The evolving pharmacotherapeutic profile of brimonidine, an alpha 2-adrenergic agonist, after four years of continuous use.

Since its introduction in 1996, use of brimonidine tartrate 0.2% ophthalmic solution (Alphagan, Allergan), a highly selective alpha 2-adrenergic agonist, has become increasingly popular for the initial and long-term management of ocular hypertension and glaucoma. Recently, ongoing clinical comparison trials of up to three years in length have reported sustained intraocular pressure (IOP) lowering efficacy with brimonidine 0.2% b.i.d., which was comparable with timolol 0.5% (Timoptic; Merck & Co.), accompanied by a favourable tolerability and safety profile. Also, many post-market studies have demonstrated the utility of brimonidine 0.2% b.i.d. as mono- and adjunctive therapy. Furthermore, major inroads have been made in the study of other possible pharmacotherapeutic benefits of brimonidine treatment, namely the potential for neuroprotection. This review will present a brief developmental history and examine key pharmacotherapeutic characteristics of brimonidine, including its receptor selectivity, IOP-lowering mechanism of action and potential neuroprotective activities. Moreover, the literature on brimonidine's efficacy and safety profiles in the treatment of ocular hypertension and glaucoma will be perused, and new four-year data from an ongoing double-masked clinical study comparing brimonidine tartrate 0.2% with timolol 0.5%, b.i.d. will be introduced. Brimonidine 0.2% b.i.d. provided sustained IOP-lowering efficacy comparable to timolol 0.5% b.i.d., with no significant differences at trough or peak during year four of continuous use. Visual fields were well preserved in both treatment groups with 93% of brimonidine patients and 91% of timolol patients showing no change or improvement. Brimonidine continued to appear safe and well-tolerated, with no clinically significant effects on mean heart rate or blood pressure, and no serious drug-related adverse events (AEs). Two out of 36 brimonidine patients developed ocular allergy; both were resolved without sequelae. Overall post-market surveillance found no reports of unexpected or serious drug-related AEs. These long-term results, in conjunction with those reported in the literature, suggest that brimonidine 0.2% b.i.d. is a highly appropriate first- and second-line therapy for long-term management of glaucoma and ocular hypertension. Potential neuroprotective effects of brimonidine therapy, which might provide additional vision sparing benefit, although supported by compelling animal studies, await clinical verification.