Urine for a treat (sorry) Jamie McCarrell, Pharm.D., BCPS, BCGP

URINARY INCONTINENCE www.medicaldaily.com

Learning Objectives Given a patient case, create an appropriate treatment plan for a patient with each of the following: Urge urinary incontinence (UUI) Stress urinary incontinence (SUI) Overflow incontinence (OI) Identify common side effects of the medications used to treat incontinence

UI Prevalence Under-reported Documented Rates of Incontinence 59% of affected delay reporting for 1 year or more 25% delay reporting for over 5 years Documented Rates of Incontinence 43-60% in nursing homes 35% in the acute care setting 8-34% in the community Increasing rates with increasing age M=F for overactive bladder (OAB) – 16% Higher rates of OAB with incontinence in women

Impact of UI Quality of Life Health Utilities Index (HUI) scoring* Health-related Quality of Life (HRQL)**  healthcare seeking behaviors  HRQL, mental health, work productivity Overwhelmingly negative ALZ UI 0.0 1.0 Dead Perfect Health Stroke *Bartoli S, et al. Urology. 2010;75:491-501. **Coyne KS, et al. BJU Int. 2011;108:1459-1471.

Urinary Incontinence Classification Overactive bladder (OAB) Detrusor contracts during filling phase Urge Urinary Incontinence Urethra or urethral sphincters cannot sufficiently impede urine flow Stress Urinary Incontinence Combination of UUI and SUI Mixed Bladder underactivity Bladder outlet obstruction (BOO) Overflow Incontinence Unrelated to urethral or bladder capability Functional

Urinary Incontinence Classification www.sketchymedicine.com

Causes and Precipitating Factors UUI (Myogenic versus neurogenic) Idiopathic Increasing age Neurologic disorders BOO Hysterectomy Recurrent UTIs SUI Pregnancy Childbirth (vaginal delivery) Menopause Cognitive impairment Obesity OI Bladder underactivity Functional Many, but not intrinsic damage to or malfunction of the urinary tract Myogenic – the overactive bladder and UUI result from changes within the smooth muscle of the bladder wall itself Neurogenic – ascribes the condition to disease related changes within the central or peripheral nervous systems.

Urge Urinary Incontinence Overactive bladder (OAB) Symptoms Urinary frequency (more then 8 times/day) and urgency (sudden compelling desire to urinate that is difficult to delay) Nocturia (>1 micturition/night) and/or enuresis (nocturnal incontinence) Volume usually large due to complete emptying of the bladder

Stress Urinary Incontinence Urethral/internal sphincter underactivity Symptoms: UI during activities that increase the intraabdominal pressure Running, coughing, sneezing, lifting Usually small volume, proportional to the level of activity

Overflow Incontinence Bladder is filled to capacity, but unable to empty Bladder underactivity Loss of function of the detrusor muscle Bladder outlet obstruction BPH, prostate cancer, diabetes, denervation Symptoms Difficulty initiating stream Dribbling Small amounts of urine leaking constantly

Nonpharmacologic Management Lifestyle modifications Weight loss improved mixed UI in obese women Scheduling regimens – bladder training, etc. Low quality evidence showed improvement in UUI Dementia Social implications Pelvic floor muscle rehabilitation >5 times as effective as no active treatment in improving SUI Anti-incontinence devices/agents Incontinence supplies Surgery

Incontinence Supplies Briefs, pads, various undergarments Tons to choose from, combine, etc for optimal protection Note – most Rx therapy will NOT restore continence, so these may be needed along with therapy Two things to cause Dr. McCarrell to become angry: “Diapers” Skin Integrity lose his

Summary of ACP Recommendations Non-Pharm UUI Bladder Training Weight Loss if Obese Pharmacologic Treatment Drug choice patient-specific SUI Pelvic Floor Muscle Training No Systemic Pharmacologic Therapy Potentially topical estrogens Mixed UI WITH

Pharmacologic Options for UI UUI Solifenacin Festerodine Trospium chloride Oxybutynin Tolterodine Darifenacin Mirabegron SUI Duloxetine Pseudoephedrine Ephedrine Estrogen (topical OI Bladder underactivity Self-catheterization Bladder outlet obstruction (BOO) Relieve the Obstruction

UUI Treatment Target Muscarinic Control Diagram: www.medscape.com

Urge Urinary Incontinence Treatment Anticholinergic agents/antispasmodics Mechanism of action Antagonize muscarinic cholinergic receptors Decrease parasympathetic nerve impulses to the detrusor muscle First-line pharmacotherapy – improved quality of life Agent within class chosen based on side effects and cost (as well as other considerations). Most effective agents for suppression of premature detrusor contractions, enhancing bladder storage, and relieving symptoms Adverse Effects: orthostatic hypotension, sedation, weight gain, dry mouth, constipation, confusion, hallucinations, tachycardia

Urge Urinary Incontinence Treatment Beta3 Agonist Mechanism of action Increases bladder storage capacity by activating beta-3 receptors and causing relaxation of the detrusor muscle Newest class of medications for UUI Consider for use in those intolerant of anticholinergic effects Adverse effects: high blood pressure, tachycardia

Urge Urinary Incontinence Medications Source: Lexi-Comp Medication MOA Dosing Comments Toviaz® Fesoterodine Antimuscarinic 4 mg PO daily (can ↑ to 8 mg) M3 preferred, $$$ Vesicare® Solifenacin 5 mg PO daily (can ↑ to 10 mg) Enablex® Darifenacin 7.5 mg PO daily (can ↑ to 15 mg) M3 specific, $$$ Sactura® Trospium IR: 20 mg BID ER: 60 mg daily 1st semi-specific to be generic Detrol® Tolterodine IR: 2 mg BID ER: 4 mg daily Can reduce dose if SEs Ditropan® Oxybutynin IR: 5 mg 2-3x/d ER: 5-10mg daily TD: 3.9 mg Q3-4d Gel: 3 pumps daily Most SEs, many formulations, less cost Myrbetriq® Mirabegron Beta-3 agonist 25 mg PO daily (can ↑ to 50 mg) Potential for less SEs, $$$, still really new

Oxytrol® For Women Median episodes of daily UI episodes Baseline: Transdermal oxybutynin 3.9 mg/day—4.0, placebo—4.0; 
 Week 12: Transdermal oxybutynin 3.9mg/day—1.0, placebo—2.0. 39% of women with OAB don’t want to discuss their condition with anyone 33% have not discussed their condition with a healthcare professional (HCP) Women typically have OAB for 4 years before talking to an HCP about it www.oxytrolforwomen.com

Urge Urinary Incontinence Treatment Tricyclic antidepressants Reserved for those with a concurrent indication Peripheral neuropathy, depression No more effective than oxybutynin IR Adverse effects: orthostatic hypotension, cardiac conduction abnormalities, confusion Overdose – potentially life-threatening Desipramine and nortriptyline preferred due to ↓ side effects

Pharmacologic Options for UI UUI Solifenacin Festerodine Trospium chloride Oxybutynin Tolterodine Darifenacin Mirabegron SUI Duloxetine Pseudoephedrine Ephedrine Estrogen (topical) OI Bladder underactivity Self-catheterization Bladder outlet obstruction (BOO) Relieve the Obstruction

SUI Treatment Target Adrenergic Control Non-Pharm Control Diagram: www.medscape.com

Stress Urinary Incontinence Treatment ACP guidelines recommend against treatment with pharmacologic therapy Strong recommendation, low-quality evidence Duloxetine (Cymbalta) First-line therapy in EAU guidelines, with moderate benefit Serotonin and norepinephrine have positive effects neuronal pathways of the micturition reflex Dosing: 40 mg PO BID Adverse effects: nausea, headache, insomnia Diminish with time

Stress Urinary Incontinence Treatment Alpha-adrenergic agonists Pseudoephedrine 15-60 mg TID Phenylephrine 10 mg four times daily Benefit in mild or moderate SUI Adverse effects: hypertension, headache, insomnia Topical Estrogens SUI in combination with urethritis or vaginitis due to estrogen deficiency

Pharmacologic Options for UI UUI Solifenacin Festerodine Trospium chloride Oxybutynin Tolterodine Darifenacin Mirabegron SUI Duloxetine Pseudoephedrine Ephedrine Phenylpropanolamine Estrogen (topical OI Bladder underactivity Self-catheterization Bladder outlet obstruction (BOO) Relieve the Obstruction

OI Treatment Target Muscarinic Overload Physical Block (Prostate?) Diagram: www.medscape.com

Overflow Incontinence Bladder underactivity Intermittent self-catheterization 3-4 times daily Bethanechol 25-50 mg PO 3-4 times/day Cholinergic agonist Short term use only Avoid in asthma or heart disease Remove anticholinergic agents Bladder outlet obstruction (BOO) Relief of the obstruction Can be pharmacological – see treatment of benign prostatic hyperplasia

As you treat, prevent these: Pendulum of Pee Teeter Totter of Tinkle Boomerang Bladder

Patient Case TT is an 92 yo female who presents with complaints of urinary frequency (12x/24 h), urgency, and incontinence. She reports incontinence to occur 1-3 x/24 h, and is now wearing absorbent briefs. What questions do you have for her?

Patient Case Continued Leakage is not worsened by laughing, coughing, sneezing, or carrying heavy objects. She denies feelings of incomplete voiding. She is embarrassed, and has decreased her social activities significantly. Non-pharmacological approaches have failed.

Asymptomatic Bacteriuria www.medicaldaily.com

Asymptomatic Bacteriuria > 70 y.o. 15-20% prevalence for community, 25-50% prevalence for nursing home Diagnosis: WOMEN: 2 consec (+) cultures with ≥ 105 cfu/mL MEN: Single, clean catch specimen with ≥ 105 cfu/mL CATH: Single specimen with ≥ 105 cfu/mL Potentially 102 if “in and out” and not biofilm Should not be treated (unless UTI symptoms)

Asymptomatic Bacteriuria 2019 IDSA Guidelines Screening for or treatment of asymptomatic bacteriuria is not recommended for the following persons. Healthy, non-pregnant women Pediatrics Older persons living in the community Older persons in LTCFs Diabetic men and women Solid organ (including renal) transplant Spinal cord injury Indwelling urinary catheter Non-urologic surgery

Determination of UTI 2019 Guidelines – No help with biomarkers McGeer Criteria for NH residents (developed 1991) Supported by: Association for Professionals in Infection Control (APIC) and the Society for Healthcare Epidemiology of America (SHEA) Also supported by CMS and DHHS 30% sensitive, 82% specific Loeb Criteria for NH residents (developed 2001) No “official” support 19% sensitive, 89% specific

Determination of UTI No Catheter Yes Catheter McGeer Criteria 3 Must Be Present Yes Catheter 2 Must Be Present Fever > 100 F or chills New or increased burning w/urine New flank pain Changes to urine properties Mental function decline

Determination of UTI Loeb Criteria Must have fever > 100 F or > 2.4 F above baseline AND one of the following (new or worsening): Urgency Frequency Suprapubic pain Gross hematuria Costovertebral angle tenderness Urinary incontinence

Cortes-Penfield, et al (2017)

Urine for a treat (still sorry) Jamie McCarrell, Pharm.D., BCPS, BCGP