Brimonidine 0.15% effective adjunctive therapy for open-angle glaucoma, ocular hypertension

"Medications behave differently in an adjunct or add-on role than they do as primary therapy," said Robert J. Noecker, MD, vice chairman, University of Pittsburgh Medical Center (UPMC). "There's plenty of information for hypotensive agents used as monotherapy. In terms of combination therapies, there is good information available about how the older formulation of brimonidine 0.2% [Alphagan, Allergan] performs as an adjunct to latanoprost, but data are lacking regarding the newer purite-preserved formulations in this role."

Adjunctive agent

Patients included in the study had an IOP >18 mm Hg after 6 weeks or more of latanoprost monotherapy, and had no prior use of brimonidine 0.2% or brimonidine 0.15%. None had ocular surgery within the 3 months prior to study entry, nor functionally significant visual field loss or evidence of progressive visual field loss within the year.

"This was a typical clinical situation where after monotherapy, you'd like to see the IOP lowered a bit more," Dr. Noecker said. "At entry, the average baseline latanoprost-treated pressure was 21.9 mm Hg. After about a month, patients received additive therapy with brimonidine 0.15%."

Brimonidine 0.15% was administered twice daily, at 8 a.m. and 8 p.m. Measurements included IOP at peak drug effect (approximately 2 hours after the morning dose), and at trough drug effect (approximately 12 hours after the evening dose). Dr. Noecker and Earl found that the addition of brimonidine 0.15% to ongoing latanoprost therapy resulted in a significantly lower mean IOP at peak drug effect (p <0.001). At 1 month, the mean IOP lowered to 16.1 mm Hg; at 2 months, the mean IOP was at 16.8 mm Hg. From the latanoprost-treated baseline at peak drug effect, brimonidine 0.15% provided an additional mean IOP reduction of 5.8 mm Hg (26%) after 1 month (p <0.001), and an additional mean IOP reduction of 5.1 mm Hg (23%) at 2 months (p < 0.001).

Further, significant reductions in IOP were also observed at trough drug effect (p <0.002), with a mean IOP of 18.6 mm Hg at 1 month and 19.8 mm Hg at 2 months.

From the latanoprost-treated baseline at trough drug effect, additional mean IOP reductions of 3.3 mm Hg (15%) at 1 month (p <0.001) and 2 mm Hg (9%) at 2 months (p = 0.002) were observed.

The observed tolerability of brimonidine 0.15% was also favorable. No serious adverse effects were reported, with the most common side effects being ocular allergy (n = 2, 5%) and foreign body sensation (n = 2, 5%).

The researchers suggest that the demonstrated efficacy of brimonidine 0.15% as an adjunctive agent to latanoprost may be due to complementary mechanisms of action, with latanoprost and brimonidine both lowering IOP by increasing uveoscleral outflow and an additional action of brimonidine of decreasing aqueous production.