title: 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.
authors.affiliation: a University of Alberta , Edmonton , Canada ;
authors.forename: Adrian
authors.initials: A
authors.lastname: Wagg
authors.affiliation: b New York University , USA ;
authors.forename: Victor W
authors.initials: VW
authors.lastname: Nitti
authors.affiliation: c Guy's and St Thomas' NHS Foundation Trust , UK ;
authors.forename: Con
authors.initials: C
authors.lastname: Kelleher
authors.affiliation: d University Hospital of the Canary Islands , Spain ;
authors.forename: David
authors.initials: D
authors.lastname: Castro-Diaz
authors.affiliation: e Astellas Pharma Europe Ltd , Chertsey , Surrey , UK ;
authors.forename: Emad
authors.initials: E
authors.lastname: Siddiqui
authors.affiliation: f Formerly of Astellas Scientific and Medical Affairs , Northbrook , IL , USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Berner
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects; D001794:Blood Pressure; D002986:Clinical Trials as Topic; D003248:Constipation / Q000139:chemically induced; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects*; D011446:Prospective Studies; D012189:Retrospective Studies; D000069464:Solifenacin Succinate / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage*; D000068737:Tolterodine Tartrate / Q000009:adverse effects; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D000083:Acetanilides; D000319:Adrenergic beta-Antagonists; D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; D013844:Thiazoles; D000068737:Tolterodine Tartrate; C526675:fesoterodine; D000069464:Solifenacin Succinate; C520025:mirabegron
keywords: Antimuscarinic; Older; Overactive bladder; Tolerability; β3-adrenoceptors