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 al pha(2)-adrenoceptor agonist, for treating chronically elevated intraoc ular pressure (IOP) and the prophylactic treatment of acute pressure r ises. In normal volunteers, brimonidine administered twice daily for f ive days at concentrations ranging from 0.08-0.5% lowered IOP 16-22% a nd was well-tolerated ocularly and systemically. In a 28-day study in 186 patients with glaucoma or ocular hypertension, maximum IOP lowerin g 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 blu rring, 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 preoperativel y postoperatively or both pre- and postoperatively significantly reduc ed the number of postoperative IOP spikes (1-2% of patients compared t o 23% receiving only vehicle). Systemic hypotension, dry mouth, lid re traction and conjunctival blanching occurred more frequently in patien ts who received the drug twice. Brimonidine 0.2% twice daily was compa red with three times daily in 101 patients. No significant differences were seen between the two regimens in mean change from baseline IOP w ith mean decreases ranging from 3.4 +/- 3.23 to 5.2 +/- 3.77 mm Hg (st andard 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 compla ints were blurring and oral dryness. Based upon results of these and o ther early studies, brimonidine 0.5% was selected for acute therapy fo r the prevention of postoperative intraocular pressure spikes and brim onidine 0.2% for chronic use in glaucoma and ocular hypertension.