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Tolterodine in the Treatment of Male LUTS

  • Benign Prostatic Hyperplasia (K McVary, Section Editor)
  • Published:
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Abstract

Storage lower urinary tract symptoms (LUTS) in men are usually chronic, with a high prevalence and a substantial impact on quality of life; therefore, adequate therapies are desirable and crucial for these men. First line treatment for all patients with storage LUTS should always be behavioral. The gold standard for pharmacological treatment of overactive bladder/storage symptoms is a muscarinic receptor antagonist such as tolterodine. First-marketed antimuscarinics were limited by several adverse events such as dry mouth, constipation, tachycardia, accommodation disorder, and cognitive dysfunction, resulting in poor compliance and early treatment discontinuation in a large number of patients. In order to improve compliance with oral drug treatment, tolterodine was developed, providing a better efficacy/adverse event profile. Tolterodine is available in the following two formulations: the intermediate release (IR) and extended release form (ER). Tolterodine ER 4 mg administered once daily is pharmacokinetically equivalent to tolterodine IR 2 mg twice daily but has a lower incidence of adverse events and increased efficacy. Combination therapy of tolterodine and an alpha-blocker is significantly more efficacious than either monotherapy. Even when compared and added to tamsulosin, tolterodine shows a good safety profile. The incidence of acute urinary retention requiring catheterization and treatment withdrawals due to adverse events are low in all the studies included in the present review.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61:37–49.

    Article  PubMed  Google Scholar 

  2. McVary K. BPH: epidemiology and comorbidities. Am J Manag Care. 2006;12(5 Suppl):S122.

    PubMed  Google Scholar 

  3. Auffenberg GB, Helfand BT, McVary KT. Established medical therapy for benign prostatic hyperplasia. Urol Clin North Am. 2009;36(4):443–59.

    Article  PubMed  Google Scholar 

  4. Oelke M, Baard J, Wijkstra H, de la Rosette JJ, Jonas U, Höfner K. Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur Urol. 2008;54:419–26.

    Article  PubMed  Google Scholar 

  5. Haab F, Castro-Diaz D. Persistence with antimuscarinic therapy in patients with overactive bladder. Int J Clin Pract. 2005;59:931–7.

    Article  CAS  PubMed  Google Scholar 

  6. Gormley EA, Lightner DJ, Burgio KL, Chai TC, Clemens JQ, Culkin DJ, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455–63.

    Article  PubMed  Google Scholar 

  7. Yarker YE, Goa KL, Fitton A. Oxybutynin: a review of its pharmacodynamics and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging. 1995;6:243–6.

    Article  CAS  PubMed  Google Scholar 

  8. Brynne N, Stahl MMS, Hallén BH, Edlund PO, Palmér L, Höglund P, et al. Pharmacokinetics and pharmacodynamics of tolterodine in man: a new drug for the treatment of urinary bladder overactivity. Int J Clin Pharmacol Ther. 1997;35:287–95.

    CAS  PubMed  Google Scholar 

  9. Stahl MMS, Ekström B, Sparf B, Mattiasson A, Andersson KE. Urodynamic and other effects of tolterodine: a novel antimuscarinic drug for the treatment of detrusor overactivity. Neurourol Urodyn. 1995;14:647–55.

    Article  CAS  PubMed  Google Scholar 

  10. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. Guidelines on the management of male Lower Urinary Tract Symptoms (LUTS) incl. Benign Prostatic Obstruction (BPO). Eur Urol. 2013;64:118–40. The EAU guidelines reported that short-term treatment with antimuscarinic drugs (tolterodine) in men with BOO appears safe, even if not all antimuscarinic agents have been tested in elderly men with LUTS and OAB symptoms.

  11. McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793–803. The AUA guideline comprehensively evaluated the published papers, concluding that anticholinergic agents are appropriate and effective treatment alternatives for the management of LUTS secondary to BPH in men without an elevated post void residual (PVR) urine and when LUTS are predominantly irritative.

  12. Chapple CR, Smith D. The pathophysiological changes in the bladder obstructed by benign prostatic hyperplasia. Br J Urol. 1994;73:117–23.

    Article  CAS  PubMed  Google Scholar 

  13. Kaplan SA, Walmsley K, Te AE. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol. 2005;174:2273–6.

    Article  PubMed  Google Scholar 

  14. Kaplan SA, Roehrborn CG, Dmochowski R, Rovner ES, Wang JT, Guan Z. Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia. Urology. 2006;68:328–32.

    Article  PubMed  Google Scholar 

  15. Abrams P, Kaplan SA, De Koning Gans HJ, Millard R. Safety and tolerability of tolterodine for the treatment of overactive bladder in Men with bladder outlet obstruction. J Urol. 2006;175(3 Pt 1):999–1004.

    Article  CAS  PubMed  Google Scholar 

  16. Roehrborn CG, Abrams P, Rovner ES, Kaplan SA, Herschorn S, Guan Z. Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence. BJU Int. 2006;97:1003–6.

    Article  CAS  PubMed  Google Scholar 

  17. Athanasopoulos A, Gyftopoulos K, Giannitsas K, et al. Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study. J Urol. 2003;169:2253–6.

    Article  CAS  PubMed  Google Scholar 

  18. Lee JY, Kim HW, Lee SJ, et al. Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int. 2004;94:817–20.

    Article  CAS  PubMed  Google Scholar 

  19. Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006;296:2319–28.

    Article  CAS  PubMed  Google Scholar 

  20. Chapple C, Herschorn S, Abrams P, Sun F, Brodsky M, Guan Z. Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers. Eur Urol. 2009;56(3):534–41.

    Article  CAS  PubMed  Google Scholar 

  21. Postlind H, Danielson A, Lindgren A, Andersson SH. Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes P450 2D6 and 3A in human liver microsomes. Drug Metab Dispos. 1998;26(4):289–93.

    CAS  PubMed  Google Scholar 

  22. Larsson G, Hallén B, Nilvebrant L. Tolterodine in the treatment of overactive bladder: analysis of the pooled phase II efficacy and safety data. Urology. 1999;53(5):990–8.

    Article  CAS  PubMed  Google Scholar 

  23. Nilvebrant L, Andersson KE, Gillberg PG, Stahl M, Sparf B. Tolterodine: a new bladder-selective antimuscarinic agent. Eur J Pharmacol. 1997;327(2–3):195–207.

    Article  CAS  PubMed  Google Scholar 

  24. Olsson B, Szamosi J. Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation vs. immediate release tolterodine clinical pharmacokinetics. Clin Pharmacokinet. 2001;40(3):227–35.

    Article  CAS  PubMed  Google Scholar 

  25. Clemett D, Jarvis B. Tolterodine. Drugs Aging. 2001;18(4):277–304.

    Article  CAS  PubMed  Google Scholar 

  26. Malone-Lee JG, Walsh JB, Maugourd MF. Tolterodine: a safe and effective treatment for older patients with overactive bladder. J Am Geriatr Soc. 2001;49(6):700–5.

    Article  CAS  PubMed  Google Scholar 

  27. Chung DE, Te AE. Tolterodine extended-release for overactive bladder. Expert Opin Pharmacother. 2009;10(13):2181–94.

    Article  CAS  PubMed  Google Scholar 

  28. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A, Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology. 2001;57(3):414–21.

    Article  PubMed  Google Scholar 

  29. Novara G, Galfano A, Secco S, D’Elia C, Cavalleri S, Ficarra V, et al. A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol. 2008;54:740–63.

    Article  CAS  PubMed  Google Scholar 

  30. Yang Y, Zhao XF, Li HZ, Wang W, Zhang Y, Xiao H, et al. Efficacy and safety of combined therapy with terazosin and tolterodine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study. Chin Med J (Engl). 2007;120:370–4.

    CAS  Google Scholar 

  31. Chapple CR, Herschorn S, Abrams P, et al. Efficacy and safety of tolterodine extended-release in men with overactive bladder symptoms treated with an alpha-blocker: effect of baseline prostatespecific antigen concentration. BJU Int. 2010;106:1332–8.

    Article  CAS  PubMed  Google Scholar 

  32. Höfner K, Burkart M, Jacob G, Jonas U. Safety and efficacy of tolterodine extended release in men with overactive bladder symptoms and presumed nonobstructive benign prostatic hyperplasia. World J Urol. 2007;25:627–33.

    Article  PubMed  Google Scholar 

  33. Chung DE, Te AE, Staskin DR, Kaplan SA. Efficacy and safety of tolterodine extended release and dutasteride in male overactive bladder patients with prostates >30 grams. Urology. 2010;75(5):1144–8.

    Article  PubMed  Google Scholar 

  34. Chapple CR, Martinez-Garcia R, Selvaggi L, et al. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Eur Urol. 2005;48:464–70.

    Article  CAS  PubMed  Google Scholar 

  35. Wagg A, Compion G, Fahey A, Siddiqui E. Persistence with prescribed antimuscarinic therapy for overactive bladder: a UK experience. BJU Int. 2012;110(11):1767–74.

    Article  CAS  PubMed  Google Scholar 

  36. Chapple C, Herschorn S, Abrams P, et al. Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with a-blockers. Eur Urol. 2009;56:534–43.

    Article  CAS  PubMed  Google Scholar 

  37. Athanasopoulos A, Chapple C, Fowler C, Gratzke C, Kaplan SA, Stief C, et al. The role of antimuscarinics in the management of men with symptoms of overactive bladder associated with concomitant bladder outlet obstruction: an update. Eur Urol. 2011;60(1):94–105. The good review of Athanasopoulos et al. focused on the contemporary role of antimuscarinics in the management of men with symptoms of bladder outlet obstruction and concomitant overactive bladder. They confirmed the safety of antimuscarinics for these patients and concluded that the addition of an antimuscarinic seems to offer an amelioration of the symptoms and a moderate improvement in quality of life.

    Article  CAS  PubMed  Google Scholar 

  38. 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;78:687–95.

    Article  CAS  PubMed  Google Scholar 

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Compliance with Ethics Guidelines

Conflict of Interest

Mauro Gacci has received support for travel to meetings for the study, manuscript preparation or other purposes, and payment for lectures from GSK, Eli-Lilly, Menarini, Pfizer, and Bayer.

Giacomo Novara has been an advisory board member or speaker for Astellas, GlaxoSmithKleine, Lilly, Menarini, Nycomed, Pfizer Inc., Pierre Fabre, and Recordati.

Matthias Oelke has worked on the advisory board for Eli-Lilly and Company and has received payment for lectures from Eli-Lilly and Company, Pfizer and Bayer.

Stavros Gravas has been advisory board member or speaker for Astellas, GlaxoSmithKleine, Pierre Fabre, and Angelini Pharma Hellas.

Arcangelo Sebastianelli, Matteo Salvi, Riccardo Schiavina, Eugenio Brunocilla, Cosimo De Nunzio, Andrea Tubaro, Marco Carini, Sergio Serni each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Urology, University of Florence, Careggi Hospital, Florence, Italy

    Mauro Gacci, Arcangelo Sebastianelli, Matteo Salvi, Marco Carini & Sergio Serni

  2. Department of Urology, University of Bologna, Bologna, Italy

    Riccardo Schiavina & Eugenio Brunocilla

  3. Department of Surgical, Oncological and Gastroenterological Sciences, Urology Clinic, University of Padua, Padova, Italy

    Giacomo Novara

  4. Department of Urology, Sant’Andrea Hospital, University ‘La Sapienza’, Rome, Italy

    Cosimo De Nunzio & Andrea Tubaro

  5. Department of Urology, Hannover Medical School, Hannover, Germany

    Matthias Oelke

  6. Department of Urology, University Hospital of Larissa, Larissa, Greece

    Stavros Gravas

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  1. Mauro Gacci
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Correspondence to Mauro Gacci.

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This article is part of the Topical Collection on Benign Prostatic Hyperplasia

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Gacci, M., Sebastianelli, A., Salvi, M. et al. Tolterodine in the Treatment of Male LUTS. Curr Urol Rep 16, 60 (2015). https://doi.org/10.1007/s11934-015-0531-9

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  • DOI: https://doi.org/10.1007/s11934-015-0531-9

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