Trospium chloride for the treatment of overactive bladder with urge incontinence.
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.


OBJECTIVE
This article reviews the current primary literature concerning the efficacy and tolerability of the anticholinergic agent trospium chloride (TCl) in the treatment of overactive bladder with symptoms of urge incontinence, urgency, and frequency. The pharmacokinetics of TCl are also reviewed.


METHODS
Pertinent articles in English were identified through a search of MEDLINE (1966-present), EMBASE Drugs & Pharmacology (1980-third quarter 2004), Current 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, oxybutynin, tolterodine, scopolamine, imipramine, desipramine, and propantheline.


RESULTS
TCl, a quaternary amine, exhibits high solubility in water but low oral bioavailability (9.6%) and poor central nervous system penetration. Approximately 80% of the absorbed fraction is renally eliminated as unchanged drug via active tubular secretion, with approximately 15% hepatically metabolized into a spiroalcohol and hydrolysis/oxidation products. In 3 placebo-controlled studies, patients who received TCl had an increase 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 reductions in maximum detrusor pressure (P < 0.001), number of voids/d (P < or = 0.001), and incontinence episodes/d (P < or = 0.001). In another placebo-controlled study, TCl reduced the number of voids/d and incontinence episodes/d (both, P < or = 0.001). In 2 double-blind studies, TCl and oxybutynin were similarly effective in significantly increasing maximum cystometric capacity and bladder compliance, and in significantly reducing maximum detrusor pressure compared with baseline (all, P < 0.001); there were no significant differences between the 2 treatments at end point. In a third double-blind study comparing TCl and tolterodine with placebo, only TCl significantly reduced the frequency of micturitions/d (P = 0.01). Commonly reported adverse effects in patients receiving TCl included dry mouth, constipation, and headache.


CONCLUSIONS
In the 7 studies reviewed, TCl was effective and well tolerated in patients with urge incontinence 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.
Pharmacy Practice, Nova Southeastern University, Fort Lauderdale, FL 33328, USA. singh@nova.edu
Devada
D
Singh-Franco
Caridad
C
Machado
Sony
S
Tuteja
Antonia
A
Zapantis
D000375:Aging; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001561:Benzilates; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003408:Cresols / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017093:Liver Failure / Q000150:complications / Q000378:metabolism; D008297:Male; D008333:Mandelic Acids / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D009662:Nortropanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism; D000068737:Tolterodine Tartrate; D014549:Urinary Incontinence / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D001559:Benzhydryl Compounds; D001561:Benzilates; D018680:Cholinergic Antagonists; D003408:Cresols; D008333:Mandelic Acids; D009662:Nortropanes; C003330:trospium chloride; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin