, 4 mg qd, and secondary end points were efficacy and persistency. The majority of the participants were women (82.3%), and the mean age was 60.3 years. Kreder K, Mayne C, Jonas U. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • Of the 1,077 patients who chose to remain on Detrol ® LA, 1,075 received treatment and were included in the safety population. Of these patients, 759 completed the 12-month extension. Diary data reported indicate that patients who remained on Detrol ® LA maintained the level of efficacy achieved at 12 weeks through 1 year of treatment. Kreder K, Mayne C, Jonas U. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • The low percentage of adverse events associated with Detrol ® LA treatment at 12 weeks was maintained throughout the12-month open- label study. Kreder K, Mayne C, Jonas U. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • The 12-month open-label extension of the phase 3 trial of Detrol ® LA showed that treatment was well tolerated. Efficacy was maintained for at least 1 year with continued Detrol ® LA treatment. Improvements from baseline in all micturition variables were comparable to those observed at the completion of the 12-week double-blind phase. Seventy-one percent of patients entering the long-term, open-label phase of the pivotal trial were still on Detrol ® LA at 12 months. Kreder K, Mayne C, Jonas U. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • This slide shows the reduction in urge incontinence episodes for naïve and experienced patients at each time point (week 1, week 4, and week 12) There is a substantial reduction from baseline in urge incontinence episodes after only 1 week of treatment in both groups, with further reductions observed at weeks 4 and 12 The reduction in urge incontinence was rapid and significant, and showed a continued benefit over time. These swift results encourage patients to remain on therapy. Median percent reduction from baseline 1 week 4 weeks 12 weeks Na ï ve patients -61.5 -80.0 -85.7 Experienced patients -53.9 -75.0 -75.0
  • This slide shows the reduction in micturition frequency (micturitions/24h) for naïve and experienced patients at each time point (week 1, week 4, and week 12) There is a substantial reduction from baseline in micturition frequency after only 1 week of treatment in both groups, with further reductions observed at weeks 4 and 12 Median percent reduction from baseline 1 week 4 weeks 12 weeks Na ï ve patients -17.1 -25.6 -28.6 Experienced patients -13.9 -20.0 -21.3
  • Percentage of Patients and Physicians Reporting Positive Treatment Benefit at 1 Week Approximately 85% of both naïve and previously treated patients reported benefit from treatment after only 1 week Similarly, physicians independently rated the perception of treatment as beneficial in approximately 85% of patients at 1 week in naïve and experienced patients Yes/little vs. yes/lot vs. none
  • This slide summarizes the results and conclusions from STAT OAB symptoms, as measured by micturition diary parameters, were improved after 1 week of treatment and showed further improvements throughout the 12-week study; these results are consistent with patient perception of treatment benefit Both patients and physicians had a high perception of treatment benefit with tolterodine ER 4 mg once daily as early as 1 week, which was maintained at 12 weeks Most patients will report treatment benefit within 1 week; those who do not will likely report benefit at 4 or 12 weeks
  • Higher incidence of withdrawals reported for oxybutynin IR. This was explained by the higher frequency of withdrawals for adverse events with oxybutynin than with placebo or tolterodine. Other reasons for withdrawal were similar between treatment groups: - lack of efficacy (tolterodine 1.3%, oxybutynin 1.6%, placebo 3.3%) - consent withdrawn - loss to follow-up - protocol violation
  • Compared with placebo, tolterodine ER significantly reduced the median number of mixed incontinence episodes at weeks 1 and 8 (primary endpoint). This reduction was significantly greater than the reduction with placebo as early as 1 week. Further reductions were apparent at 8 weeks. Khullar V, Hill S, Laval K-U, et al. Treatment of urge predominant mixed urinary incontinence with tolterodine: a randomized, placebo-controlled trial. Urology . 2004;64:269-275.
  • Tolterodine therapy also improved other micturition variables compared with placebo; this included significant reductions in the median change from baseline in urinary frequency episodes per day and urgency episodes per day. Volume voided per micturition significantly increased in tolterodine-treated patients compared with those receiving placebo. Khullar V, Hill S, Laval K-U, et al. Treatment of urge predominant mixed urinary incontinence with tolterodine: a randomized, placebo-controlled trial. Urology . 2004;64:269-275.
  • This slide shows the percentage of subjects in both groups reporting treatment benefit at 1 and 8 weeks. At week 8, the percentage of subjects reporting treatment benefit was statistically significantly higher in the tolterodine group compared with the placebo group. Note that the percentage of subjects reporting treatment benefit increased from week 1 to week 8 in the tolterodine group (from 70% to 76%), whereas in the placebo group, the percentage of subjects reporting treatment benefit decreased from week 1 to week 8 (from 64% to 55%). Perception of bladder condition and response to treatment were assessed at baseline after 1 and 8 weeks. Patients rated their bladder condition severity using a validated 6-point rating scale (1 = no problems, 2 = very minor problems, 3 = minor problems, 4 = moderate problems, 5 = severe problems, and 6 = many severe problems). Improvement was defined as a decrease of 1 point or more from baseline. Khullar V, Hill S, Laval K-U, et al. Treatment of urge predominant mixed urinary incontinence with tolterodine: a randomized, placebo-controlled trial. Urology . 2004;64:269-275.
  • Tolterodine was tolerated well and involved fewer withdrawals because of adverse events than placebo. Adverse events were similar between the tolterodine group and the placebo group. The most common adverse event in each treatment group was dry mouth. Khullar V, Hill S, Laval K-U, et al. Treatment of urge predominant mixed urinary incontinence with tolterodine: a randomized, placebo-controlled trial. Urology . 2004;64:269-274.
  • Compared with baseline, statistically significant reductions in incontinence episodes were observed in patients with MUI or UUI treated with tolterodine. There was no significant difference in tolterodine efficacy in patients with MUI compared with UUI. Kreder KJ, Brubaker L, Mainprize T. Tolterodine is equally effective in patients with mixed incontinence and those with urge incontinence alone. BJU Int . 2003;92:418-421
  • Similarly, with all other voiding diary variables, the differences from baseline were significantly improved with tolterodine, but there was no difference in tolterodine efficacy between patients with MUI or UUI. Therefore, tolterodine was equally efficacious in patients with UUI or MUI. Kreder KJ, Brubaker L, Mainprize T. Tolterodine is equally effective in patients with mixed incontinence and those with urge incontinence alone. BMJ Int. 2003;92:418-421.
  • Studies indicate that patients taking Detrusitol ® SR are likely to continue taking it. The longest Detrusitol SR has been studied was in a 1-year open-label continuation study. In this study, 71% of patients were still taking Detrusitol SR at 1 year. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A, on behalf of the Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology . 2001;57:414-421. Siami P, Seidman LS, Lama D. A multicenter, prospective, open-label study of tolterodine extended-release 4 mg for overactive bladder: the Speed of Onset of Therapeutic Assessment Trial (STAT). Clin Ther . 2002;24:616-628. Khullar V, Hill S, Laval K-U, Schi ø tz HA, Jonas U, Versi E. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Urology . 2004; 64:269-274. Kreder K, Mayne C, Jonas U. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • As noted in the registration trial, except for dry mouth, adverse events—including those representing other anticholinergic effects—were similar between Detrusitol ® SR and placebo. There was no difference from placebo in reported events such as dizziness, constipation, or abnormal vision. In a 6-year safety review, Detrusitol SR had no known association with cardiac events. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A, on behalf of the Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology . 2001;57:414-421. Garely AD, Burrows L. Benefit-risk assessment of tolterodine in the treatment of overactive bladder in adults. Drug Saf . 2004;27:1043-1057.

Transcript

  • 1. Pharmacotherapy for Overactive Bladder Rationale for Treatment Choice David A. Ginsberg, M.D. Assistant Professor of Urology USC Keck School of Medicine
  • 2.  
  • 3. Overactive Bladder Terminology
    • OAB = bladder contracting w/o pt’s permission
    • OAB definition per ICS based on symptoms
    • Urgency, with or without urge incontinence, usually with frequency and nocturia
    • In the absence of pathologic or metabolic conditions that might explain these symptoms
    ICS = International Continence Society (www.icsoffice.org)
  • 4. Spectrum of Voiding Dysfunction z
    • Urgency
    • Frequency
    • Nocturia
    SUI Mixed (UUI+SUI) UUI Overactive Bladder Overactive Bladder
  • 5. OAB Affects 11% to 22% of Adults Older Than 40 Years of Age in Europe, Asia, and the United States Milsom I et al. BJU Int . 2001;87:760-766. Stewart WF et al. World J Urol . 2003;20:327-336. Homma Y et al. ICS Abstract 2003. Prevalence of OAB in adults  40 years of age Male Female Prevalence (%) France Germany Italy Spain Sweden UK Japan Country USA 25 20 15 10 5 0
  • 6. Prevalence of OAB by Age and Gender 0 5 10 15 20 25 <25 25-34 35-44 45-54 55-64 65+ Prevalence (%) Age (years) Stewart WF et al. World J Urol. 2003;20:327-336. In a US national telephone survey (N = 5,204). 9 Men: 2.4% (Incontinent) Men: 13.6% (Continent) Women: 9.3% (Incontinent) Women: 7.6% (Continent)
  • 7. Incidence Underreported
    • “ Tip of the iceberg”
    • Increasing incidence in an aging population
  • 8. Incontinence - Underreported
    • Less than half with bladder control problems report it to their health care provider
    • WHY?
    • Embarrassment
    • Low expectation for therapy
    • “ Normal” part of aging
    • Availability of absorbent products/pads
  • 9. Impact of Urinary Incontinence on Quality of Life Quality of Life
    • Psychological
    • Guilt/depression
    • Loss of self-respect and dignity
    • Fear of:
      • being a burden
      • lack of bladder control
      • urine odor
    • Apathy/denial
    • Physical
    • Limitations or cessation of physical activities
    • Sexual
    • Avoidance of sexual contact and intimacy
    • Occupational
    • Absence from work
    • Decreased productivity
    • Social
    • Reduction in social interaction
    • Alteration of travel plans
    • Increased risk of institutionalization of frail older persons
    • Domestic
    • Requirements for specialized underwear, bedding
    • Special precautions with clothing
  • 10. Falls and Fractures
    • In women over 65 years...
    • OAB, falls, and fractures are common
    • 19–42% sustain falls
    • Fractures occur in 4–9% of falls
    • Hip fractures associated with a high rate of morbidity and mortality
    Brown, JAGS 48: 721-725
  • 11. Distribution of Disease Among Women Seeking Care for Pelvic Floor Disorders (N = 602) 67 66 65 72 0 0 5 2 9 6 50 58 77 82 65 56 51 52 33 30 31 34 43 35 0 10 20 30 40 50 60 70 80 90 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 80 - 89 Age Range (Years) Women Affected (%) Urgency/detrusor instability SUI/GSI Pelvic organ prolapse Intrinsic sphincter deficiency Luber KM, et al. Am J Obstet Gynecol . 2001;184:1496-1503. GSI = genuine stress incontinence.
  • 12. Diagnosis of Overactive Bladder
    • Most cases of overactive bladder can be diagnosed based on:
      • patient history, symptom assessment
      • physical examination
      • urinalysis
    • Initiation of noninvasive treatment does not require an extensive further workup
  • 13. Routine Screening
    • Do you frequently limit your fluid intake or map out restrooms when you are away from home?
    • Do you urinate more than 8 times in a 24-hour period?
    • Do you frequently get up 2 or more times at night to go to the bathroom?
    • Do you have uncontrollable urges to urinate, resulting in wetting accidents?
    • Do you use pads to protect your clothes?
    • Are you bothered or concerned about bladder control?
    Questions to Consider
  • 14. History
    • How long? How old when started?
    • How much (volume)? Degree of bother?
    • Characteristics of leakage?
      • Activity related?
      • Day and night, wet pads at night = instability
      • Urgency?
        • Suppressible = probably SUI
        • not suppressible (urge incontinence) = instability
    • Other: fluid intake, UTI’s, pain, hematuria, LE swelling, medications
  • 15. Medications Influencing LUT Function Medication Class Effect Anticholinergic effect, α -receptor antagonist effect Antidepressants, tricyclic Urinary retention, overflow incontinence, fecal impaction Anticholinergics Cough -> SUI ACE inhibitors Urethral relaxation α -Receptor antagonists Urethral constriction and urinary retention (males) α -Receptor agonists Polyuria, frequency, urgency Alcohol
  • 16. Medications Influencing LUT Function (cont)
    • Medication Class
    Effect Anticholinergic effect, sedation Neuroleptics Polyuria, bladder irritation Methylxanthines Polyuria, frequency, urgency Diuretics Sedation, delirium, muscle relaxation Sedative-hypnotics Urinary retention, fecal impaction Opioids Urinary retention, fecal impaction Calcium channel blockers Urinary retention β -Receptor antagonists
  • 17.
    • Abdomen
      • Masses: palpable bladder, etc.
    • Pelvis/perineum
      • External genitalia: atrophic vaginitis
      • vaginal
        • Prolapse (assoc. 50% of SUI patients)
        • GYN malignancy, fistula
    • Rectal:
      • tone, masses, teach Kegels during exam
      • prostate
    • Neurological (reflexes, LE’s, sensory, motor)
    Physical Examination
  • 18. Physical Examination
    • Rule out possible causes of LUTS
      • Atrophic vaginitis
      • Estrogen deficiency
      • Pelvic floor dysfunction
      • Pelvic organ prolapse
      • Potentially serious pathologic conditions
    Conditions Associated With Vaginal Relaxation
    • Cystocele
    • Rectocele
    • Enterocele
    • Uterine prolapse
    Signs of Hypoestrogenation Agglutination of labia minora Prominent caruncle
  • 19. Laboratory Tests
    • Urinalysis
      • Dipstick
      • Culture
      • Microscopic examination
      • Look for hematuria, pyuria, bacteriuria, glucosuria, proteinuria
    • Appropriate blood work
      • Glucose
      • Electrolytes
      • Prostate specific antigen (PSA) in men
    Fantl JA, et al. Agency for Healthcare Policy and Research; 1996. AHCPR publication 96-0686.
  • 20. Laboratory Tests
    • Rule out possible causes of LUTS
      • Urinary tract infection (UTI) or sexually transmitted disease (STD)
      • Diabetes mellitus
      • LUT tumor or kidney stones
      • Potentially serious pathologic conditions
    Refer to appropriate specialist.
  • 21. Stress Incontinence, Overactive Bladder, and Mixed Symptoms
  • 22. Distribution of Urinary Incontinence by Type: United States Total estimated number of people with urinary incontinence: 17.5 million* *Based on 2000 US Census. Adapted from Stewart WF, et al. World J Urol . 2003;20:327-336. Urge 6.9 million Stress 5.1 million Mixed 5.5 million
  • 23. Differentiating OAB With Urge Incontinence From Stress Incontinence OAB and UUI SUI Fantl A, et al. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guidelines No. 2, 1996 Update. Rockville, MD: Agency for Health Care Policy and Research: March 1996. AHCPR publication 96-0682.
  • 24. 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. Maybe Seldom Usually Waking to pass urine at night Variable Yes Often no Ability to reach the toilet in time following an urge to void Variable Small Large (if present) Amount of urinary leakage with each episode of incontinence Yes Yes No Leaking during physical activity (eg, coughing, sneezing, lifting) Yes No Yes Frequency with urgency (> 8 times/24 h) Yes No Yes Urgency (strong, sudden desire to void) Mixed Symptoms SUI OAB Symptoms
  • 25. Mixed Incontinence is the Most Bothersome Coyne KS, et al. BJU Int. 2003;92:731-735. OAB-q Subscale Scores 0 10 20 30 40 50 60 SUI OAB wet* OAB wet + SUI* * P  .05 versus SUI. BOTHER (Quality- of- Life Survey)
  • 26. Treatment for Overactive Bladder
    • Pads
    • Behavioral therapy
    • Medications
    • Neuromodulation
    • Surgery
  • 27. Behavioral Modification Behavioral Modification Education/Log Delayed voiding Timed voiding Diet Pelvic floor exercises
  • 28. Diet Modification
    • Avoid food/beverages irritating to the bladder (coffee, caffeine, etc.)
    • Manage fluid intake
    • Stop evening fluids
    • Avoid constipation
  • 29. Bladder Training
    • Modify bladder function
    • Methods
      • bladder diary
      • gradually increase void interval
      • teach coping strategies
    • Strengthen pelvic floor muscles and improving bladder stability
  • 30. Management of Overactive Bladder
    • Behavioral therapies 1
    • Pharmacologic therapy
    • Combined pharmacologic and behavioral therapy provides improved outcomes 2,3
    1. Mattiasson A. Urology. 2000;55(suppl 5a):12-13. 2. Mattiasson A. Neuro Urodyn . 2001;20:403-404. 3. Burgio et al. JAGS. 2000;48:370-374.
  • 31. Behavioral Modification
    • Burgio, et al
    • 197 women with urge incontinence
    • Modified crossover design
    • Initially on monotherapy of either
      • Behavioral therapy
      • Drug therapy (oxy 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
  • 32. Behavioral Modification
    • Behavioral therapy
      • 57.5% reduction in incontinence
      • 8 pts crossed over
      • 88.5% reduction in incontinence when meds added (p=0.034)
    • Medical therapy
      • 72.7% reduction in incontinence
      • 27 pts 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
  • 33. Pharmacologic Therapy for the Treatment of OAB
    • Antimuscarinic agents are the mainstay for treating OAB
    • OAB symptoms relieved by
      • inhibition of involuntary bladder contractions
      • increased bladder capacity
    • Treatment can be limited by side effects such as dry mouth, GI effects (eg, constipation), and CNS effects
  • 34. Muscarinic Receptor Distribution Abrams P, Wein AJ. The Overactive Bladder— A Widespread and Treatable Condition. 1998. CNS 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
  • 35. 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
  • 36. Anticholinergics A Delicate Balance
    • Efficacy
    • Less frequency
    • Less UUI
    • Increased voided volume
    • Adverse effects
    • Dry mouth
    • Constipation
    • CNS
  • 37. Antimuscarinic Agents
    • Oxybutynin (immediate-release and extended release)
    • Propiverine
    • Tolterodine (immediate-release and extended release)
    • Oxybutynin transdermal delivery system
    • Darifenacin
    • Solifenacin
    • Trospium
  • 38. Tolterodine SR Registration Trial Van Kerrebroeck P et al. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology . 2001;57:414-421.
  • 39. Tolterodine SR in the Treatment of OAB: Study Design and Inclusion Criteria
    • Multicenter (167 sites across North America, Europe, Australia, and New Zealand), randomized, double-blind, active- and placebo-controlled trial in adult patients with symptoms of OAB
    • Adult patients aged 18 or older with symptoms of OAB for >6 months
    • Symptoms of urinary frequency (average of >8 micturitions/24 h) and urge incontinence (>5 incontinence episodes/wk)
    Van Kerrebroeck P et al. Urology . 2001;57:414-421. Detrol ® LA (tolterodine tartrate extended release capsules ) Registration Trial: Van Kerrebroeck et al
  • 40. Tolterodine SR in the Treatment of OAB: Reduction in Incontinence Episodes Van Kerrebroeck P et al. Urology . 2001;57:414-421. – 80 – 60 – 50 – 30 – 20 – 10 0 – 70 – 40 * † * * P < 0.01 vs placebo † P < 0.05 vs tolterodine – 71% – 60% – 33% Median Change From Baseline (%) Placebo Tolterodine Tolterodine SR Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Registration Trial: Van Kerrebroeck et al
  • 41. Tolterodine SR in the Treatment of OAB: Reduction in Total Micturitions/24 Hours – 30 – 25 – 20 – 15 – 10 – 5 0 Mean Change From Baseline (%) * * – 25% – 22% – 15% Placebo * P < 0.001 vs placebo Van Kerrebroeck P et al. Urology . 2001;57:414-421. Tolterodine Tolterodine SR Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Registration Trial: Van Kerrebroeck et al
  • 42. Tolterodine SR in the Treatment of OAB: Increase in Mean Volume Voided/Micturition * P = 0.0001 vs placebo. 0 5 10 15 20 25 30 Placebo Change From Baseline (%) * * 24% 21% 10% Tolterodine SR Tolterodine Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 43. Tolterodine SR in the Treatment of OAB: Reduction in Incontinence Pad Usage – 40 – 35 – 30 – 25 – 20 – 15 – 10 – 5 0 * * – 36% – 36% – 13% Change From Baseline (%) Placebo Tolterodine Tolterodine SR * P < 0.02 vs placebo. Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 44. Tolterodine SR in the Treatment of OAB: Incidence of Dry Mouth
    • The incidence of any dry mouth was:
      • Tolterodine– 30%
      • Tolterodine SR – 23%
    • The rate of dry mouth with tolterodine SR was significantly less than that with tolterodine (P < 0.02)
    Patients (%) 0 10 20 30 40 50 60 Tolterodine SR Tolterodine Placebo 23%* * P < 0.02 vs Detrol ® 30% 8% Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 45. Tolterodine SR in the Treatment of OAB: Incidence of Common Adverse Events 0 2 4 6 8 10 12 14 16 18 20 Constipation Headache Somnolence Patients (%) 5.9% 6.8% 4.3% 6.3% 3.7% 4.6% 2.8% 2.6% 1.8% Placebo Tolterodine SR Tolterodine Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 46. Tolterodine SR in the Treatment of OAB: Withdrawals Due to Adverse Events 0 10 20 30 40 50 60 70 80 90 100 Withdrawal Patients (%) 5% 5% 6% Placebo Tolterodine SR Tolterodine Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 47. Tolterodine SR in the Treatment of OAB: Study Conclusions
    • A 12-week multinational study comparing tolterodine SR 4 mg once daily, and tolterodine 2 mg twice daily with placebo in 1,529 patients
    • Compared with placebo, tolterodine SR and tolterodine were significantly more effective in improving:
      • Incontinence episodes/week
      • Total micturitions/24 hours
      • Mean volume voided/micturition
      • Incontinence pad usage/24 hours
    Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Van Kerrebroeck P et al. Urology . 2001;57:414-421. Registration Trial: Van Kerrebroeck et al
  • 48. 007 Registration Trial: 12-Month Extension Kreder K et al. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. Eur Urol . 2002;41:588-595.
  • 49. Study Design
    • 12-Month open-label, uncontrolled, nonrandomized extension (N = 1,337)
      • 759 patients completed 12-month extension
    • Eligibility
      • Those who completed the 12-week double-blind phase
    • Primary end point
      • Safety and tolerability of tolterodine SR 4 mg qd
    • Secondary end points
      • Efficacy
      • Persistency
    Kreder K et al. Eur Urol . 2002;41:588-595. Detrol ® LA (tolterodine tartrate extended release capsules ) 007 Registration Trial 12-Month Extension: Kreder et al
  • 50. Tolterodine SR: Efficacy Maintained Through 12 Months of Treatment – 100 – 80 – 60 – 40 – 20 0 20 40 12 Weeks 12 Months Median Change From Baseline (%) Urge Incontinence Episodes/Week Micturitions/Week Volume Voided/ Micturition – 18.8 Detrol ® LA (tolterodine tartrate extended release capsules ) Detrol ® (tolterodine tartrate tablets ) Kreder K et al. Eur Urol . 2002;41:588-595. 12-Month Extension: Kreder et al – 80 – 83.1 – 21.3 25 25.4
  • 51. Tolterodine SR: Exhibited Positive Long-term Safety and Tolerability Profile
    • *Incidence of adverse events with onset during the 12-month open-label study period.
    Detrol ® LA (tolterodine tartrate extended release capsules ) Kreder K et al. Eur Urol . 2002;41:588-595. 12-Month Extension: Kreder et al 1.2% Dizziness 1.0% Somnolence 2.4% Headache 3.3% Constipation 12.9% Dry mouth Patients (%)* Adverse Event
  • 52. Conclusions
    • Efficacy of tolterodine SR was maintained for at least 1 year with continued treatment
    • Improvements from baseline in all micturition variables comparable to those observed in the 12-week double-blind phase
    • Long-term treatment with tolterodine SR was well tolerated
    • 71% of patients completed 12 months of therapy
    Detrol ® LA (tolterodine tartrate extended release capsules ) 12-Month Extension: Kreder et al Kreder K et al. Eur Urol . 2002;41:588-595.
  • 53. STAT Speed of Onset Therapeutic Assessment Trial
  • 54. Questions
    • How rapidly does medication work?
    • Does effectiveness increase over time?
    • Is there a difference between patients naïve and non-naïve to prior anticholinergic therapy?
  • 55. Patients
    • 1138 patients
      • 302 men, 836 women
      • 735 naïve, 403 non-naïve
    • Minimum age of 18 years (range 19-91)
    • Diagnosis of OAB
      • Frequency ( > 8 voids/24 hours)
      • Urgency
      • With or without urge incontinence
    • 911 patients (79.4%) completed the study
  • 56. Methods
    • Prospective
    • Multicenter
    • 12-weeks duration
    • Efficacy assessed at 1, 4 & 12 weeks using
      • Micturition diary
      • Patient perception of improvement
      • Physician perception of improvement
  • 57. Medication
    • Treated with tolterodine extended-release (ER)
    • 4 mg daily for 12 weeks
    • If previously on anticholinergics then had 7-day washout
  • 58. Reduction in Urge Incontinence Episodes Over Time – 0 – 10 – 20 – 30 – 40 – 50 – 60 – 70 – 80 – 90 0 1 4 12 Naïve patients Experienced patients Median % Change from Baseline Intent-to-treat analysis Siami P, et al. Clin Ther. 2002;24:616-628. Week
  • 59. Reduction in Micturition Frequency Over Time – 0 – 5 – 10 – 15 – 20 – 25 – 30 0 1 4 12 Naïve patients Experienced patients Intent-to-treat analysis Siami P, et al. Clin Ther. 2002;24:616-628. Median % Change from Baseline Week
  • 60. Patients Reporting Positive Treatment Benefit at 1 & 12 Weeks Intent-to-treat analysis
  • 61. STAT Summary
    • Improvements in efficacy based on patients’ bladder diaries were seen at 1 week, with further improvements noted at 12 weeks
    • Perception of treatment benefit by both patients and physicians was maintained at 12 weeks
    • After only 1 week of treatment, ~85% of patients and physicians reported benefit from treatment
      • half of those patients who reported no treatment benefit at 1 week reported benefit at 12 weeks
  • 62. Efficacy and Tolerability of Tolterodine SR Versus Oxybutynin IR in Japanese and Korean Patients
  • 63. Efficacy
    • Significant reduction between treatment and placebo group
    • No significant difference between Detrol ® LA and oxybutynin IR
    Homma Y et al. BJU Int. 2003;92:741-747. – 1.1 – 2.1 – 2.0 No. voids/24 h – 46.4% – 76.5% – 78.6% Incontinence episode/wk Placebo (n = 122) Tolterodine IR (n = 244) Tolterodine SR (n = 239) Change in Mean Voiding Diary End Points
  • 64. Treatment Withdrawal
    • Total 102 withdrawals (n = 605)
    • Dry mouth accounted for 9.4% of withdrawals in oxybutynin IR and 0.4% in tolterodine SR
    0 5 10 15 20 25 Tolterodine SR Oxybutynin IR Placebo Patients Discontinued, % Withdrawals due to dry mouth Homma Y et al. BJU Int. 2003;92:741-747.
  • 65. Japanese and Korean Study: Conclusions
    • Tolterodine SR has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB
    • Improved tolerability of tolterodine SR resulted in fewer discontinuations of therapy compared with oxybutynin IR
    Homma Y et al. BJU Int. 2003;92:741-747.
  • 66. MERIT M ixed Incontinence E ffectiveness R esearch I nvestigating T olterodine
  • 67. Effect of Tolterodine on Urge-Predominant Mixed Incontinence Episodes – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 0 1 8 Median Change From Baseline (%) Week * * * P < .01 – 50.5% – 77.2% Khullar V, et al. Urology . 2004;64:269-275. 0 Tolterodine ER 4 mg qd Placebo Intent-to-treat analysis.
  • 68. MERIT: Additional Efficacy Endpoints at Week 8 Khullar V, et al. Urology . 2004;64:269-275. Intent-to-treat analysis. P-value Placebo Tolterodine ER 4 mg Endpoint Change from baseline, (%) < .0001 +9.0 +20.5 Volume voided/micturition < .0001 – 19.2 – 37.2 Urgency episodes/24h < .0001 – 13.8 – 20.0 Urinary frequency/24h
  • 69. Patient Assessment of Treatment Benefit After 1 and 8 Weeks Week 1 Week 8 0 10 20 30 40 50 60 70 80 % Improved Tolterodine SR 4 mg qd Placebo * 70% 64% 76% 55% * P < .001 Khullar V, et al. Urology . 2004;64:269-275. Intent-to-treat analysis.
  • 70. MERIT: Tolerability Khullar V, et al. Urology . 2004;64:269-274. 8.1% 19.7% Dry mouth 5.6 % 4.6 % Withdrawal due to adverse events 34 % 39 % Adverse events Placebo Tolterodine SR 4 mg
  • 71. Tolterodine: Comparable Efficacy in Urge Predominant Mixed and Urge Incontinence – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 0 MUI (n = 239) UUI (n = 755) Median Decrease in Incontinence Episodes 67 75 P = NS Kreder K, et al. BJU Int . 2003;92:418-421.
  • 72. Tolterodine in the Treatment of MUI and UUI: Summary of Results *Significant difference versus baseline, but not between MUI and UUI groups Kreder K, et al. BJU Int . 2003;92:418-421. 44 39 Total dryness (%) 76 83 < 2 episodes nocturia (%) – 33 – 50 Nocturia* (%) 27 27 Volume voided* (mL) 24 24 < 8 voids/24 h – 17 – 15 Voiding frequency/24 h* (%) 27 21 No pad usage (%) – 50 – 40 Pad usage* (%) UUI (%) MUI (%)
  • 73. Tolerability: Clinical Trial Continuation Rates With Tolterodine SR Van Kerrebroeck P et al. Urology . 2001;57:414-421. Siami P et al. Clin Ther . 2002;24:616-628. Khullar V et al. Urology . 2004;64:269-274. Kreder K et al. Eur Urol . 2002;41:588-595. 8 12 52 12 Study Duration, wk 92 569 MERIT 80 1138 STAT 71 1077 Kreder K et al 95 507 Registration Trial Patient Continuation Rate, % No. Patients Clinical Study
  • 74. Tolerability: Incidence of Adverse Events* With Tolterodine SR Van Kerrebroeck P et al. Urology. 2001;57:414-421. *Reported by ≥5% of patients in any treatment group or relevant to antimuscarinic therapy during 12 weeks of treatment. 1 0 Dysuria Urinary 2 1 Sinusitis Respiratory 3 2 Somnolence Psychiatric 1 0 Vision abnormal 3 2 Xerophthalmia Vision 3 1 Dyspepsia 4 2 Abdominal pain 6 4 Constipation Gastrointestinal 2 1 Dizziness Central/Peripheral nervous 2 1 Fatigue 6 5 Headache General 23 8 Dry mouth Autonomic nervous Tolterodine SR, % (n = 505) Placebo, % (n = 507) Adverse Event Body System
  • 75. Summary
    • OAB is a highly prevalent condition
    • As our population ages, rates will increase
    • OAB has a large impact on our patient’s quality of life
    • Tolterodine SR is an effective therapy shown to significantly reduce incontinence episodes, reduce urgency and frequency, increase void volume, and reduce pad usage
    • The efficacy of tolterodine SR can be seen as early as 1 week and the effect is maintained with long-term therapy
    • Patients perceive benefit with therapy and improvements in quality of life have been demonstrated
  • 76.