Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies.

Clinical trials were conducted to evaluate brimonidine tartrate, an alpha 2-adrenoceptor agonist, for treating chronically elevated intraocular pressure (IOP) and the prophylactic treatment of acute pressure rises. In normal volunteers, brimonidine administered twice daily for five days at concentrations ranging from 0.08-0.5% lowered IOP 16-22% and was well-tolerated ocularly and systemically. In a 28-day study in 186 patients with glaucoma or ocular hypertension, maximum IOP lowering was 27.2% and 30.1% for brimonidine 0.2% and 0.5%, respectively. The most common adverse events were dry mouth fatigue/drowsiness, and blurring, which occurred significantly more frequently with brimonidine 0.5% than 0.2%. Brimonidine 0.5% was tested in 471 patients undergoing argon laser trabeculoplasty (ALT). One drop administered preoperatively, postoperatively or both pre- and postoperatively significantly reduced the number of postoperative IOP spikes (1-2% of patients compared to 23% receiving only vehicle). Systemic hypotension, dry mouth, lid retraction and conjunctival blanching occurred more frequently in patients who received the drug twice. Brimonidine 0.2% twice daily was compared with three times daily in 101 patients. No significant differences were seen between the two regimens in mean change from baseline IOP with mean decreases ranging from 3.4 +/- 3.23 to 5.2 +/- 3.77 mm Hg (standard deviation) with twice daily dosing, and from 2.8 +/- 3.26 to 4.9 +/- 3.70 mm Hg with three times daily dosing. The most common complaints were blurring and oral dryness. Based upon results of these and other early studies, brimonidine 0.5% was selected for acute therapy for the prevention of postoperative intraocular pressure spikes and brimonidine 0.2% for chronic use in glaucoma and ocular hypertension.