Clinical Therapeutics/Volume 27, Number 5, 2005 New Drug Trospium Chloride for the Treatment of Overactive Bladder with Urge Incontinence Devada Singh-Franco, PharmD; Caridad Machado, PharmD; Sony Tuteja, PharmD, BCPS; and Antonia Zapantis, MS, PharmD Pharmacy Practice, Nova Southeastern University, Fort Lauderdale, Florida ABSTRACT Background: Urinary incontinence is caused by an overactive bladder, leading to symptoms of urgency, frequency, and incontinence. Urge incontinence occurs predominantly in women as they age. Objectives: This article reviews the current primary literature concerning the efficacy and tolerability of the anticholinergic agent trospium chloride (TC1) in the treatment of overactive bladder with symptoms of urge incontinence, urgency, and frequency. The phar- macokinetics of TC1 are also reviewed. Methods: Pertinent articles in English were identified through a search of MEDLINE (1966-present), EMBASE Drugs & Pharmacology (1980-third quarter 2004), Cur- rent Contents/Clinical Medicine (week 42, 2003-week 41, 2004), Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder urinary incontinence, trospium, randomized controlled clinical trial, oxybu- tynin, tolterodine, scopolamine, imipramine, desipra- mine, and propanthetine. Results: TCI, a quaternary amine, exhibits high solu- bility in water but low oral bioavailability (9.6%) and poor central nervous system penetration. Approxi- mately 80% of the absorbed fraction is renally elimi- nated as unchanged drug via active tubular secretion, with -15% hepatically metabolized into a spiroalco- hol and hydrolysis/oxidation products. In 3 placebo- controlled studies, patients who received TC1 had an in- crease in maximum bladder filling capacity and bladder compliance, with a reduction in maximum cystometric capacity (P < 0.005); however, only 1 of these studies showed an increase in bladder compliance, with reduc- tions in maximum detrusor pressure (P < 0.001), num- ber of voids/d (P < 0.001), and incontinence episodes/d (P < 0.001). In another placebo-controlled study, TCI reduced the number of voids/d and incontinence episodes/d (both, P < 0.001). In 2 double-blind studies, TCI and oxybutynin were similarly effective in signifi- cantly increasing maximum cystometric capacity and bladder compliance, and in significantly reducing maxi- mum detrusor pressure compared with baseline (all, P < 0.001); there were no significant differences be- tween the 2 treatments at end point. In a third double- blind study comparing TCI and tolterodine with placebo, only TC1 significantly reduced the frequency of micturitions/d (P = 0.01). Commonly reported adverse effects in patients receiving TC1 included dry mouth, constipation, and headache. Conclusions: In the 7 studies reviewed, TC1 was ef- fective and well tolerated in patients with urge inconti- nence caused by idiopathic detrusor muscle overactivity or neurogenic detrusor overactivity resulting from spinal cord injury. However, this agent was associated with anticholinergic adverse effects similar to those of other anticholinergic agents; careful monitoring of tolerability is required. (Ctin Tber. 2005;27:511-53 O) Copyright © 2005 Excerpta Medica, Inc. Key words: urinary incontinence, trospium, tros- pium and pharmacokinetics, trospium and placebo, trospium and oxybutynin, trospium and tolterodine. INTRODUCTION The 2nd International Consukation on Incontinence defined urinary incontinence as an involuntary loss of urine. 1 There are a number of pharmacologic therapies Accepted~r publicationMarch4, 2005. do i: 10.1016/j. cli nthera.2005.0S. 008 0149 2918/05/$19.00 Printed in the USA. Reproductionin wholeor part is not permitted. Copyright © 200S Excerpta Medica, Inc. May 2005 511