Presentation Goals Pharmacology for Urinary Incontinence in Women Medications Review anti muscarinic medications Focus on newer meds Introduce beta adrenergic medications Current Concepts in Drug Therapy University of Washington Leah Gordon, MD MPH 4/24/15 Question 1 A 60 year old woman with urge incontinence has pursued behavioral modification and pelvic floor training but continues to be bothered by frequent episodes of incontinence and is interested in pharmacologic treatment. She has no other medical problems. She has heard these medications can be expensive and is worried about the potential cost. a. Oxybutynin (Ditropan XL) 30mg po daily b. Fesoterodine (Toviaz) 4mg po daily d. Mirabegron (Myrbetriq) 25mg po daily Question 1 1
Answer 1 Which medication would be appropriate to start for her? a. Oxybutynin (Ditropan XL) 30mg po daily b. Fesoterodine (Toviaz) 4mg po daily d. Mirabegron (Myrbetriq) 25mg po daily S P E C I F I C I T Y OXYBUTYNIN = Ditropan FESOTERODINE = Toviaz TOLTERODINE = Detrol SOLIFENACIN = Vesicare DARIFENACIN = Enablex TROSPIUM = Sanctura M 3 Primary Outcomes in Most Studies: Complete Continence = NO incontinent episodes Clinically Important Improvement = reduction in frequency of incontinent episodes by at least 50% Quality of Life All Anti Muscarinics: Many large, well done RCTs BEST effects reduced incontinence or have clinically important improvement in 20% of women. NO big differences in efficacy across meds 2
Answer 1 An Approach Start Cheap Side Effects? Specific Cases Which medication would be appropriate to start for her? a. Oxybutynin (Ditropan XL) 30mg po daily b. Fesoterodine (Toviaz) 4mg po daily d. Mirabegron (Myrbetriq) 25mg po daily Question 2 Question 2 A 55 year old woman with urge incontinence as well as atrial fibrillation, depression, and diabetes on Metformin, Fluoxetine, and Metoprolol is interested in starting a medication for her incontinence. a. Darifenacin (Enablex) 7.5mg po daily b. Trospium (Sanctura) 20 mg po daily 3
Answer 2 a. Darifenacin (Enablex) 7.5mg po daily b. Trospium (Sanctura) 20 mg po daily Start Cheap Side Effects? Specific Cases Answer 2 Start Cheap Side Effects? Interactions a. Darifenacin (Enablex) 7.5mg po daily b. Trospium (Sanctura) 20 mg po daily Trospium 4
Question 3 A 65 year old woman with mixed stress/urge incontinence and no other co morbidities was previously on Trospium without improvement. She is now interested in trying a different medication. switch to for her? a. Oxybutynin (Ditropan) 5mg po daily b. Trospium (Sanctura) 60mg po daily c. Darifenacin (Enablex) 7.5mg po daily Question 3 Answer 3 a. Oxybutynin (Ditropan) 5mg po daily b. Trospium (Sanctura) 60mg po daily c. Darifenacin (Enablex) 7.5mg po daily Start Cheap Side Effects? Prior treatment? Solifenacin 5
Answer 3 a. Oxybutynin (Ditropan) 5mg po daily b. Trospium (Sanctura) 60mg po daily c. Darifenacin (Enablex) 7.5mg po daily Question 4 A 60 year old woman with early Alzheimer s disease on Donepezil is very bothered by urge incontinence and wants to start a medication. a. Mirabegron (Myrbetriq) 25mg po daily b. Solabegron mg po daily c. Oxybutynin (Ditropan) 5mg po daily d. Trospium (Sanctura) 60mg po daily Question 4 Answer 4 a. Mirabegron (Myrbetriq) 25mg po daily b. Solabegron mg po daily c. Oxybutynin (Ditropan) 5mg po daily d. Trospium (Sanctura) 60mg po daily 6
Beta adrenergics Caution in: Cognitive Impairment Start Cheap Cholinesterase Inhibitors Side Effects? Combination with other strong anti cholinergics Specific Cases Severe Hepatic Failure Dialysis Beta 3 agonists Mirabegron Solabegron Beta adrenergics Beta adrenergics Beta 3 agonists Beta 3 agonists Mirabegron Mirabegron Solabegron Not yet approved in US Mechanism of Action Beta 3 agonsim Relaxes detrusor muscle Data Similar to About 20% response Side Effects Increase in BP Headache Dizziness Tachycardia GI upset NO: dry mouth, blurry vision 7
Answer 4 Caution in: Cognitive Impairment Start Cheap Cholinesterase Inhibitors Side Effects? Combination with other strong anti cholinergics Specific Cases Severe Hepatic Failure Dialysis Mirabegron? a. Mirabegron (Myrbetriq) 25mg po daily b. Solabegron mg po daily c. Oxybutynin (Ditropan) 5mg po daily d. Trospium (Sanctura) 60mg po daily References Ellsworth PI. The Pharmacologic Management of Idiopathic Overactive Bladder in Primary Care. J Fam Pract 2014;63:S38. Goode PS. Incontinence in Older Women. JAMA 2010;303:2172. Hoffman BL. Williams Gynecology, 2e. The McGraw Hill Companies, Inc. 2012. Imran M. Mirabegron for overactive bladder: a novel, first in class B3 agonist therapy. Urol J 2013 Sep 26;10(3):935 40. Marinkovic SP. The management of overactive bladder syndrome. BMJ 2012;344:32356. Nygaard I. Idiopathic Urgency Urinary Incontinence. N Engl J Med 2010; 363:1156. Nishizawa O. Guidelines for management of urinary incontinence. Int J Uro 2008;15:857. Qaseem A. Nonsurgical management of urinary incontinence in women: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2014;161:429 440. Shamliyan T. Systematic Review: Randomized, Controlled Trials of Nonsurgical Treatments for Urinary Incontinence in Women. Ann Intern Med 2008;148:459. Shamliyan T. Benefits and Harms of Pharmacologic Treatment for Urinary Incontinence in Women. Ann Intern Med 2012;156:861. Wu J. Prevalence and Trends of Symptomatic Pelvic Floor Disorders in US women. Obstet Gyncol 2014;123:141. 8