Abstract
A randomized, double-blind, placebo-controlled, four-way crossover, safety study of darifenacin versus oxybutynin was carried out on 76 patients with overactive bladder (OAB). Adults with OAB received 2 weeks each of darifenacin 15 and 30 mg once daily (q.d.), oxybutynin 5 mg three times daily (t.i.d.) and placebo, in random sequence at 10-day intervals. Darifenacin and oxybutynin significantly reduced incontinence episodes, and the number/severity of urgency episodes (all P<0.05 versus placebo). Improvements in OAB symptoms with darifenacin were dose-dependent. Dry mouth was less common with darifenacin 15 mg than oxybutynin (13% and 36%; P<0.05), while constipation was comparable (10% and 8%, respectively). Corresponding rates for darifenacin 30 mg were 34% and 21%, respectively. Patients only reported blurred vision or dizziness with oxybutynin (3% and 2%, respectively). Darifenacin (15 mg q.d.) provides comparable efficacy with improved tolerability versus oxybutynin (5 mg t.i.d.) in the treatment of patients with OAB.
Similar content being viewed by others
References
Abrams P, Kelleher CJ, Kerr LA, Rogers RG (2000) Overactive bladder significantly affects quality of life. Am J Manag Care 6 [Suppl 11]: S580
Anderson KE (1993) Pharmacology of lower urinary tract smooth muscles and penile and erectile tissues. Pharmacol Rev 45: 253
Andersson K-E (2002) Potential benefits of muscarinic M3 receptor selectivity. Eur Urol Suppl 1: 23
Cardozo L, Prescott K, Serdarevic D, Skillern L (2003) Can medication prolong warning time?. Neurourol Urodyn 22: A74
Chess-Williams R, Chapple CR, Yamanishi T, Yasuda K, Sellers DJ (2001) The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro. J Auton Pharmacol 21: 243
Donnellan CA, Fook L, McDonald P, Playfer JR (1997) Oxybutynin and cognitive dysfunction. BMJ 315: 1363
Fetscher C, Fleichman M, Schmidt M, Krege S, Michel MC (2002) M3 muscarinic receptors mediate contraction of human urinary bladder. Br J Pharmacol 136: 641
Haab F, Stewart L, Dwyer P (2004) Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol 45: 420
Hegde SS, Choppin A, Bonhaus D, Briaud S, Loeb M, Moy TM, Loury D, Eglen RM (1997) Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol 120: 1409
Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D’Angelo K (1998) Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc 46:8
Kay G (2004) The M3 selective receptor antagonist darifenacin has no clinically relevant effect on cognition and cardiac function. Prog Urol 14 [Suppl 3]: 22
Kelleher CJ, Cardozo LD, Khullar V, Salvatore S (1997) A medium-term analysis of the subjective efficacy of treatment for women with detrusor instability and low bladder compliance. Br J Obstet Gynaecol 104: 988
Lawrence M, Guay DR, Benson SR, Anderson MJ (2000) Immediate-release oxybutynin versus tolterodine in detrusor overactivity: a population analysis. Pharmacotherapy 20: 470
Layton D, Pearce GL, Shakir SA (2001) Safety profile of tolterodine as used in general practice in England: results of prescription-event monitoring. Drug Saf 24: 703
Liberman JN, Hunt TL, Stewart WF, Wein A, Zhou Z, Herzog AR, Lipton RB, Diokno AC (2001) Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. Urology 57: 1044
Lipton RB, Kolodner K, Wesnes K (2005) Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol 173: 493
Mundy AR, Abrams P, Chapple CR, Neal DE (2001) Darifenacin, the first selective M3 antagonist for overactive bladder: comparison with oxybutynin on ambulatory urodynamic monitoring and salivary flow. Neurourol Urodyn 20: A221
Napier C, Gupta P (2002) Darifenacin is selective for the human recombinant M3 receptor subtype. Neurourol Urodyn 21: A445
Skerjanec A, Devineni D (2004) Affinity of darifenacin for the p-glycoprotein efflux pump: a mechanism contributing to the CNS sparing profile? British Pharmacological Society Winter meeting, 14–16 December, Newcastle, UK
Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ (2003) Prevalence and burden of overactive bladder in the United States. World J Urol 20: 327
Tsao JW, Heilman KM (2003) Transient memory impairment and hallucinations associated with tolterodine use. N Engl J Med 349: 2274
Wang P, Luthin GR, Ruggieri MR (1995) Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins. J Pharmacol Exp Ther 273: 959
Womack KB, Heilman KM (2003) Tolterodine and memory: dry but forgetful. Arch Neurol 60: 771
Wyndaele JJ (2001) The overactive bladder. BJU Int 88: 135
Yarker YE, Goa KL, Fitton A (1995) Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging 6: 243
Acknowledgements
We are grateful for the support of our co-investigators on this study: Robert Feldman, Dean Knoll, Jacques Susset, Glen Wells, Myron Murdock (all USA). This study was funded by Pfizer, Inc. Preparation of the manuscript was supported by an educational grant from Novartis Pharma AG, Basel, Switzerland. Editorial and project management services were provided by Thomson ACUMED.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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 23, 248–252 (2005). https://doi.org/10.1007/s00345-005-0507-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00345-005-0507-3