When fixed-combination is viable option

September 1, 2013

A new fixed-combination of brinzolamide-brimonidine is a safe and effective option for lowering IOP in patients who are not candidates for a beta-blocker.

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A new fixed-combination of brinzolamide-brimonidine is a safe and effective option for lowering IOP in patients who are not candidates for a beta-blocker.

Dr. Whitson

 

Dallas-The new fixed-combination of brinzolamide 1% plus brimonidine 0.2% (Simbrinza Suspension, Alcon Laboratories) is a safe and effective option for lowering IOP in patients with glaucoma or ocular hypertension uncontrolled on monotherapy.

The medication also brings the benefits of fixed-combination therapy to individuals who have contraindications to a beta-blocker, said Jess T. Whitson, MD.

Dr. Whitson is professor of ophthalmology, University of Texas Southwestern Medical Center, Dallas, and the lead author of a recently published paper (Clin Ophthalmol. 2013;7:1053-1060) reporting the 6-month results from one of the two pivotal clinical trials that led to FDA approval of brinzolamide-brimonidine.

The randomized study began with a 3-month double-masked phase comparing three times daily treatment with brinzolamide-brimonidine against the carbonic anhydrase inhibitor (brinzolamide) or alpha-agonist (brimonidine) alone. After 3 months, mean IOP at all measured time points (8 a.m., 10 a.m., 3 p.m., and 5 p.m.) was significantly lower in patients using the fixed-combination than in the monotherapy groups.

The study was continued for a 3-month safety extension, and at 6 months, mean IOP was stable in all treatment groups and no new or increased safety signals emerged. After 6 months in the fixed-combination group, percent IOP reduction from baseline ranged from 20% at trough to 30.7% at peak.

“There is a large pool of potential candidates for a fixed-combination IOP-lowering agent,” Dr. Whitson said. “Recent studies and national drug plan prescription data show that as many as 40% of patients with glaucoma are [taking] more than one medication to control IOP.”

Why fixed-combination may be best option

There are many reasons to choose a fixed-combination for these individuals.

Patient compliance may be enhanced because of the simplicity of instilling one drop instead of two and by the lower cost of having just one co-payment.

“In addition, a fixed-combination avoids the potential for drop washout if patients do not wait a sufficient time between instilling their medications, and its use lessens ocular surface exposure to preservatives like benzalkonium chloride,” Dr. Whitson said.

However, there has been a need for a beta-blocker-free fixed-combination since cardiac and pulmonary conditions-which are contraindications to an ophthalmic beta-blocker-are prevalent in the elderly population of patients being treated for ocular hypertension and glaucoma.

The new combination of brinzolamide plus brimonidine meets this need, Dr. Whitson noted.

Pivotal trial

The pivotal trial randomly assigned 690 patients with ocular hypertension or open-angle glaucoma. Eligible participants underwent a washout period ranging from 5 to 28 days, depending on what medication(s) they were using, and patients had to have IOP at two consecutive visits ranging from 24 to 36 mm Hg at 8 a.m. and from 21 to 36 mm Hg at 10 a.m.

Patients were instructed to administer their medication at 8 a.m., 3 p.m., and 10 p.m., and returned for follow-up visits after 2 weeks, 6 weeks, 3 months, and 6 months.

Data on adverse events and from pulse rate and blood pressure monitoring demonstrated that the fixed-combination had good systemic safety. Local ocular adverse events accounted for the majority of adverse event reports in all groups, and the types of adverse events reported were those expected based on experience with brinzolamide and brimonidine.

Use of brinzolamide alone or in combination was associated with all cases of blurred vision and nearly all reports of dysgeusia, while use of brimonidine alone or in combination was associated with all or nearly all cases of conjunctivitis, dry mouth, and ocular allergy.

“This 6-month study has a relatively short duration, and some cases of allergy or other adverse events may only develop over longer term use,” Dr. Whitson said.

Seventy-two of 77 patients who discontinued study participation because of an adverse event were using brimonidine either alone (34 patients) or as the fixed-combination (38 patients). There were no serious treatment-related adverse events in any study group.

Jess T. Whitson, MD

E: jess.whitson@utsouthwestern.edu

Dr. Whitson is on the speaker’s bureau for Alcon Laboratories, Allergan, Merck, and Sucampo.

 

 

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