FDA approval of brimonidine/timolol fixed combination may boost adherence

November 15, 2007

The FDA has approved the fixed combination of brimonidine tartrate 0.2%/timolol maleate 0.5% (Combigan, Allergan). The product is considered a useful new option for add-on or replacement therapy in patients requiring additional IOP lowering.

Key Points

Oct. 31, Allergan announced that it had received approval from the FDA to market its fixed combination of brimonidine tartrate 0.2%/timolol maleate 0.5% (Combigan).

The ophthalmic solution is indicated for the reduction of elevated IOP in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP. The ophthalmic solution is recommended to be administered twice daily, approximately every 12 hours, and will be available next month.

Clinical trial results

The fixed combination of brimonidine/timolol was investigated in five key studies. The pivotal trials comprised two identically designed, 12-month, double-masked studies that randomly assigned patients 1:1:1 to treatment with brimonidine/timolol twice daily, brimonidine three times daily, or timolol twice a day. A total of 1,159 patients were enrolled, and IOP was measured at 8 a.m., 10 a.m., 3 p.m., and 5 p.m. during follow-up visits at weeks 2 and 6 and months 3, 6, 9, and 12.

Results showed the fixed combination was associated with mean IOP reductions from baseline ranging from 4.4 to 7.6 mm Hg (up to 33%) across all visits. Compared with timolol b.i.d., the fixed combination of brimonidine/timolol provided an additional 1 to 2 mm Hg decrease in IOP. The difference between treatments was statistically significant for all measurement times at all visits. Relative to brimonidine t.i.d., fixed-combination treatment afforded a 1 to 3 mm Hg additional decrease in IOP that achieved statistical significance at 8 a.m., 10 a.m., and 3 p.m. at all visits.

"The 5 p.m. measurement was obtained just 2 hours after the most recent dose of brimonidine but 9 hours after the morning dose of the fixed combination," Dr. Craven said.

"[Brimonidine/timolol] was first approved in Canada and has been available there for about 4 years," he continued. "In a Canadian post-marketing study, Andy Crichton, MD, [Calgary, Alberta] reported [that the ophthalmic solution] was a great adjunct or replacement therapy. For the average patient, its efficacy was essentially equivalent to that achieved with concomitant administration of brimonidine and timolol."