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Continence Coach: Treating Overactive Bladder: A New Tool in Your Toolkit
Considering the wide choice of prescription drugs on the market for overactive bladder (OAB) symptoms of urge urinary incontinence, urgency, and urinary frequency, one might wonder why yet another has received US Food and Drug Administration (FDA) clearance. Late June 2012, Astellas Pharma US, Inc (Northbrook, IL), a US subsidiary of Tokyo-based Astellas Pharma Inc, announced FDA approval of Myrbetriq™ (mirabegron) extended-release tablets for the treatment of OAB. Allowing time for filling pipelines to pharmacies, the drug should be generally available by year’s end 2012. The announcement is especially important because mirabegron is the first oral OAB treatment with a distinctly different mechanism of action from the other agents on the market, the first of which was introduced 30 years ago. Antimuscarinics have long comprised the pharmacologic treatment standard for OAB. Although the mechanisms by which antimuscarinics improve the symptoms of OAB are not yet fully understood by researchers, the primary mechanism of action is believed to be the drugs’ ability to block muscarinic receptors on the efferent nerves in the detrusor muscle and thus reduce the ability of the detrusor to contract, not so much for a significant reduction of the voiding contraction itself.1 Mirabegron, on the other hand, works by relaxing the detrusor smooth muscle during the storage phase by acting on beta-3 adrenergic receptors, producing the effect of increasing bladder capacity.2 Much of this discovery builds on investigations conducted more than 15 years ago, largely by Brading and Turner.3 This suggests the possibility of using combination drugs to achieve even greater effectiveness in reducing symptoms, both quieting the bladder contractions and extending the filling cycle. Until future research determines the possibilities and safety considerations for such a protocol, mirabegron should be administered with caution to patients taking antimuscarinic medications for the treatment of OAB or with clinically significant bladder outlet obstruction contributing to urinary retention.
Safety Considerations and Side Effects
Mirabegron has been studied in more than 10,000 individuals to date; its FDA approval was based on safety and efficacy data from three placebo-controlled Phase 3 studies by Astellas in which the drug, at both approved dosage levels of 25 mg and 50 mg once daily, resulted in statistically significant improvement in efficacy parameters of incontinence episodes and voiding frequency.4 The most commonly reported adverse reactions (>2% of mirabegron patients and greater than placebo) were hypertension, nasopharyngitis, urinary tract infection, and headache.4 Consequently, periodic blood pressure assessment is recommended, especially in hypertensive patients.
Nationwide research by the National Association For Continence (NAFC) has documented abounding frustration among those in treatment for OAB. For example, in one study5 conducted among 400 middle age women ages 40 to 65 years, 351 (almost nine out of 10, 88%) had treated or were currently treating their OAB with medication. Of those in current treatment, 43 (fewer than one in four of 200; 22%) were satisfied with their current OAB medication treatment, and of those whose treatment had lapsed, 46 (almost one in four of 200; 23%) claimed they stopped medication because of undesirable side effects. Among this same subgroup of 200 lapsed treatment patients, 28% said the treatment options tried were too expensive.
In the NAFC’s earlier survey6 of the same age category of women, nearly one third (31%) of those classified as lapsed users of prescription OAB drugs reported they were more likely to complain to doctors about gastrointestinal problems than other undesirable effects. Interestingly, the most prevalent self-reported problem among baby boomers using OAB medication was dry skin. Because its alternative mode of action may mitigate gastrointestinal issues in patients prescribed an antimuscarinic, the new drug improves the variety of treatment options available in a provider’s toolkit.
Importance of an Accurate and Complete Diagnosis
Although the underlying cause of OAB is not entirely understood, an enlarged prostate in men can contribute to urinary urgency and frequency and thus complicate an accurate diagnosis. In women, a prolapsed bladder may result in difficulty emptying the bladder, creating the sensation they need to urinate. For others, a neurological obstacle, damage, or disease may interfere with signals between the brain and the lower urinary tract, causing what is called neurogenic bladder. For example, an early warning sign of multiple sclerosis can be urinary frequency. Bladder stones, polyps, or tumors can be the culprit behind frequency of urination, as can a urinary tract infection or ovarian cancer in women. A number of prescription drugs have a diuretic effect that contributes to frequency. The point is that a diagnosis needs to be complete and not stop at the superficial manifestation of classic OAB symptoms.
Remembering the Benefits of Combination Therapy
The most effective first-line treatment for OAB is not medication alone. Although no nutrition-based cure for incontinence is known, diet (including hydration) can have a profound effect on a person’s voiding patterns. Older patients already may have given up alcohol and caffeine, but clinicians should be mindful of artificial sweeteners as established causal agents. Older patients are also notorious for not drinking enough water; highly concentrated urine can be a bladder irritant, precipitating contractions. Pelvic muscle exercises are a central element of behavioral strategies to increase bladder control, to both reduce leakage and calm the urgent messages from the bladder. Structured bladder retraining can restore healthy patterns of voiding. Beyond behavioral strategies, Botox® (Allergan, Irvine, CA) is now approved for neurogenic bladder and percutaneous tibial nerve stimulation for individuals with urgency incontinence who have not responded to medical and/or behavioral treatment but are postponing a neuromodulation implant.
Your toolkit for helping your patients manage OAB has greatly expanded. Take advantage of the options and find what works for each patient individually.
Dr. Muller is the Executive Director, National Association For Continence (NAFC). The NAFC is a national, private, nonprofit organization dedicated to improving the quality of life of people with incontinence. The NAFC’s purpose is to be the leading source for public education and advocacy about the causes, prevention, diagnosis, treatments, and management alternatives for incontinence.
This article was not subject to the Ostomy Wound Management peer-review process.
1. Andersson KE. Antimuscarinics for treatment of overactive bladder. Lancet Neurol. 2004;3:46–53.
2. Yamaguchi O. Antimuscarinics and overactive bladder: other mechanism of action. Neurol Urodynam. 2010;29:112–115.
3. Brading AF, Turner WH. The unstable bladder: towards a common mechanism. Br J Urol. 1994;73:3–8.
4. Mirabegron (YM178) Advisory Committee Briefing Document, April 5, 2012. Available at: www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM298285.pdf. Accessed October 12, 2012.
5. Muller N. Overactive bladder in middle age women: the frustration of baby boomers with overactive bladder symptoms. Ann Urol. 2010;1(1):1–9.
6. Muller N. What Americans understand and how they are affected by bladder control problems: highlights of recent nationwide consumer research. Urolog Nurs. 2005;25(2):109–115.
