Trospium chloride is an antimuscarinic drug licensed for the treatment of detrusor instability or detrusor hyperreflexia with the symptoms of urinary frequency, urgency, and urge incontinence. • It is as effective as oxybutynin in improving urodynamic values such as maximum bladder capacity and urinary volume. ……………………………………………………………………………………………. • Trospium is also as effective as tolterodine in reducing micturition frequency and more effective than tolterodine in reducing episodes of incontinence. • It is as well tolerated as tolterodine and better tolerated than oxybutynin.
CNS side effects are unlikely since the drug does not penetrate the blood-brain barrier. ………………………………………. • Trospium is less expensive than tolterodine or propiverine, but more expensive than oxybutynin. It offers a less expensive alternative to tolterodine when oxybutynin cannot be tolerated. • Further information is required from randomised clinical trials of the effects on quality of life. Date Published: February 2002 Monograph Number: 04/02/01 Marketed; October 2000 Region of origin to whom queries should be directed: South West (Southampton) The information contained in this document will be superseded in due course.
Not to be used for commercial purposes Copyright MIPG 2002 Web site http://www. ukmi. nhs. uk/Med_info/stage4. html TROSPIUM Approved Name: Brand Name: (Manufacturer): Presentation: BNF Therapeutic Class: Licensed Indications: Dosage and Administration: Trospium (not to chlordiazepoxide). Regurin (Galen Ltd. ) be confused with Tropium, a brand of Tablets containing trospium chloride 20mg. Drugs for urinary frequency, enuresis, and incontinence (BNF 7. 4. 2) The treatment of detrusor instability or detrusor hyperreflexia with the symptoms of urinary frequency, urgency, and urge incontinence.
Adults only. 20mg twice daily, swallowed whole, with a glass of water, before meals on an empty stomach. The need for continuous treatment should be reassessed at regular intervals of 3-6 months. In severe renal impairment 20mg once daily or every second day. (see SPC) Hospital [Y] Primary Care [Y] Sector of Use: Therapeutic Comment: Trospium is a new antimuscarinic which may be considered an nd alternative 2 line drug when oxybutynin cannot be tolerated. Cost and Course Details: Cost of 28 days therapy (MIMS Jan 2002) Trospium 20mg twice daily ? 23. 33
Treatment Alternatives: MIMS Jan 2002 Oxybutynin (Ditropan) 2. 5mg bd to 5mg qds Oxybutynin m/r (Ditropan XL) 5mg to 30mg daily Propiverine 15 mg bd-tds Tolterodine 2mg bd ?4. 57 – ? 17. 79 ? 8. 86 – ? 53. 14 ? 30. 56 – ? 45. 84 ? 30. 56 Page 2 of 7 TROSPIUM INTRODUCTION Urinary incontinence is a major problem especially in elderly patients. The prevalence of “frequent Most of the drug is excreted unchanged by the kidneys, though a small amount appears as the spiroalcohol, a metabolite formed by ester hydrolysis. ………………… bioavailability of a single dose is 9. 6 ± 4. 5%.
Simultaneous intake of food reduces the bioavailability. incontinence” or “bothersome incontinence” in women over 65 years is reported to be 10-30%. Men suffer less frequently from urinary incontinence than women with the overall prevalence ranging from 2-3%. Terminal elimination half-life is 10-20 hours. Plasma Urge incontinence is the most common form of incontinence. It is related to an overactive detrusor and means the involuntary loss of urine accompanied by an urge which is usually felt as imperative. It requires treatment that aims at reducing spontaneous detrusor contractions.
Antimuscarinic drugs (oxybutynin, There are no significant differences in the elderly, but mean AUC was four fold higher, maximum serum levels two fold higher, and mean half life was prolonged in patients with severe renal impairment [2,5]. ………. protein binding is 50-80%. ………………………………. propiverine, tolterodine, and flavoxate) are the main form of treatment [1]. Trospium chloride has negligible inhibitory effects on CYP3A4, CYP1A2, CYP2E1, CYP2C19, CYP2C9 and PHARMACOLOGY Trospium is an antimuscarinic drug with high affinity to muscarinic receptors M1, M2, and M3 with negligible affinity to nicotinic receptors.
It diminishes the CYP2A6, but is a reasonably potent inhibitor of CYP2D6 in vitro [6]. EFFICACY (see Table 1 for details of trials). Trospium has been shown to be significantly more effective than placebo at improving urodynamic values in patients with detrusor instability and urinary urge syndrome. contractile tone of smooth muscle in the genito-urinary tract [1,2]. …………………………………………………… Trospium also inhibits gastric acid secretion and gastric motility [3], inhibits the secretion of bronchial mucus, saliva and sweat, and affects ocular accommodation [1].
However, trospium produces significantly less effects on the EEG compared to oxybutynin and should be less likely to produce central nervous system effects [4]. Due to its low lipophilicity trospium hardly crosses the blood brain barrier (unlike tolterodine and oxybutynin) [1]. Two randomised double-blind trials in such patients found trospium 200mg bd significantly increased bladder capacity and urinary volume at first unstable contraction compared to placebo over a three week period [7,9]. However, one of these trials had a high rate of withdrawal and protocol violation. PHARMACOKINETICS.
After oral administration of trospium chloride, peak plasma levels are achieved at 4-6 hours . Absolute A further trial in 61 patients with spinal cord injuries and detrusor hyperreflexia showed that trospium was significantly more effective than placebo in improving Page 3 of 7 TROSPIUM maximum bladder capacity and decreasing maximum detrusor pressure [8]. ………………………………….. … ……………………………….. In comparative trials trospium has been shown to be as effective as oxybutynin. …………………………………… Trospium 20mg bd Oxybutynin 5mg bd (n=268) (n=90) % patients reporting adverse effects 64. 8 76.
7 % patients reporting dry mouth 33 50 % patients reporting gastrointestinal effects 39 51 % patients where investigator’s assessment of tolerability was very good 63 42 ADVERSE EFFECTS Trospium is well tolerated. In a 12 month study designed to investigate the long term tolerability and safety of trospium, the following were reported [13]. In a double blind randomised trial in 95 patients with spinal cord injuries and detrusor hyperreflexia trospium 20mg bd was as effective as oxybutynin 5mg tds over three weeks in improving maximum bladder capacity and decreasing maximum detrusor pressure [10].
In a double blind trial in 67 patients with hyperactive neurogenic bladder, trospium was compared with oxybutynin over three weeks [11]. The two drugs produced similar beneficial effects on maximum bladder capacity, maximum voiding detrusor pressure, and improvement in compliance. This study was reported as an abstract. ………………………………………………. All differences between the two treatments were statistically significant . …………………………….. In a study comparing trospium 20mg bd with tolterodine 2mg bd, the two drugs had comparable adverse effect.
In a further double blind randomised multicentre trial in 232 patients with urge syndrome, trospium 20mg bd was compared with tolterodine 2mg bd or placebo for three weeks. Trospium was at least as effective as tolterodine in reducing micturition frequency in 24 hours and in increasing the mean volume per voiding. Trospium was more effective in reducing episodes of incontinence [12]. Again, this study was reported as an abstract. profiles: 25 of 76 patients on trospium reported adverse effects compared to 25 of 77 on tolterodine and 12 of 79 on placebo.
Dry mouth was reported in 21 patients on trospium, 22 patients on tolterodine, and 6 on placebo [12]. Thus the incidence of adverse effects, particularly dry mouth, in patients on trospium is less than those on oxybutynin, but similar to those on tolterodine. In a long term double blind study over one year trospium 20mg bd was as effective as oxybutynin 5mg bd in increasing bladder capacity and urinary volume [13]. The Summary of Product Characteristics reports undesirable effects as: Common (>1%) dry mouth, dyspepsia, constipation, abdominal pain, nausea.