title: Impact of Combination Glaucoma Therapies on β-Blocker Exposure.
abstract: OBJECTIVE
  β-adrenergic receptor antagonists (β-blockers) used in the treatment of glaucoma are an often-overlooked source of systemic adverse events. Ophthalmic timolol has been associated with severe systemic adverse events including numerous cases resulting in death. In recent years the number of fixed-dose combination therapies for glaucoma has grown rapidly, and among available combination therapies only the nonselective β-blocker timolol is used as the β-blocker component.
  
  
  METHODS
  A population-based study was conducted in Ontario, Canada between January 1, 2001 and December 31, 2012 to assess the shift to combination therapies in the management of glaucoma, and to investigate the impact of this shift on the relative use of selective and nonselective β-blockers in patients with this disease.
  
  
  RESULTS
  Between 2001 and 2012 timolol (nonselective β-blocker) use grew at an average annual rate of 2.2% (P<0.0001), whereas betaxolol (selective β-blocker) use declined by 14.1% per year (P<0.0001). These changes in the relative use of betaxolol and timolol coincided with changes in the relative use of combination and single-drug therapies. Over the study period, the use of β-blockers as single-drug therapy decreased by 7.7% annually (P<0.0001). In contrast, the use of combination therapies containing a β-blocker increased by 7.6% annually (P<0.0001).
  
  
  CONCLUSIONS
  The introduction of fixed combination glaucoma therapies has been associated with a significant shift to greater use of nonselective β-blockers. In vulnerable older populations, this may have an important impact on patient safety that warrants further study.
authors.affiliation: *Department of Ophthalmology §Division of Geriatric Medicine, Queen's University †Department of Ophthalmology, Hotel Dieu and Kingston General Hospitals ‡Institute for Clinical Evaluative Sciences-Queen's University Site ∥Division of Geriatric Medicine, St. Mary's of the Lake Hospital, Kingston, Canada.
authors.forename: Kunyong
authors.initials: K
authors.lastname: Xu
authors.forename: Erica de L P
authors.initials: EL
authors.lastname: Campbell
authors.forename: Sudeep S
authors.initials: SS
authors.lastname: Gill
authors.forename: Robert
authors.initials: R
authors.lastname: Nesdole
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Campbell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D015784:Betaxolol / Q000627:therapeutic use*; D004338:Drug Combinations; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization / Q000706:statistics & numerical data*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D013999:Timolol / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D013999:Timolol; D015784:Betaxolol