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). Study design and methods: Meta-analysis of safety and tolerability results from two previously reported prospective, randomized, 12-month, double-masked, multi-center, 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). Main outcome measure: 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 <= 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 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.