Trospium chloride: an update on a quaternary anticholinergic for treatment of urge urinary incontinence

Abstract

Trospium chloride is a quaternary ammonium compound, which is a competitive antagonist at muscarinic cholinergic receptors. Preclinical studies using porcine and human detrusor muscle strips demonstrated that trospium chloride was many-fold more potent than oxybutynin and tolterodine in inhibiting contractile responses to carbachol and electrical stimulation. The drug is poorly bioavailable orally (< 10%) and food reduces absorption by 70%-80%. It is predominantly eliminated renally as unchanged compound. Trospium chloride, dosed 20 mg twice daily, is significantly superior to placebo in improving cystometric parameters, reducing urinary frequency, reducing incontinence episodes, and increasing urine volume per micturition. In active-controlled trials, trospium chloride was at least equivalent to immediate-release formulations of oxybutynin and tolterodine in efficacy and tolerability. The most problematic adverse effects of trospium chloride are the anticholinergic effects of dry mouth and constipation. Comparative efficacy/tolerability data with long-acting formulations of oxybutynin and tolterodine as well as other anticholinergics such as solifenacin and darifenacin are not available. On the basis of available data, trospium chloride does not appear to be a substantial advance upon existing anticholinergics in the management of urge urinary incontinence.

Efficacy and Safety of Propiverine Chloride Flexible Dose in Female Mixed Urinary Incontinence Patients

“…Anticholinergic therapy is often used as a reversible firstline treatment option for patients with mixed urinary incontinence, which is one of the common medical treatments for reducing bladder hypersensitivity. Thus anticholinergic drugs had been used for the patient with urge incontinence as a result of involuntary bladder contractions [13,14]. Propiverine is one of the useful medications for both stress incontinence and mixed urinary incontinence [5].…”

Anticholinergiques et hyperactivité vésicale

“…Une surveillance par électrocar-diogramme s'impose chez les sujets âgés et traités pendant une longue durée. Le chlorure de trospium est contre-indiqué en cas de glaucome à angle fermé 45,44 . La posologie usuelle est de 20 mg, 2 fois par jour, pris au moins 1 heure avant les repas ou à jeun.…”

“…Pour les formulations à libération prolongée, la posologie recommandée est de 60 mg/jour à raison d'une prise unique. Cette dose doit être réduite de 50 % en cas d'insuffisance rénale (clairance de la créatinine < 30 ml/min) et chez les patients âgés de plus de 75 ans 44 . Une étude a porté sur 329 patients ayant reçu du chlorure de trospium ou un placebo pendant 12 semaines.…”

Cardiac effects of muscarinic receptor antagonists used for voiding dysfunction

“…No ECG effects occurred at any dose except a 10 to 40 ms reduction in the QT interval due to the tachycardia [93]. In a study of the possible QT effects of the drug (see below), trospium caused, compared with placebo, a mean increase in HR of 9.1 beats min −1 for the 20 mg dose and 18.0 beats min −1 for the 100 mg dose [94]. In two U.S. placebo‐controlled trials in patients with OAB, the mean increase in HR compared with placebo in one study was observed to be 3.0 and in the other 4.0 beats min −1 [95, 96].…”