Objectives: To provide an overview on the efficacy, tolerability, safety and health-related quality of life (HRQoL) of drugs with a mixed action used in the treatment of overactive bladder (OAB). Evidence Acquisition: MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words ‘overactive bladder’, ‘detrusor overactivity’, ‘oxybutynin’, ‘propiverine’, and ‘flavoxate’. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis. Evidence Synthesis: Old and conflicting data do not support the use of flavoxate, while both propiverine and oxybutynin were found to be more effective than placebo in the treatment of OAB. Propiverine was at least as effective as oxybutynin but with a better tolerability profile even in the pediatric setting. Overall, no serious adverse event for any product was statistically significant compared to placebo. Improvements were seen in HRQoL with treatment by the oxybutynin transdermal delivery system and propiverine extended release. Conclusions: While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices.

1.
Abrams P, Cardozo L, Fall M, et al: The standardisation of terminology of lower urinary tract function: report for the Standardisation Sub-committee of the International Continence Society. Neurourol Urodynam 2002;21:167–178.
2.
McKillop C: Interview with Chris Chapple overactive bladder: tackling the problem. Eur Urol 2006;49:921–923.
3.
Chapple CR, Artibani W, Cardozo LD, et al: The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects. BJU Int 2005;95:335–340.
4.
Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ: How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001;87:760–766.
5.
Hu TW, Wagner TH, Bentkover JD, Leblanc K, Zhou SZ, Hunt T: Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology 2004;63:461–465.
6.
Wein AJ, Rovner ES: The overactive bladder: an overview for primary care health providers. Int J Fertil Womens Med 1999;44:56–66.
7.
Kobelt G, Kirchberger I, Malone-Lee J: Quality-of life aspects of the overactive bladder and the effect of treatment with tolterodine. BJU Int 1998;83:583–590.
8.
O’Conor R, Johannesson M, Hass S, Kobelt-Nguyen G: Urge incontinence: quality of life and patients’ valuation of symptom reduction. Pharmacoeconomics 1998;14:531–539.
9.
Liberman JN, Hunt TL, Stewart WF, et al: Health-related quality of life among adults with symptoms of overactive bladder: results from a US community-based survey. Urology 2001;57:1044–1050.
10.
US Census Bureau: Projections of the total resident population by 5-year age groups, and sex with special age categories. Population Projections Program, Population Division, US Census Bureau, 2000.
11.
Andersson KE, Chapple CR, Cardozo L, Cruz F, Hashim H, Michel MC, Tannenbaum C, Wein AJ: Pharmacological treatment of urinary incontinence. ICS guidelines 2009. 4th International Consultation on Incontinence. Curr Opin Urol 2009;19:380–394.
12.
Guarneri L, Robinson E, Testa R: A review of flavoxate: pharmacology and mechanism of action. Drugs Today 1994;30:91.
13.
Uckert S, Stief CG, Odenthal KP, et al: Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. Arzneimittelforschung 2000;50:456.
14.
Oka M, Kimura, Y, Itoh Y, et al: Brain pertussis toxin-sensitive G proteins are involved in the flavoxate hydrochloride-induced suppression of the micturition reflex in rats. Brain Res 1996;727:791.
15.
Caine M, Gin S, Pietra C, et al: Antispasmodic effects of flavoxate, MFCA, and REC 15/2053 on smooth muscle of human prostate and urinary bladder. Urology 1991;37:390.
16.
Milani R, Scalambrino S, Carrera S, Pezzoli P, Ruffmann R: Comparison of flavoxate hydrochloride in daily dosages of 600 versus 1,200 mg for the treatment of urgency and urge incontinence. J Int Med Res 1988;16:244–248.
17.
Herbst WP: Double-blind comparison of flavoxate and propantheline as urologic antispasmodics. Am J Clin Res 1970;1:65–67.
18.
Milani R, Scalambrino S, Milia R, et al: Double-blind crossover comparison of flavoxate and oxybutynin in women affected by urinary urge syndrome. Int Urogynecol J 1993;4:3.
19.
Wehnert J, Sage S: Comparative investigations to the action of Mictonorm (propiverine hydrochloride) and Spasuret (flavoxate hydrochloride) on detrusor vesicae. Z Urol Nephrol 1989;82:259.
20.
Fehrmann-Zumpe P, Karbe K, Blessman G: Using flavoxate as primary medication for patients suffering from urge symptomatology. Int Urogynecol J Pelvic Floor Dysfunct 1999;10:91–95.
21.
Gu FL, Reng ZY, Shang GZ, Shao HX, Wang B, Cheng ZD, Jiang Y, Zhao WP, Zheng JF, Qu CT, et al: Treatment of urgency and urge incontinence with flavoxate in the People’s Republic of China. J Int Med Res 1987;15:312–318.
22.
Briggs KS, Castleden CM, Asher MJ: The effect of flavoxate on uninhibited detrusor contractions and urinary incontinence in the elderly. J Urol 1980;123:665–666.
23.
Chapple CR, Parkhouse H, Gardener C, et al: Double-blind, placebo-controlled, cross-over study of flavoxate in the treatment of idiopathic detrusor instability. Br J Urol 1990;66:491–494.
24.
Dahm TL, Ostri P, Kristensen JK, et al: Flavoxate treatment of micturition disorders accompanying benign prostatic hypertrophy: a double-blind placebo-controlled multicenter investigation. Urol Int 1995;55:205–208.
25.
Roxburgh C, Cook J, Dublin N: Anticholinergic drugs versus other medications for overactive bladder syndrome in adults. Cochrane Database Syst Rev 2007;17: CD003190.
26.
Moon HS, Lee JW, Park SY, et al: Oxybutynin and propiverine suppress adenosine triphosphate-induced bladder overactivity other than through antimuscarinic mechanisms. Urology 2010;76:509.e8–e12.
27.
Van Meel TD, De Wachter S, Wyndaele JJ: The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity. Neurourol Urodyn 2010;29:391–394.
28.
McCrery RJ, Appell RA: Oxybutynin: an overview of the available formulations. Ther Clin Risk Manag 2006;2:19.
29.
Novara G, Galfano A, Secco S, et al: Systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol 2008;54:740–764.
30.
Chapple CR, Khullar V, Gabriel Z, et al: The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008;54:543–562.
31.
Nilsson CG, Lukkari E, Haarala M, Kivelä A, Hakonen T, Kiilholma P: Comparison of a 10-mg controlled release oxybutynin tablet with a 5-mg oxybutynin tablet in urge incontinent patients. Neurourol Urodyn 1997;16:533–542.
32.
Versi E, Appell R, Mobley D, Patton W, Saltzstein D, The Ditropan XL Study Group: Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. Obstet Gynecol 2000;95:718–721.
33.
Barkin J, Corcos J, Radomski S, et al: A randomized, double-blind, parallel-group comparison of controlled- and immediate-release oxybutynin chloride in urge urinary incontinence. Clin Ther 2004;26:1026–1036.
34.
Anderson RU, Mobley D, Blank B, Saltzstein D, Susset J, Brown JS, OROS Oxybutynin Study Group: Once-daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. Urology 1999;161:1809–1812.
35.
Birns J, Lukkari E, Malone-Lee JG: A randomized controlled trial comparing the efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin. BJU Int 2000;85:793–798.
36.
Corcos J, Casey R, Patrick A, et al: A double-blind randomized dose-response study comparing daily doses of 5 mg, 10 mg, and 15 mg controlled-release oxybutynin: balancing efficacy with severity of dry mouth. BJU Int 2006;97:520–527.
37.
Sussman D, Garely A: Treatment of overactive bladder with once-daily extended- release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET). Curr Med Res Opin 2002;18:177–184.
38.
Davila GW, Daugherty CA, Sanders SW, Transdermal Oxybutynin Study Group: A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001;166:140–145.
39.
Dmochowski RR, Sand PK, Zinner NR, Gittelman MC, Davila GW, Sanders SW, Transdermal Oxybutynin Study Group: Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology 2003;62:237–242.
40.
Van Kerrebroeck EV, Serment G, Dreher E: Clinical efficacy and safety of tolterodine compared to oxybutynin in patients with overactive bladder. Neurourol Urod 1997;16:478–479, abstr 91.
41.
Abrams P, Freeman R, Anderström C, Mattiasson A: Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998;81:801–810.
42.
Drutz HP, Appell RA, Gleason D, Klimberg I, Radomski S: Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 1999;10:283–289.
43.
Appell RA, Sand P, Dmochowski R, et al: Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study. Mayo Clin Proc 2001;76:358–363.
44.
Malone-Lee J, Shaffu B, Anand C, Powell C: Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial. J Urol 2001;165:1452–1456.
45.
Lee JG, Hong JY, Choo MS, et al: Tolterodina: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder. Int J Urol 2002;90:247–252.
46.
Diokno AC, Appell RA, Sand PK, et al: Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc 2003;78:687–695.
47.
Homma Y, Paick JS, Lee JG, Kawabe K, Japanese-Korean Tolterodine Study Group: Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial. BJU Int 2003;92:741–747.
48.
Giannitsas K, Perimenis P, Athanasopoulos A, Gyftopoulos K, Nikiforidis G, Barbalias G: Comparison of the efficacy of tolterodine and oxybutynin in different urodynamic severity grades of idiopathic detrusor overactivity. Eur Urol 2004;46:776–783.
49.
Homma Y, Kawabe K: Health-related quality of life of Japanese patients with overactive bladder treated with extended-release tolterodine or immediate-release oxybutynin: a randomized, placebo-controlled trial. World J Urol 2004;22:251–256.
50.
Leung HY, Yip SK, Cheon C, et al: A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder. BJU Int 2002;90:375–380.
51.
Altan-Yaycioglu R, Yaycioglu O, Aydin Akova Y, Guvel S, Ozkardes H: Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial. Br J Clin Pharmacol 2005;59:588–592.
52.
Halaska M, Ralph G, Wiedemann A, et al: Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;20:392–399.
53.
Zinner N, Tuttle J, Marks L: Efficacy and tolerability of darifenacin, a muscarinic M3-selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder. World J Urol 2005;23:248–252.
54.
Haruno A: Inhibitory effects of propiverine hydrochloride on the agonist-induced or spontaneous contractions of various isolated muscle preparations. Arzneimittelforschung 1992;42:815
55.
Tokuno H, Chowdhury JU, Tomita T: Inhibitory effects of propiverine on rat and guinea-pig urinary bladder muscle. Naunyn Schmiedebergs Arch Pharmacol 1993;348:659–662.
56.
Wuest M, Weiss A, Waelbroeck M, et al: Propiverine and metabolites: differences in binding to muscarinic receptors and in functional models of detrusor contraction. Naunyn Schmiedebergs Arch Pharmacol 2006;374:387.
57.
Jünemann KP, Hessdörfer E, Unamba-Oparah I, Berse M, Brünjes R, Madersbacher H, Gramatté T: Propiverine hydrochloride immediate and extended release: comparison of efficacy and tolerability in patients with overactive bladder. Urol Int 2006;77:334–339.
58.
Franco I: Pediatric overactive bladder syndrome: pathophysiology and management. Paediatr Drugs 2007;9:379–390.
59.
Nijman RJ, Bower W, Ellsworth P, Butler U, Tekgul S, Von Gontard A: Diagnosis and management of urinary incontinence and encopresis in childhood; in Abrams P, Cardozo L, Khoury S, Wein A (eds): Incontinence, ed 3. Plymouth/UK, Health Publications, 2005, pp 965–1058.
60.
Marschall-Kehrel D, Feustel C, Persson de Geeter C, Stehr M, Radmayr C, Sillén U, Strugala G:Treatment with propiverine in children suffering from nonneurogenic overactive bladder and urinary incontinence: results of a randomized placebo-controlled phase 3 clinical trial. Eur Urol 2009;55:729–736.
61.
Allousi S, Mürtz G, Braun R, et al: Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with idiopathic detrusor overactivity – a multicenter observational cohort study. ICS Annual Meeting, Montreal 2005, abstr 269.
62.
Nentwich HJ: Therapy of enuresis with a paediatric tablet of propiverine (Mictonetten) (in German). Kinderaerztl Prax 1986;54:329–333.
63.
Otto-Unger G: Treatment of the unstable bladder in children with the anticholinergic agent propiverine hydrochloride (Mictonorm/Mictonetten) (in German). Z Urol Nephrol 1985;78:145–152.
64.
Batinic D, Muertz G, Schnabel F, Gramattè T, Kirch W: Efficacy and tolerability of propiverine in children suffering from overactive bladder – a double-blind, randomised, clinical trial versus oxybutynin and placebo. Eur Urol Suppl 2002;1:113.
65.
Alloussi S, Mürtz G, Braun R, Gerhardt U, Heinrich M, Hellmis E, Horn W, Marschall-Kehrel D, Niklas K, Raabe M, Rössler T, Seibt B, Siemer S, Schultz-Lampel D, Walter H, Wiedeking B, Alloussi S, Bock P, Strugala G, Madersbacher H: Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with urge incontinence due to overactive bladder: results of a multicentre observational cohort study. BJU Int 2010;106:550–556.
66.
Madersbacher H, Mürtz G, Alloussi S, Domurath B, Henne T, Körner I, Niedeggen A, Nounla J, Pannek J, Schulte-Baukloh H, Schultz-Lampel D, Bock P, Strugala G: Propiverine vs. oxybutynin for treating neurogenic detrusor overactivity in children and adolescents: results of a multicentre observational cohort study. BJU Int 2009;103:776–781.
67.
Grigoleit U, Mürtz G, Laschke S, Schuldt M, Goepel M, Kramer G, Stöhrer M: Efficacy, tolerability and safety of propiverine hydrochloride in children and adolescents with congenital or traumatic neurogenic detrusor overactivity – a retrospective study. Eur Urol 2006;49:1114–1121.
68.
Schulte-Baukloh H, Mürtz G, Henne T, Michael T, Miller K, Knispel HH: Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis. BJU Int 2006;97:355–358.
69.
Dorschner W, Stolzenburg JU, Griebenow R, Halaska M, Schubert G, Mürtz G, Frank M, Wieners F: Efficacy and cardiac safety of propiverine in elderly patients – a double-blind, placebo-controlled clinical study. Eur Urol 2000;37:702–708.
70.
Lee KS, Lee HW, Choo MS, Paick JS, Lee JG, Seo JT, Lee JZ, Lee YS, Yoon H, Park CH, Na YG, Jeong YB, Lee JB, Park WH: Urinary urgency outcomes after propiverine treatment for an overactive bladder: the ‘propiverine study on overactive bladder including urgency data’. BJU Int 2010;105:1565–1570.
71.
Choo MS, Song C, Kim JH, Choi JB, Lee JY, Chung BS, Lee KS: Changes in overactive bladder symptoms after discontinuation of successful 3-month treatment with an antimuscarinic agent: a prospective trial. J Urol 2005;174:201–204.
72.
Jünemann KP, Halaska M, Rittstein T, Mürtz G, Schnabel F, Brünjes R, Nurkiewicz W: Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder. Eur Urol 2005;48:478–482.
73.
Abrams P, Cardozo L, Chapple C, Serdarevic D, Hargreaves K, Khullar V; 1032 Study Group: Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome. Int J Urol 2006;13:692–698.
74.
Madersbacher H, Halaska M, Voigt R, Alloussi S, Höfner K: A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int 1999;84:646–651.
75.
Stöhrer M, Mürtz G, Kramer G, Schnabel F, Arnold EP, Wyndaele JJ, Propiverine Investigator Group: Propiverine compared to oxybutynin in neurogenic detrusor overactivity – results of a randomized, double-blind, multicenter clinical study. Eur Urol 2007;51:235–242.
76.
Yamaguchi O, Marui E, Kakizaki H, Itoh N, Yokota T, Okada H, Ishizuka O, Ozono S, Gotoh M, Sugiyama T, Seki N, Yoshida M, Japanese Solifenacin Study Group: Randomized, double-blind, placebo- and propiverine-controlled trial of the once-daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder. BJU Int 2007;100:579–587.
77.
Christ T, Wettwer E, Wuest M, Braeter M, Donath F, Champeroux P, Richard S, Ravens U: Electrophysiological profile of propiverine – relationship to cardiac risk. Naunyn Schmiedebergs Arch Pharmacol 2008;376:431–440.
78.
Pakulski C, Drobnik L, Millo B: Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier. Med Sci Monit 2000;6:314–318.
79.
Ouslander JG: Management of overactive bladder. N Engl J Med 2004;350:786–799.
80.
Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D’Angelo K: Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc 1998;46:8–13.
81.
Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K: Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006;332:455–459.
82.
Oki T, Kageyama A, Takagi Y, Uchida S, Yamada S: Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder. J Urol 2007;177:766–770.
83.
Todorova A, Vonderheid-Guth B, Dimpfel W: Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol 2001;41:636–644.
84.
Pietzko A, Dimpfel W, Schwantes U, Topfmeier P: Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. Eur J Clin Pharmacol 1994;47:337–343.
85.
Flynn DD, Reever CM, Ferrari-DiLeo G: Pharmacological strategies to selectivity label and localize muscarinic receptor subtypes. Drug Dev Rev 1997;40:104–116.
86.
Oki T, Takagi Y, Inagaki S, Taketo MM, Manabe T, Matsui M, Yamada S: Quantitative analysis of binding parameters of [3H]N-methylscopolamine in central nervous system of muscarinic acetylcholine receptor knockout mice. Brain Res Mol Brain Res 2005;133:6–111.
87.
Kay GG, Granville LJ: Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly. Clin Ther 2005;27:127–138.
88.
Maruyama S, Oki T, Otsuka A, Shinbo H, Ozono S, Kageyama S, Mikami Y, Araki I, Takeda M, Masuyama K, et al: Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder. J Urol 2006;175:365–369.
89.
Ohtake A, Saitoh C, Yuyama H, Ukai M, Okutsu H, Noguchi Y, Hatanaka T, Suzuki M, Sato S, Sasamata M, et al: Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. Biol Pharm Bull 2007;30:54–58.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.