[RAMESH DORAIRAJAN]

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October 2017

Brimonidine – Alpha-Agonist Extraordinaire

Brimonidine, the alpha-agonist indicated for the reduction of intraocular pressure (IOP) and treatment of glaucoma, is a fairly indispensable agent representing the totality of one of five currently available classes of pressure lowering medications. Unlike other classes, where several molecules are available, brimonidine is the only molecule that may realistically be used to reduce IOP through the alpha-agonist pathway. Brimonidine is available in three different combinations (0.1%, 0.15% and 0.2%), with three different preservatives (purite, polyquad and BAK, respectively) and either as a solo agent or in a 0.2% combination with timolol 0.5% (Combigan; Allergan) or brinzolamide 1% (Simbrinza; Alcon). Depending on the concentration of brimonidine used, up to 20% of patients who are using brimonidine will eventually develop an allergy, which is a type IV hypersensitivity reaction characterized by follicular conjunctivitis, hyperemia and eyelid dermatitis.1 Detecting brimonidine allergy is a critical part of being an effective and compassionate glaucoma practitioner. But still, this unique allergy can throw you a few curveballs, so let’s look at a few key points for detecting and addressing brimonidine analogy: 1. The allergy can occur at any time. In addition, it is more likely to occur with higher concentrations of brimonidine, and less likely to occur with lower concentrations.2,3 It seems as if most reactions will occur within the first year.1 2. Timolol allergy is much rarer, but looks pretty much the same as brimonidine allergy. Therefore, I recommend that if a patient is on both medications, you assume it is the brimonidine (and discontinue it) and if that doesn’t work, come back later for the timolol. 3. A few things can mask brimonidine allergy. Steroids are the most common, and even a low dose steroid (e.g., loteprednol) can keep the allergy at bay. I don’t recommend this as a way of treating the allergy, because the patient will then have the steroid effect to contend with; it can confuse the diagnostician if a patient is on bilateral brimonidine and unilateral steroid, presenting with a unilateral conjunctivitis in the steroid naïve eye. 4. Timolol reduces the likelihood of brimonidine allergy.4,5 It is unclear why timolol would do this (believe me I have investigated), but several studies have shown the effect. Interestingly, timolol also appears to reduce hyperemia from prostaglandin analogs.6 5. Be proactive in at-risk patients. For any patient who is using brimonidine, ask yourself: “What if an allergy developed?” If the answer is that this would be horrible for the patient’s prognosis, consider proactively decreasing the risk of allergy by going to the lowest concentration of brimonidine, and reassess if a beta blocker could be a helpful part of the patient’s treatment.

Reference(s): 1. Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S; Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011 Apr;151(4):671-681. 2. Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma. 2002 Apr;11(2):119-126. 3. Cantor LB, Safyan E, Liu CC, Batoosingh AL. Brimonidine-purite 0.1% versus brimonidine-purite 0.15% twice daily in glaucoma or ocular hypertension: a 12-month randomized trial. Curr Med Res Opin. 2008 Jul;24(7):2035-2043. 4. Sherwood MB, Craven ER, Chou C, DuBiner HB, Batoosingh AL, Schiffman RM, Whitcup SM. Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial. Arch Ophthalmol. 2006 Sep;124(9):1230-1238. 5. Motolko MA. Comparison of allergy rates in glaucoma patients receiving brimonidine 0.2% monotherapy versus fixed-combination brimonidine 0.2%-timolol 0.5% therapy. Curr Med Res Opin. 2008 Sep;24(9):2663-2667. 6. Radcliffe NM. The impact of timolol maleate on the ocular tolerability of fixed-combination glaucoma therapies. Clin Ophthalmol. 2014 Dec 12;8:2541-2549.

Dr. Nathan M. Radcliffe is a clinical associate professor of ophthalmology at New York Eye and Ear Infirmary and is a cataract and glaucoma surgeon at the New York Eye Surgery Center.