June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Severe CNS-related adverse events in patients receiving fixed-combination brinzolamide 1%/brimonidine 0.2% ophthalmic solution
Author Affiliations & Notes
  • Stephen C. Gieser
    Wheaton Eye Clinic, Wheaton, IL
  • Footnotes
    Commercial Relationships Stephen Gieser, Alcon (F), Allergan (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5692. doi:
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      Stephen C. Gieser; Severe CNS-related adverse events in patients receiving fixed-combination brinzolamide 1%/brimonidine 0.2% ophthalmic solution. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5692.

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      © ARVO (1962-2015); The Authors (2016-present)

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Topical ocular alpha-agonists used in the treatment of glaucoma have been associated with low rates of fatigue and hypotension in clinical trials. Severe CNS-related events observed in clinical practice have not been adequately characterized. This retrospective review of patient records was conducted to assess the occurence of central nervous system (CNS)-related adverse events reported by patients receiving fixed-combination brinzolamide 1%/brimonidine 0.2% ophthalmic solution (Simbrinza®, Alcon) in clinical practice and to characterize the reporting population.


Medical records of patients in my practice who received fixed-combination brinzolamide/brimonidine ophthalmic drops for the treatment of glaucoma between May 2013 and April 2014 and reported CNS-related adverse events including sedation, falls, and hypotension were reviewed. Patient demographics, administration regimens, and signs and symptoms were recorded from the charts.


A cohort of six males and nine females, ages 44 to 88 years, was identified. Ten patients were dosed twice daily and five were dosed three times daily; all received treatment in both eyes. Nine patients reported severe, progressively incapacitating somnolence; six of these nine patients reported symptom onset less than one hour following eye drop administration. Four experienced falls (causing a subdural hematoma in one patient). Three had repeated blood pressure measurements less than 90/60 mmHg. All adverse events resolved completely upon discontinuation of fixed-combination brinzolamide/brimonidine ophthalmic drops.


The severity of CNS-related adverse events associated with the use of the combination of brinzolamide and brimonidine reported in clinical practice appears to exceed that reported in Phase III clinical trials. These events are likely related to a brimonidine overdose, and the rapid onset of symptoms may indicate a novel delivery through the blood brain barrier (BBB). Progressively worsening symptoms suggest drug accululation behind the BBB. Severe hypotension may worsen glaucomatous optic neuropathy. Sedation and falls increase the risk of grave injuries. These findings have adverse implications for public health and support a call for clinical vigilance and further research.


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