Trospium Chloride Treatment of Overactive Bladder

Abstract

Objective: To review the pharmacology, pharmacokinetics, safety, and clinical application of trospium chloride for the management of overactive bladder (OAB). Data Sources: Clinical literature including both primary sources and review articles was accessed through MEDLINE, International Pharmaceutical Abstracts, and Cochrane databases from 1980 through January 8, 2009. Search terms included overactive bladder, urge urinary incontinence, muscarinic receptor antagonists, and urinary frequency. Further data sources were identified from bibliographies of selected articles. Study Selection and Data Extraction: Basic pharmacology data were extracted from animal studies and pharmacokinetic data were gathered from human studies. Multicenter, parallel, randomized, double-blind, placebo-controlled studies were included to describe the efficacy and adverse effects of trospium. Data Synthesis: Trospium chloride is an antimuscarinic agent indicated for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency. Trospium has 3 chemical and pharmacokinetic properties unique among antimuscarinic agents: it is a positively charged quaternary ammonium compound with minimal central nervous system penetration; it is not metabolized by the cytochrome P450 system, resulting in a lower tendency for drug interactions; and it is excreted mainly unchanged in the urine as the active parent compound, providing local activity to achieve early onset of clinical effect and prolonged efficacy. In two 12-week, randomized, placebo-controlled clinical studies in adults with OAB, trospium 20 mg twice daily was more effective than placebo in reducing the number of micturitions per 24 hours, reducing the number of urge incontinence episodes per week, and increasing the volume of urine voided per micturition. Placebo-controlled trials report efficacy with trospium in treatment of OAB; comparative trials with other anticholinergic agents are limited. Current therapy of OAB consists primarily of anticholinergic drugs such as oxybutynin, which are associated with therapy-limiting adverse effects. Because the prevalence of OAB is greatest among the elderly, safety considerations regarding renal function must be noted, with dosage adjustment required in patients with severe renal impairment. Conclusions: Whether the pharmacodynamic properties of trospium make it superior to other therapies will require considerable additional experience with the drug. For now, it appears to be a feasible alternative for patients who cannot tolerate oxybutynin.