Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics

Abstract

Objective Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β₃-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.

Methods Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.

Results Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.

Conclusions Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.

Keywords:

• Antimuscarinic
• β3-adrenoceptors
• Older
• Overactive bladder
• Tolerability

Declaration of funding

Editorial assistance was funded by Astellas Pharma.

Declaration of financial/other relationships

A.W. has disclosed that he has received personal or institutional fees from Astellas, Pfizer and SCA for research, and for speaker and consultancy roles. V.W.N. has disclosed that he has participated in advisory boards for Allergan, Medtronic, Ipsen, Uroplasty and Astellas and has acted as an investigator for Allergan and Astellas. C.K. has disclosed that he has received consulting fees or honoraria and support for travel to meetings from Astellas and payment for lectures including service on speakers’ bureaus (honoraria and travel assistance) from Astellas, Allergan and Ethicon. D.C-D. has disclosed that he has received personal fees from Astellas, AMS, Allergan and Lilly for providing services as investigator, consultant and speaker. E.S. has disclosed that he is an employee of Astellas. T.B. has disclosed that he was formerly an employee of Astellas.

CMRO peer reviewer 1 has disclosed that he has received grants and is a consultant to Astellas, Pfizer, and Allergan; he is also a consultant to Ferring, and is on the speakers’ bureau of Astellas, Pfizer and Ferring. CMRO peer reviewer 2 has disclosed that she is a consultant to Allergan, Astellas, Pfizer and Ferring and is on the speakers’ bureau of Astellas, Allergan, Pfizer and Laborie. CMRO peer reviewers 3 and 4 have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Aideen Young PhD and Stuart Murray MSc of Envision Scientific Solutions for editorial assistance and Mary Beth Blauwet of Astellas Pharma Global Development for data checking.