Trospium

Details regarding the pharmacokinetics, contraindica-tions/precautions, and dosing of the five recommended agents (oxybutynin, tolterodine, trospium chloride, solifenacin, and darifenacin) are illustrated in Table 50-3.7 12,14 16 A current clinical controversy is which of these agents should be considered first-line in UUI, and in the case of oxybutynin and... 

Parameter Oxybutynin Tolterodine Trospium chloride Solifenacin Darifenacin... 

Guay DRP. Trospium chloride an update on a quaternary anticholinergic for the treatment of urge urinary incontinence. Ther Clin Risk Manag 2005 1 157-166. 

Trospium chloride, a quaternary ammonium drug (Fig. 7.45), appears to be a substrate of P-gp, and it can be taken up by cells quicky [597]. The evidence for transmembrane diffusion appears substantial. The molecule is very soluble in water (>50 mg/mL), but not in lipids (9.2 pg/mL in mineral oil) the octanol-water log Kp is —1.22 [598]. The human intestinal absorption (HIA) is 11% the molecule is not metabolized. In cell intestinal patch uptake studies, trospium is absorbed from a... 

Overactive bladder Anticholinergic agentyantispas-modics Oxybulynin TDS (5.9 mg/day apply one patch twice weekly), tolterodine IR (1-2 mg twice daily), tolterodine LA (2-4 mg daily), trospium chloride (20 mg once or twice daily), solifenacin (5-10 mg daily), darifenacin (7.5-15 mg daily) Anticholinergics are first-line drug therapy (oxybulynin or tolterodine is preferred). 

Trospium chloride, a quaternary ammonium anticholinergic, is superior to placebo and is equivalent to oxybutynin IR and tolterodine IR. However, clinical studies are limited by their focus on cystometric rather than clinical endpoints, small absolute benefits compared with placebo, and lack of comparisons with LR formulations. 

Trospium chloride causes the expected anticholinergic adverse effects with increased frequency in patients >75 years old. 

TROSPIUM CHLORIDE The recommended dose is 20 mg twice daily. Dose at least 1 hour before meals or give on an empty stomach. 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

Distribution - Protein binding ranged from 50% to 85% when therapeutic concentration levels (0.5 to 50 ng/mL) were incubated with human serum in vitro. The majority of trospium is distributed in plasma. The apparent volume of distribution for a 20 mg oral dose is 395 ( 140) L. 

Metabolism - The metabolic pathway of trospium in humans has not been fully defined. Of the 10% of the dose absorbed, metabolites account for approximately 40% of the excreted dose following oral administration. The major metabolic pathway is hypothesized as ester hydrolysis with subsequent conjugation of benzylic acid to form azoniaspironortropanol with glucuronic acid. Cytochrome P450 is not expected to contribute significantly to the elimination of trospium. 

Excretion - The plasma half-life for trospium following oral administration is approximately 20 hours. After administration of oral trospium, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8%) was recovered in urine 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29.07 L/h) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that also are renally eliminated. 

Gender Studies comparing the pharmacokinetics in different genders had conflicting results. When a single 40 mg trospium dose was administered to 16 elderly subjects, exposure was 45% lower in elderly females compared with elderly males. When 20 mg trospium was dosed twice daily for 4 days to 6 elderly males and 6 elderly females (60 to 75 years of age), AUC and Cmax were 26% and 68% higher, respectively, in females without hormone... 

Renal function impairment Severe renal impairment significantly altered the disposition of trospium. A 4.5-fold and 2-fold increase in mean AUCo- and Cmax. respectively, and the appearance of an additional elimination phase with a long half-life (approximately 33 hours) was detected in... 

Renai function impairment Dose modification is recommended in patients with severe renal insufficiency (Ccr less than 30 mL/min). In such patients, administer trospium as 20 mg once daily at bedtime. 

Hepatic function impairment Use caution when administering trospium in patients with moderate or severe hepatic dysfunction. 

Eideriy In 2 studies, the incidence of commonly reported anticholinergic adverse events in patients treated with trospium (including dry mouth, constipation, dyspepsia, UTI, and urinary retention) was higher in patients 75 years of age and older as compared with younger patients. This effect may be related to an enhanced sensitivity to anticholinergic agents in this patient population. 

Lactation Trospium (2 mg/kg orally and 50 mcg/kg IV) was excreted, to a limited extent (less than 1%), into the milk of lactating rats. It is not known whether this drug is excreted in human milk. Exercise caution when administering trospium to a nursing mother. Use during lactation only if the potential benefit justifies the potential risk to the newborn. 

Card/ac e/fecfs Asymptomatic, nonspecific T-wave inversions were observed in 1 study more often in subjects receiving trospium than in subjects receiving moxifloxacin or placebo following 5 days of treatment. This finding was not observed during routine safety monitoring in 2 other placebo-controlled clinical trials in 591 trospium-treated overactive bladder patients. The clinical significance of T-wave inversion in this study is unknown. 

Narrow-angle glaucoma In patients being treated for narrow-angle glaucoma, only use trospium if the potential benefits outweigh the risks and, in that circumstance, only with careful monitoring. 

Risk of urinary retention Administer trospium with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. 

Drugs that may affect trospium include other anticholinergic agents drugs eliminated by active tubular secretion. 

Drugs that may be affected by trospium include those eliminated by active tubular secretion (eg, digoxin, procainamide, pancuronium, morphine, vancomycin, metformin, and tenofovir). 

Drug/Food interactions It is recommended that trospium be taken at least 1 hour prior to meals or on an empty stomach. 

The three most common adverse events reported by patients receiving 20 mg trospium twice daily were dry mouth, constipation, and headache. 

Studies have not shown that trospium is better than generically available drugs for the same purpose... 

Do not take trospium with high-fat meals because they may reduce drug absorption... 

Trospium chloride another anticholinergic for overactive bladder. Med Let 2004 46 63-64. 

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