I.V. Kuzmin1, S.V. Kuzmina1,2
1I.P. Pavlov First St. Petersburg State Medical University, Saint-Petersburg, Russian Federation
2Toksovskaya Interdistrict Hospital, Toksovo village, Russian Federation
The review presents data on the epidemiology, clinical course and modern methods to the treatment of overactive bladder. It also describes the pharmacological bases of anticholinergic drug use, which are first-line in the treatment of this disease. The pharmacological and clinical aspects of the new M-holinoblocker, fesoterodine, are considered. The drug belongs to the competitive blockers of M2-and M3-cholinergic receptors. The conducted studies have shown the high clinical efficacy of fesoterodine. Due to the low lipophilicity and large molecular weight, the drug’s ability to penetrate the blood-brain barrier is minimal, which causes a low frequency of adverse events from the central nervous system. The pharmacokinetic and pharmacodynamic properties of fesoterodine allow it to be prescribed to "vulnerable" groups of patients — the elderly, patients with CNS diseases and cognitive disorders. According to the FORTA system, fesoterodine is the only antimuscarinic drug classified in category B. The results of a multiple-criteria decision-making showed a favorable benefit-risk profile of fesoterodine, prescribed according to a flexible dosage regimen of 4 mg and 8 mg. Important benefits of fesoterodine are the convenience of intake, the possibility of dose titration, as well as the ratio of treatment costs and its efficacy. The practical issues of using fesoterodine in various clinical cases are considered.
Keywords: overactive bladder, anticholinergic therapy, fesoterodine, multiple-criteria decision-making, FORTA classification.
For citation: Kuzmin I.V., Kuzmina S.V. Anticholinergic therapy of an overactive bladder: clinical practice aspects. Russian Medical Inquiry. 2021;5(5):273–279 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-273-279.
Acknowledgment
The authors and Editorial Board are grateful to Pierre Fabre for providing full-text foreign articles required to write the review.
About the authors:
Igor V. Kuzmin — Dr. Sc. (Med.), Professor of the Department of Urology, I.P. Pavlov First St. Petersburg State Medical University; 6–8, Lev Tolstoy str., St. Petersburg, 197022, Russian Federation; ORCID iD 0000-0002-7724-7832.
Svetlana V. Kuzmina — C. Sc. (Med.), Assistant Professor of Department of Neurology, I.P. Pavlov First St. Petersburg State Medical University; 6–8, Lev Tolstoy str., St. Petersburg, 197022, Russian Federation; Head of the Department of Neurology, Toksovskaya Interdistrict Hospital; 18, Bulanov str., Toksovo village, 188664, Leningrad region, Russian Federation; ORCID iD 0000-0002-8602-7268.
Contact information: Igor V. Kuzmin, e-mail: kuzminigor@mail.ru.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 15.07.2021.
Revised 05.08.2021.
Accepted 30.08.2021.
2. Abrams P., Chapple C.R., Jünemann K.P., Sharpe S. Urinary urgency: a review of its assessment as the key symptom of the overactive bladder syndrome. World J Urol. 2012;30(3):385–392. DOI: 10.1007/s00345-011-0742-8.
3. Irwin D.E., Milsom I., Hunskaar S. et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50(6):1306–1314. DOI: 10.1016/j.eururo.2006.09.019.
4. Кузьмин И.В. Эпидемиологические аспекты гиперактивного мочевого пузыря и ургентного недержания мочи. Урологические ведомости. 2015;5(3):30–34. DOI: 10.17816/uroved5330-34. [Kuzmin I.V. Epidemiological aspects of overactive bladder and urge urinary incontinence. Urology reports (St.-Petersburg). 2015;5(3):30–34 (in Russ.)]. DOI: 10.17816/uroved5330-34.
5. Milsom I., Irwin D.E. A cross‐sectional, population‐based, multinational study of the prevalence of overactive bladder and lower urinary tract symptoms: results from the EPIC study. Eur Urol Suppl. 2007;6(1):4–9.
6. Кузьмин И.В. Патогенез, клиническое течение и лечение гиперактивности мочевого пузыря: Дис. … д-ра мед. наук. СПб.; 2007. [Kuzmin I.V. Pathogenesis, clinical course and treatment of overactive bladder: thesis. SPb.; 2007 (in Russ.)].
7. Аль-Шукри С.Х., Кузьмин И.В. Качество жизни больных с гиперактивностью мочевого пузыря. Урологические ведомости. 2011;1(1):21–26. [Al-Shukri S.Kh., Kuzmin I.V. Quality of life in patients with overactive bladder. Urology reports (St.-Petersburg). 2011;1(1):21–26 (in Russ.)].
8. Кульчавеня Е.В., Холтобин Д.П. Гиперактивный мочевой пузырь у сложного пациента: какой препарат выбрать? Урология. 2021;(1):120–125. DOI: 10.18565/urology.2021.1.120-125. [Kulchavenya E.V., Kholtobin D.P. Overactive bladder in a complicated patient: which drug to choose? Urologiia. 2021;(1):120–125 (Russ.)]. DOI: 10.18565/urology.2021.1.120-125.
9. Shafik A., Shafik I.A. Overactive bladder inhibition in response to pelvic floor muscle exercises. World J Urol. 2003;20(6):374–377. DOI: 10.1007/s00345-002-0309-9.
10. Rai B.P., Cody J.D., Alhasso A., Stewart L. Anticholinergic drugs versus non-drug active therapies for non-neurogenic overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2012;12(12):CD003193. DOI: 10.1002/14651858.CD003193.pub4.
11. Кузьмин И.В., Аюб А.Х., Слесаревская М.Н. Ингибиторы фосфодиэстеразы 5-го типа в лечении дисфункций нижних мочевых путей. Урологические ведомости. 2020;10(1):67–74. DOI: 10.17816/uroved10167-74. [Kuzmin I.V., Ajub A.Kh., Slesarevskaya M.N. Phosphodiesterase type 5 inhibitors in treatment of lower urinary tract dysfunctions. Urology reports (St. Petersburg). 2020;10(1):67–74 (in Russ.)]. DOI: 10.17816/uroved10167-74.
12. Abrams P., Andersson K.E. Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007;100(5):987–1006. DOI: 10.1111/j.1464-410X.2007.07205.x.
13. Аль-Шукри С.Х., Кузьмин И.В., Амдий Р.Э. Комплексное лечение больных с нестабильностью детрузора. Урология. 2001;(5):26–29. [Al-Shukri S.Kh., Kuzmin I.V., Amdiy R.E. Complex treatment of patients with detrusor instability. Urologiia. 2001;(5):26–29 (in Russ.)].
14. Аляев Ю.Г., Гаджиева З.К. М-холиноблокаторы в лечении гиперактивного мочевого пузыря. Эффективная фармакотерапия. 2010;(29):28–35. [Alyaev Yu.G., Gadzhieva Z.K. M-anticholinergics in the treatment of overactive bladder. Effective pharmacotherapy. 2010;(29):28–35 (in Russ.)].
15. Hegde S.S. Muscarinic receptors in the bladder: from basic research to therapeutics. Br J Pharmacol. 2006;147(Suppl 2):S80–87. DOI: 10.1038/sj.bjp.0706560.
16. Ehlert F.J., Ahn S., Pak K.J. et al. Neuronally released acetylcholine acts on the M2 muscarinic receptor to oppose the relaxant effect of isoproterenol on cholinergic contractions in mouse urinary bladder. J Pharmacol Exp Ther. 2007;322(2):631–637. DOI: 10.1124/jpet.107.121756.
17. Pontari M.A., Braverman A.S., Ruggieri M.R. Sr. The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. Am J Physiol Regul Integr Comp Physiol. 2004;286(5):R874–880. DOI: 10.1152/ajpregu.00391.2003.
18. Daly D.M., Chess-Williams R., Chapple C., Grundy D. The inhibitory role of acetylcholine and muscarinic receptors in bladder afferent activity. Eur Urol. 2010;58(1):22–28. DOI: 10.1016/j.eururo.2009.12.030.
19. Matsumoto Y., Miyazato M., Furuta A. et al. Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats. Urology. 2010;75(4):862–867. DOI: 10.1016/j.urology.2009.12.013.
20. Meeting highlights from the Committee for Medicinal Products for Human Use, 19–22 February 2007 (Electronic resource.) URL: https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use19–22-february-2007 (access date: 06.16.2021).
21. US Food and Drug Administration. (Electronic resource.) URL: https://www.accessdata.fda.gov/ (access date: 06.16.2021).
22. Инструкция по медицинскому применению препарата Товиаз® (Электронный ресурс.) URL: https://grls.rosminzdrav.ru/ (дата обращения: 16.08.2021). [Instructions for the medical use of the drug Toviaz® (Electronic resource.) URL: https://grls.rosminzdrav.ru/ (access date: 08.16.2021) (in Russ.)].
23. Gupta K., Kaur K., Aulakh B.S., Kaushal S. Fesoterodine for overactive bladder: A review of the literature. Curr Ther Clin Exp. 2010;71(5):273–288. DOI: 10.1016/j.curtheres.2010.10.003.
24. Кузьмин И.В., Аль-Шукри С.Х. Фезотеродин в лечении гиперактивного мочевого пузыря: фармакологические основы и клинические результаты. Урологические ведомости. 2020;10(2):163–171. DOI: 10.17816/uroved102163-171. [Kuzmin I.V., Al-Shukri S.K. Fesoterodine for the treatment of overactive bladder: pharmacological bases and clinical results. Urology reports (St.-Petersburg). 2020;10(2):163–171 (in Russ.)]. DOI: 10.17816/uroved102163-171.
25. Simon H.U., Malhotra B. The pharmacokinetic profile of fesoterodine: similarities and differences to tolterodine. Swiss Med Wkly. 2009;139(9–10):146–151. DOI: smw-12542.
26. Chapple C., Matthias O., Kaplan S.A. et al. Fesoterodine clinical efficacy and safety for the treatment of overactive bladder in relation to patient profiles: a systematic review. Curr Med Res Opin. 2015;31(6):1201–1243.
27. Malhotra B., Gandelman K., Sachse R., Wood N. Assessment of the effects of renal impairment on the pharmacokinetic profile of fesoterodine J Clin Pharmacol. 2009;49(4):477–482. DOI: 10.1177/0091270009332434.
28. Chapple C., Van Kerrebroeck P., Tubaro A. et al. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Eur Urol. 2007;52(4):1204–1212. DOI: 10.1016/j.eururo.2007.07.009.
29. Cardozo L., Khullar V., El-Tahtawy A. et al. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder. BMC Urol. 2010;10:14. DOI: 10.1186/1471-2490-10-14.
30. Morris V., Wagg A. Does fesoterodine have a role in the treatment of poorly managed patients with overactive bladder? Drug Des Devel Ther. 2014;8:113–119. DOI: 10.2147/DDDT.S40032.
31. Malhotra B.K., Wood N., Sachse R. Influence of age, gender, and race on pharmacokinetics, pharmacodynamics, and safety of fesoterodine. Int J Clin Pharmacol Ther. 2009;47(9):570–578.
32. Van Kerrebroeck P.E., Heesakkers J., Berriman S. et al. Long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder symptoms. Int J Clin Pract. 2010;64(5):584–593. DOI: 10.1111/j.1742-1241.2010.02361.x.
33. Nitti V.W., Rovner E.S., Bavendam T. Response to fesoterodine in patients with an overactive bladder and urgency urinary incontinence is independent of the urodynamic finding of detrusor overactivity. BJU Int. 2010;105(9):1268–1275. DOI: 10.1111/j.1464-410X.2009.09037.x.
34. Yonguc T., Sefik E., Inci I. et al. Randomized, controlled trial of fesoterodine fumarate for overactive bladder in Parkinson’s disease. World J Urol. 2019. DOI: 10.1007/s00345-019-02981-7.
35. Yamada S., Ito Y., Nishijima S. et al. Basic and clinical aspects of antimuscarinic agents used to treat overactive bladder. Pharmacol Ther. 2018;189:130–148. DOI: 10.1016/j.pharmthera.2018.04.010.
36. Kerdraon J., Robain G., Jeandel C. et al. Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly. Prog Urol. 2014;24(11):672–681. DOI: 10.1016/j.purol.2014.06.003.
37. Callegari E., Malhotra B., Bungay P.J. et al. A comprehensive non‐clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. Br J Clin Pharmacol. 2011;72(2):235–246.
38. Wagg A.S., Herschorn S., Carlsson M. et al. What are the chances of improvement or cure from overactive bladder? A pooled responder analysis of efficacy and treatment emergent adverse events following treatment with fesoterodine. Neurourol Urodyn. 2021;40(6):1559–1568. DOI: 10.1002/nau.24706.
39. Kay G.G., Maru P., Scholeld D. et al. Evaluation of cognitive function in healthy older subjects treated with fesoterodine. Postgrad Med. 2012;124(3):7–15. DOI: 10.3810/pgm.2012.05.2543.
40. Wagg A., Khullar V., Marschall‐Kehrel D. et al. Flexible‐dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double‐blind, placebo‐controlled study of fesoterodine in an aging population trial. J Am Geriatr Soc. 2013;61(2):185–193. DOI: 10.1111/jgs.12088.
41. DuBeau C.E., Kraus S.R., Griebling T.L. et al. Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double‐blind, placebo‐controlled trial. J Urol. 2014;191(2):395–404. DOI: 10.1016/j.juro.2013.08.027.
42. Harding K., Lapitan M.C., Arlandis S. et al. Non-neurogenic Female LUTS. EAU Guideline, 2021. (Electronic resource.) URL: https://uroweb.org/guideline/non-neurogenic-female-luts/#7 (access date: 06.16.2021).
43. Mattishent K., Bennett K., Campbell N.L. et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. DOI: 10.1136/bmj.k1315.
44. Oelke M., Becher K., Castro-Diaz D. et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014). Age Aging. 2015;44(5):745–755. DOI: 10.1093/ageing/afv077.
45. Wagg A., Oelke M., Angulo J.C. et al. Review of the efficacy and safety of fesoterodine for treating overactive bladder and urgency urinary incontinence in elderly patients. Drugs Aging. 2015;32(2):103–125. DOI: 10.1007/s40266-014-0237-6.
46. Kürzinger M.L., Douarin L., Uzun I. et al. Structured benefit-risk evaluation for medicinal products: review of quantitative benefit-risk assessment findings in the literature. Ther Adv Drug Saf. 2020;11:2042098620976951. DOI: 10.1177/2042098620976951.
47. Chapple C.R., Mironska E., Wagg A. et al. Multicriteria decision analysis applied to the clinical use of pharmacotherapy for overactive bladder symptom complex. Eur Urol Focus. 2020;6(3):522–530. DOI: 10.1016/j.euf.2019.09.020.
48. Milsom I., Wagg A., Oelke M., Chapple C. Which drugs are best for overactive bladder? From patients’ expectations to physicians’ decisions. Int J Clin Pract. 2021;75(4):e13870. DOI: 10.1111/ijcp.13870.
49. Heesakkers J., Espuña Pons M., Toozs Hobson P., Chartier-Kastler E. Dealing with complex overactive bladder syndrome patient profiles with focus on fesoterodine: in or out of the EAU guidelines? Res Rep Urol. 2017;9:209–218. DOI: 10.2147/RRU.S146746.
50. Филиппова О.В. Антимускариновые препараты в лечении гиперактивного мочевого пузыря: фармакотерапевтические свойства и фармакоэкономическая оценка. РМЖ. 2019;(2):42–46. [Filippova O.V. Antimuscarine drugs in the treatment of overactive bladder: pharmacotherapeutic properties and pharmacoeconomic evaluation. RMJ. 2019;2:42–48 (in Russ.)].
This work is licensed under a Creative Commons «Attribution» 4.0 License.
Распечатать