Overactive Bladder: A Focus on Women

Overactive Bladder: A Focus on Women ACTIVITY DESCRIPTION With oxybutynin now available OTC, many women may attempt to self manage their overactive bladder (OAB) symptoms. This program will help pharmacists counsel patients on prescription medications for OAB and self management with over the counter agents and behavioral interventions. TARGET AUDIENCE The target audience for this activity is pharmacists, pharmacy technicians, and nurses in hospital, community, and retail pharmacy settings. LEARNING OBJECTIVES After completing this activity, the pharmacist will be able to: Identify urinary symptoms suggestive of overactive bladder List red flags for referral to a urologist or other specialist Describe appropriate treatments to patients including dose/schedule and monitoring parameters After completing this activity, the pharmacy technicians will be able to: List symptoms of overactive bladder List medications used to treat overactive bladder ACCREDITATION Pharmacy PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Nursing PharmCon, Inc. is approved by the California Board of Registered Nursing (Provider Number CEP 13649) and the Florida Board of Nursing (Provider Number 50-3515). Activities approved by the CA BRN and the FL BN are accepted by most State Boards of Nursing. CE hours provided by PharmCon, Inc. meet the ANCC criteria for formally approved continuing education hours. The ACPE is listed by the AANP as an acceptable, accredited continuing education organization for applicants seeking renewal through continuing education credit. For additional information, please visit: http://www.nursecredentialing.org/renewalrequirements.aspx Universal Activity No.: 0798-0000-15-080-H01-P Credits: 1.0 contact hour (0.1 CEU) Release Date: 01/28/2016 freece Expiration Date: 1/28/2018 ACPE Expiration Date: 7/28/2018 ACTIVITY TYPE Knowledge-Based Live Webinar FINANCIAL SUPPORT BY PharmCon

Geneva Briggs, PharmD, BCPS President, Briggs and Associates ABOUT THE AUTHOR Dr. Geneva Clark Briggs, a board-certified Pharmacotherapy Specialist, received her Doctor of Pharmacy and Bachelor of Science in Pharmacy degree from Virginia Commonwealth University, Medical College of Virginia. Additionally, she is the owner of Briggs and Associates. Dr. Briggs was the Chief of Pharmacotherapy at McGuire Veterans Affairs Medical Center and was an Assistant Clinical Professor of Pharmacy and Pharmaceutics at Virginia Commonwealth University, Medical College of Virginia. Prior to becoming Chief of Pharmacotherapy, she was a clinical pharmacy specialist in geriatrics. After she left the Veterans Administration, she worked for MedOutcomes, Inc training pharmacists to provide clinical services in community pharmacies. She has authored numerous articles and textbook chapters. She currently speaks around the country on various topics, and develops continuing education products. FACULTY DISCLOSURE It is the policy of PharmCon, Inc. to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer of any commercial product(s) and/or service(s) discussed in an educational activity. Geneva Briggs reports no actual or potential conflict of interest in relation to this activity. Peer review of the material in this CE activity was conducted to assess and resolve potential conflict of interest. Reviewers unanimously found that the activity is fair balanced and lacks commercial bias. Please Note: PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, faculty may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not intended as a substitute for the participant s own research, or for the participant s own professional judgement or advice for a specific problem or situation. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this activity and other unrelated sources. Neither freece/pharmcon nor any content provider intends to or should be considered to be rendering medical, pharmaceutical, or other professional advice. While freece/pharmcon and its content providers have exercised care in providing information, no guarantee of it s accuracy, timeliness or applicability can be or is made. You assume all risks and responsibilities with respect to any decisions or advice made or given as a result of the use of the content of this activity.

Overactive Bladder: A Focus on Women Overactive Bladder: A Focus on Women Activity ACCREDITATION Learning OBJECTIVES Universal Activity Number Activity 0798-0000-15-080-L01 INSTRUCTION Credits 1.0 contact hour(s) Identify urinary symptoms suggestive of overactive bladder List red flags for referral to a urologist or other specialist Faculty Geneva Clark Briggs, PharmD, BCPS Owner, Briggs and Associates Faculty Disclosure Dr. Briggs has no actual or potential conflicts of interest in relation to this activity. Describe appropriate treatments to patients including dose/schedule and monitoring parameters Legal DISCLAIMER The material presented here does not necessarily reflect the views of PharmCon, Inc. or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. FACULTY: Geneva Clark Briggs, PharmD, BCPS 1/29/2016 2 Overview Disclosures What is overactive bladder (OAB) Red flags for referral to a urologist or other specialist Treatments Behavioral RX OTC Surgical/Interventional No actual or potential conflicts 1/29/2016 3 1/29/2016 4 1

Case Study The Overactive Bladder Complex Beatrice is a 72 year old widow who lives alone. She is well known to you and today confides that she is having some trouble holding her water. She is purchasing incontinence pads Urinates 10-12 times a day, occasionally has to go so bad she can t make it to the bathroom, and gets up 2 times at night to go. Even though this is probably just getting old, I sure wish there was something I could do about it. Nocturia awakening at Night 1 or more times to void Frequency 8 or more Micturitions per day Urgency sudden compelling desire to void that is difficult to defer Urge Incontinence Incontinence associated with urgency 1/29/2016 5 1/29/2016 6 Bladder Function OAB is More than Just Symptoms 2 major functions Store urine Void urine Detrusor muscle Important receptors Muscarinic (acetylcholine) Beta-3 adrenoceptor Vulvovaginitis Skin breakdown and infections Urinary tract infections Depression Falls and fractures 1/29/2016 7 1/29/2016 8 2

OAB VS Stress Incontinence OAB Is Prevalent, Underdiagnosed, and Undertreated Symptoms Urgency (strong, sudden desire to void) Frequency with urgency (> 8 times/24 h) Leaking during physical activity; eg, coughing, sneezing, lifting Amount of urinary leakage with each episode of incontinence Ability to reach the toilet in time following an urge to void Overactive Bladder Yes Yes No Large (if present) Often no Stress Incontinence No No Yes Small Yes OAB Prevalence 33.3 MM Presenting Patients 15.2 MM Diagnosed Patients 6.5 MM 4 out of 5 women with OAB are currently untreated. Waking to pass urine at night Usually Seldom Treated Patients 3 MM Curr Med Res Opin. 2007:23:65-76. Forbes Consulting. Overactive Bladder A&U and Segmentation Report. July 2012. Harris Interactive, Inc. Survey of Adult Women With Overactive Bladder. January 2003. 1/29/2016 9 1/29/2016 10 Risk Factors for OAB Overweight/obesity Menopause BPH Stroke Multiple sclerosis Things that have to be Ruled Out Infection/Inflammation Recurrent urinary tract infection, Chronic prostatitis, Interstitial cystitis Bladder outlet obstruction Urethral stricture, Benign prostatic hyperplasia Bladder pathology Bladder cancer, calculi Behavioral/Iatrogenic Diuresis due to excessive fluid intake, impaired urine concentration, or medications Gormley EA et al. Diagnosis and Treatment of Overactive Bladder (non-neurogenic in adults): AUA/SUFU Guideline. www.auanet.org 1/29/2016 11 1/29/2016 12 3

Red Flags For Evaluation Impact of Overactive Bladder on Quality of Life Frequent UTIs Sensation of incomplete emptying, straining to void Significant pelvic organ prolapse Prior pelvic surgery or radiation therapy Hematuria Neurologic conditions which may affect bladder function Sexual Avoidance of sexual contact and intimacy Occupational Absence from work Decreased productivity Physical Limitations or cessation of physical activities Quality of Life Domestic Require specialized underwear, bedding Special precautions with clothing Psychological Guilt/depression Loss of self-esteem Fear of Being a burden Lack of bladder control Urine odor Social Reduction in social interaction Limit and plan travel around toilet accessibility Res Rep Urol 2014;6:1-6 Urology. 2004;64(suppl 6A):2-6. 1/29/2016 13 1/29/2016 14 Treatment of OAB Education Behavioral Modification Education OAB Treatment Neurostimulation Procedures/ Botox Medications Normal bladder function What is OAB Benefits and risks of treatment Symptom control may require trials of multiple treatment options Patient expectations Getting better versus getting cured Often task oriented for patient instead of number of bathroom visits AUA/SUFU Guideline. www.auanet.org 1/29/2016 15 1/29/2016 16 4

Case Study Beatrice would like to not get up at night to go to bathroom. She fell last week during night She would like to not have accidents. First Line Therapy: Behavioral/Lifestyle Modification Diet avoiding spicy foods, citrus fruits and juices, tomato-based foods, alcohol and drinks with caffeine such as coffee, tea, & cola Don t overly fluid restrict Concentrated urine is irritating Worsen constipation Weight loss 8% loss episodes of incontinence 20% AUA/SUFU Guideline. www.auanet.org N Engl J Med. 2009;360(5):481-90 1/29/2016 17 1/29/2016 18 Behavioral/Lifestyle Modification Modifying bladder function by changing voiding habits Bladder diary Timed voiding Delayed voiding Behavioral training Pelvic floor muscle therapy Biofeedback Behavioral Modification: Medications Combining Both is Most Effective AUA/SUFU Guideline. www.auanet.org J Am Geriatr Soc. 2000;48:370-374 1/29/2016 20 1/29/2016 21 5

Second line therapy: Medication Anti-muscarinics Comparison of Anti-Muscarinic Agents DRUG DOSE DELIVERY Comments Darifenacin (Enablex) 7.5-15 mg QD tablet Can t cut, crush, chew Fesoterodine (Toviaz) 4-8 mg QD tablet Can t cut, crush, chew M 3 receptor antagonism Stabilizes bladder (detrusor) muscle Increases bladder capacity Diminishes frequency of involuntary bladder contractions Delays initial urge to void Oxybutynin ( Oxytrol, Ditropan XL, Ditropan, Gelnique ) 3.9mg -30mg tablet, liquid, patch, gel Patch 2x/wk, gel QD, XL QD, IR BID or TID Solifenacin (Vesicare) 5-10 mg QD tablet Can t cut, crush, chew Tolterodine (Detrol, Detrol LA) Trospium chloride (Sanctura, Sanctura XR ) 1-2 mg bid 2-4 mg QD 20 mg bid 60 mg QD tablet, capsule tablet Can open LA Can t cut, crush, chew can t pm dose XL, extended release; LA, long acting; IR, immediate release 1/29/2016 22 1/29/2016 23 Oxybutynin 3% and 10% Gel (Gelnique ) Applying 3% - 3 complete pumps to dispense one dose 10% - one packet Rub all of the Gelnique gel gently onto one of the following areas until it dries: upper arm/shoulder, thigh, or abdomen. Rotate sites Patients should be advised to: Avoid applying Gelnique to recently shaved skin, open sores, scars, tattoos, or skin with rashes Cover the application site with clothing if close skin-to-skin contact at the application site is anticipated Oxybutynin OTC (Oxytrol ) Transdermal patch Abdomen, hip, or buttock Rotate sites Dose: 1 patch q 4days (3.9 mg/day) AE: skin irritation Maximum effect: 2 weeks Labeled for women over 18 1/29/2016 24 1/29/2016 25 6

Do not use OTC oxybutynin if: Have pain or burning when urinating, blood in your urine, unexplained lower back or side pain, urine that is cloudy, or foulsmelling Are male. Your symptoms may be due to a more serious condition Are under the age of 18. It is not known if it works or is safe in children Only experience accidental urine loss when you cough, sneeze or laugh, you may have stress incontinence. This product will not work for that condition Have urinary retention (are not able to empty your bladder) Have gastric retention (your stomach empties slowly after a meal) Have glaucoma Are allergic to oxybutynin Ask a doctor before use if you have Symptoms of diabetes (excessive thirst, extreme hunger Unexplained weight loss Liver or kidney disease 1/29/2016 26 1/29/2016 27 Ask a doctor or pharmacist before use if you are: Taking a prescription medication for overactive bladder Taking any drugs that may cause sleepiness, dizziness, dry mouth, constipation or blurred vision Taking certain antibiotics (for example, erythromycin, clarithromycin) or prescription antifungals (for example, ketoconazole, itraconazole) Oxybutynin OTC (Oxytrol ) When combined with daily lifestyle modifications (timed urination, pelvic floor exercises and fluid management), patients saw a reduction of the OAB symptom of urinary accidents by 75% vs. 50% with placebo patch. 9% reduction in frequency From 11.5 to 9.5 J Urol. 2002;168:580-586. Urology. 2003;62:237-242. 1/29/2016 28 1/29/2016 29 7

Anti-muscarinics Contraindications Urinary retention Gastric retention Uncontrolled narrow-angle glaucoma Antimuscarinic/Anticholinergic Adverse Effects Constipation Dry mouth Confusion Sedation Blurred vision Heat stroke Gormley EA et al. Diagnosis and Treatment of Overactive Bladder (non-neurogenic in adults): AUA/SUFU Guideline. www.auanet.org 1/29/2016 30 1/29/2016 32 Other Medications with Anticholinergic Effects Beware of Antimuscarinic use in the Frail Elderly Antihistamines -chlorpheniramine,cyproheptadine, diphenhydramine, hydroxyzine Antidepressants - amitriptyline,clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline Gastrointestinal diphenoxylate, atropine, belladonna, clidinium, chlordiazepoxide, dicyclomine, hyoscyamine, propantheline Antiulcer - cimetidine, ranitidine Antiparkinson - amantadine, benztropine Antivertigo meclizine, scopolamine Antiemetics prochlorperazine, promethazine 1/29/2016 33 1/29/2016 34 8

Minimizing Anticholinergic Adverse Effects Minimizing Anticholinergic Adverse Effects Constipation Increase fluid intake Increase dietary fiber Osmotic laxative If no improvement, consider GI evaluation Dry mouth Extended release oxybutynin causes less dry mouth than immediate release Solifenacin < ER tolterodine < fesoterodine & oxybutynin Sip cool water throughout the day Drink milk lubricates oral mucosa Restrict caffeine and alcohol intake Sugar-free gum to stimulate saliva flow Saliva Sure tables, Oral Balance, Biotene toothpaste, Recaldent 1/29/2016 35 Gormley EA et al. Diagnosis and Treatment of Overactive Bladder (non-neurogenic in adults): AUA/SUFU Guideline. www.auanet.org 1/29/2016 36 AUA/SUFU Guideline. www.auanet.org Cochrane Database Syst Rev 2012;1:CD005429 Persistence with Anti-muscarinics can be a Problem Mirabegron (Myrbetriq) Treatment persistence at 3 months (%) Treatment persistence at 12 months (%) Solifena cin Darife nacin Tolterodi ne IR Tolterodi ne ER Oxyb IR Oxyb ER Trospium 58% 52% 46% 47% 40% 44% 42% 35% 17% 24% 28% 22% 26% 26% Selective beta-3 adrenoceptor agonist Activates beta-3 adrenoceptor on the detrusor muscle of bladder to facilitate filling of bladder and storage Does not affect detrusor contractility BJU Int. 2012;110(11):1767 74 1/29/2016 37 1/29/2016 38 9

Mirabegron Starting dose 25mg with or without food Effective within 8 wks, may increase to 50mg Do not cut, crush or chew Renal or Hepatic impairment Max dose 25mg with severe renal impairment or moderate hepatic impairment ESRD and severe hepatic impairment not recommended AE: dry mouth (3%), increase in BP (<3 mm/hg), angioedema Meds for OAB urination by 2-3/day and incontinence by 1-2/day 1/29/2016 39 1/29/2016 40 Combining Medications? Third Line Therapy: Not currently recommended or addressed in AUA guideline. Several trials of solifenacin and mirabegron Better efficacy than either alone No major increase in AE Neuromodulation Percutaneous tibial nerve stimulation Sacral nerve stimulation Intradetrusor Onabotulinum toxin A (Botox) AE: urinary retention and infections Patients must be willing to self cath Arch Gerontol Geriatr 2015 Jun 25. BJU Int 2015 Jan 30. Eur Urol 2015 ;67(3):577-88. 1/29/2016 41 1/29/2016 42 10

Pearls in Treating Patients with OAB Identify most bothersome symptom Make sure patient s expectations are realistic Medications Start low and titrate up as needed Most patients will see some benefit within 2 wks, but will often take at least 4 wks or longer for maximum response Be proactive about preventing/treating side effects Night-time dosing may help decrease adverse effects but should not be used with tropsium chloride Those refractory to behavioral and medical therapy should be evaluated by a urologist Patient Education Resources Urology Care Foundation (American Urological Association) www.urologyhealth.org Link to the AUA/SUFU guidelines and algorithm OAB patient guide www.astellasresources.com Treatment naïve checklist Treatment expectation checklist Patient counseling decks Bladder diary 1/29/2016 43 1/29/2016 44 OAB Conclusions No one therapy is best for everyone 1 st line behavior mod 2 nd line medications ER anti-muscarinics (and topical) have lower rates of AE compared with IR Mirabegron for those with intolerable AE, already on anticholinergics, frail elderly 3 rd line therapies for those who still have bothersome symptoms, especially incontinence 1/29/2016 45 11

Exam Questions: 1. Which of the following is a symptom of over active bladder (OAB)? a. Urge incontinence b. Leaking urine with laughter c. Inability to empty bladder d. Less than 8 episodes of urination in a day 2. Which of the following receptors does acetylcholine bind to which leads to detrusor muscle contraction in the bladder? a. Beta-3 adrenoceptor b. Muscarinic c. 5-HT3 d. Adrenergic 3. Which of the following is a risk factor for OAB? a. Underweight b. Menstruation c. Hypertension d. Multiple sclerosis 4. Which of the following would prompt referral of a patient with OAB to a physician? a. History of hypertension b. Sensation of incomplete emptying or straining to void c. Frequent urination (>10 times per day) d. Nocturia

5. Which of the following is first line therapy for OAB? a. Medication b. Neurostimulation c. Behavioral modification d. Botulinum toxin injections 6. Mirabegeron improves symptoms of OAB by a. Improving bladder capacity b. Stabilizing the detrusor muscle c. Paralyzing the detrusor muscle d. Decreasing transmission of urination signals from bladder to brain 7. Which of the following antimuscarinics causes the highest rate of adverse effects? a. Oxybutynin topical b. Oxybutynin immediate release c. Tolterodine long acting d. Solifenacin 8. Which of the following is an accurate statement on the over the counter oxybutynin patch? a. One patch is applied every 3 days b. The patch can be used as needed c. The most common adverse effect is skin irritation d. Application sites do not need to be rotated

9. Which of the following is the minimum length of a trial of an OAB medication? a. 1 week b. 2 weeks c. 4 weeks d. 12 weeks 10. Which of the following is the adverse effect of most concern with botulinum toxin bladder injections? a. Spread of the toxin beyond the bladder b. Bladder cancer c. Bladder stone formation d. Urinary retention