Safety and tolerability of brimonidine purite 0.1% and brimonidine purite 0.15%: a meta-analysis of two phase 3 studies.
OBJECTIVE
To compare the safety and tolerability of two formulations of brimonidine ophthalmic solution, brimonidine Purite (P) 0.1% and brimonidine P 0.15%, for reducing intraocular pressure in patients with glaucoma or ocular hypertension (OHT).


METHODS
Meta-analysis of safety and tolerability results from two previously reported prospective, randomized, 12-month, double-masked, multicenter, parallel-group clinical studies with similar entry criteria and protocols. In study 1 (two clinical trials), after washout of previous medications, patients with glaucoma or OHT were randomized to thrice-daily treatment with brimonidine P 0.15% (n = 381), brimonidine P 0.2% (n = 383), or brimonidine 0.2% (n = 383). In study 2 (one clinical trial), the treatment arms were thrice-daily brimonidine P 0.1% (n = 215) and brimonidine 0.2% (n = 218).


METHODS
Treatment-related adverse events (AEs) and discontinuations due to AEs.


RESULTS
Treatment-related AEs were significantly reduced with brimonidine P 0.15% compared with brimonidine 0.2% in study 1 (p < 0.001). Treatment-related AEs and discontinuations due to AEs were significantly reduced with brimonidine P 0.1% compared with brimonidine 0.2% in study 2 (p < or = 0.014). In the meta-analysis of study 1 and study 2, the overall incidence of treatment-related AEs was lower with brimonidine P 0.1% than with brimonidine P 0.15% (41.4 vs. 49.7%; p = 0.050). Although the incidence of treatment-related ocular AEs was similar with brimonidine P 0.1% and 0.15% (p = 0.461), treatment-related systemic AEs were less frequent with brimonidine P 0.1% than with brimonidine P 0.15% (4.7 vs. 14.2%; p < 0.001), and there were fewer discontinuations due to systemic AEs with brimonidine P 0.1% than with brimonidine P 0.15% (p = 0.025).


CONCLUSIONS
Brimonidine P 0.1% has improved systemic safety and tolerability compared with brimonidine P 0.15%. The ocular safety and tolerability of the formulations are similar. The present meta-analysis is based on only two clinical studies, and additional studies further evaluating the safety and tolerability of these medications are warranted.
Cantor
Louis B
LB
Glaucoma Service, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, IN 46202, USA. lcantor@iupui.edu
Liu
Ching-Chi
CC
Batoosingh
Amy L
AL
Hollander
David A
DA
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D000068438:Brimonidine Tartrate; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions / Q000009:adverse effects; D009994:Osmolar Concentration; D011810:Quinoxalines / Q000008:administration & dosage* / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D028761:Withholding Treatment
D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D000068438:Brimonidine Tartrate