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Trospium Chloride Tablets (SancturaTM)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
A new quaternary ammonium compound has been approved for the treatment of overactive bladder. Trospium is a nonselective antimuscarinic agent that reduces the tonus of smooth muscle in the bladder. It has been available in Europe for more than 20 years and is manufactured by Maduas AG in Germany and marketed in the United States as SancturaTM by Odyssey Pharmaceuticals Inc and Indevus Pharmaceuticals Inc.
Trospium is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.1
The recommended dose is 20 mg twice daily. It should be taken on an empty stomach or at least 1 hour before meals. Dosage modification is recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) and in geriatric patients 75 years or older. A 20 mg dose once daily is recommended for these patients.1
Trospium is available as 20 mg tablets.
Trospium does not appear to cross the blood brain barrier and does not affect CYP450 metabolism.1,2 In contrast, oxybutynin and tolterodine have potential drug-drug interactions with CYP3A4 and CYP2D6 respectively. About 60% of the absorbed drug is excreted unchanged in the urine and therefore a large percent is available to the bladder.1
Most common side effects associated with trospium are dry mouth (20.1% vs 5.6% for placebo) and constipation (9.6% vs 4.6%). Asymptomatic, non-specific T-wave inversions were observed more often than with placebo or moxifloxacin during electrophysiology studies. The clinical significance of this effect is not known.1
The approval of trospium is based on 2 US, placebo-controlled, 12-week studies in patients with overactive bladders (n = 523,648) and one 9-month open label extension.1 In the placebo-controlled studies, trospium showed a statistically significant decrease in mean urinary frequency and urge incontinence episodes.1,3 In addition, mean urinary void volume, voiding urge severity, and urination during day and night were improved compared to placebo. Improvements were also detected with the travel, social relationships, and emotional health subscales of the Incontinence Impact Questionnaire.3 In a long-term comparative tolerability and efficacy study (52 weeks) trospium (20 mg twice daily) was reported to be comparable in efficacy in terms of urodynamic variables to oxybutynin (5 mg twice daily) but better tolerated in terms of dry mouth symptoms.4 Similarly trospium (20 mg twice daily) was reported to be comparable to but better tolerated than oxybutynin (5 mg 3 times a day) in patients with spinal cord injury and detrusor hyper-reflexia.5 Trospium (20 mg twice daily) reported a greater decrease in frequency of mictuation per 24 hours compared to tolterodine (2 mg twice daily) with similar frequency of moderate-to-severe dry mouth (7% vs 9%).6 The price of trospium was not available at the time of this review.
Overactive bladder is characterized by urgency, urge urinary incontinence, frequency, or nocturia. About one-third of patients with overactive bladder have urge incontinence and two thirds do not. Urge incontinence is much more common in women.7 Antimuscarinics have been considered the mainstay of treatment for overactive bladder. Two recent reviews, however, suggest that the magnitude of clinical effect is small and of questionable clinical value.8,9 Antimuscarinic drugs generally seem to have similar efficacy but may differ in frequency of side effects. Since muscarinic receptor M3 subtypes that mediate cholinergic contraction of the detrusor muscles are found in the bladder and salivary gland, dry mouth is a common side effects associated with these drug. Different drug delivery systems have been developed to reduce this side effect, and in general, extended release formulations have a lower frequency compared to immediate release formulations.10,11 Extended release tolterodine (4 mg) appear to have a lower frequency of dry mouth than extended release oxybutynin (10 mg).12 Based mainly on indirect comparison, the frequencies appear similar between trospium and tolterodine extended release. Transdermal oxybutynin may have the lowest frequency of dry mouth but has a discontinuation rate of about 10% due mainly to application site reaction (eg, pruritus and erythema).13 It is not known how antimuscarinic drugs in general would compare to bladder retraining or how combination therapy would compare.8
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
1. SanctuaryTM Product Information. Odyssey Pharmaceutical Inc, May 2004.
2. Pak RW, et al. Curr Urol Rep. 2003;4(6):436-40.
3. Zinner N, et al. J Urol. 2004;171:2311-15.
4. Halaska, M et al. World J Urol. 2003;20(6):392-9.
5. Madersbacher H, et al. Br J Urol. 1995;75(4):452-6.
6. Wiedemann A, et al. Euro J Ger. 2001;3(1):41-5.
7. Steward WF, et al. World J Urol. 2002;20(6):327-36.
8. Herbison P, et al. BMJ. 2003;326:841.
9. Hay-Smith J, et al. Cochrane Database Syst Rev. 2003;(3):CD003781.
10. Van Kerrebroeck P, et al. Urology. 2001;57)3):414-21.
11. Anderson RU, et al. J Urol. 1999;161(6):1809-12.
12. Sussman D, Garely A. Curr Urol Res Opin. 2002;18(4):177-84.
13. Dmochowski R, et al. J Urol. 2002;168:580-6.