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Combination anti-glaucoma drugs: win-win for patients and physicians


Medications used alone or in conjunction with prostaglandin have substantial IOP-lowering effects



Combination anti-glaucoma medications used alone or in conjunction with a prostaglandin have substantial IOP-lowering effects.


By Lynda Charters; Reviewed by Fiaz Zaman, MD


The availability of combination anti-glaucoma therapies is a boon for patients and physicians when considering that about 40% of patients with glaucoma require two or more drugs to control elevated IOP levels.

The advantages of combination products are obvious. For patients, fewer daily instillations of drops may be needed and the costs of the drugs then become lower because copays are eliminated. For physicians, the combination products increase patient compliance rates and the efficacy of the products reduces the IOP to more manageable levels.

In addition, while most patients are taking a prostaglandin drug with a normal dose of one drop once daily, most combination products require instillation of one drop twice daily, but washout is not an issue with the second or third prescribed drugs in contrast to when patients use multiple individual drugs, according to Fiaz Zaman, MD, in private practice at Houston Eye Associates, Houston.

Choosing the combination drug

Deciding which combination therapy to use for individual patients necessitates considering a number of factors.

There are three primary combination anti-glaucoma therapies, he pointed out:

·      Combigan (brimonidine tartrate/timolol maleate ophthalmic solution, Allergan),

·      Cosopt (dorzolamide hydrochloride-timolol maleate ophthalmic solution, Merck),

·      Simbrinza (brinzolamide/brimonidine tartrate ophthalmic suspension, Alcon).

Dr. Zaman prefers Combigan in his practice because multiple published studies have reported that the drug, when used with a prostaglandin, achieves a very significant decrease in IOP.

“Normally, when using adjunctive therapy, a minimal 15% to 20% IOP decrease is desired. Numerous studies have shown that Combigan prescribed in addition to a prostaglandin decreases IOP by 25% to 35%, which is phenomenal. The lower the IOP the better. In my opinion, there are sufficient data that indicate that the drug does a superb job,” he commented.

Cosopt also can lower IOP substantially. However, in a head-to-head study, Combigan had superior IOP-lowering ability. A disadvantage with Cosopt is that the generic formulations of the drug may not be as efficacious as the brand name formulation, which can be hard to find.

“I tend to avoid the generic drugs in glaucoma for that reason,” Dr. Zaman said.

Simbrinza, which is relatively new to the market, is advantageous for some patents because it does not contain a beta-blocker, he pointed out, in contrast to the other two combination drugs. “Simbrinza is a good medication choice for patients with asthma, for whom beta-blockers are contraindicated,” he said. A disadvantage of the Simbrinza is that it is FDA-approved only for instillation three times daily, which adds more to the treatment burden and patient compliance may become an issue. Another disadvantage is that the drug is in a suspension that requires shaking before instillation; failure to do so may result in less of the active ingredients being instilled in the eye.

A final consideration is allergic reactions to the glaucoma drugs. “With both Combigan and Simbrinza, the allergy rates are unknown. Brimonidine is a component of both drugs; when it was first introduced, it was associated with a 20% allergy rate. He said, “Once a patient has an allergic reaction to brimonidine, he or she is allergic for life, thus eliminating this class of medication from use.”

Combigan is associated with a low allergy rate (5%). The allergy rate for Simbrinza is unknown because it has been commercially available for only 6 months and its track record has yet to be determined.

Glaucoma management

The decisions for how patients with glaucoma are managed is based on three factor--the IOP, optic nerve structure, and visual function, according to Dr. Zaman.

“The only variable factor in the treatment of glaucoma that has been proven is that lowering the IOP prevents some optic nerve changes from occurring, which in turn decreases the risk of visual loss,” he said.

Monitoring of optic nerve changes is done by structural assessments using optic nerve photographs and optical coherence tomography, the Heidelberg Retina Tomograph (Heidelberg Engineering), and GDx-VCC scanning laser polarimetry (Zeiss Meditec) to evaluate the nerve fiber layer.

“Structural changes in the nerve fiber layer can indicate that glaucoma is progressing,” he explained.

Visual field testing is performed to examine the visual function to detect glaucomatous progression.

“In glaucoma, with progressive there is progressive loss of the peripheral visual fields that will ultimately enlarge to incorporate the central visual field, which can lead to blindness if untreated,” Dr. Zaman noted.

Therapy can be altered or other therapies added when progression of optic nerve damage and visual field loss becomes evident.

“Safety, efficacy, and compliance are all important when choosing an ocular medication. This is especially important because of the chronicity of glaucoma,” he said and explained that his drug choices are based on evidence-based medicine.

The future

Dr. Zaman is impressed with the currently available drugs for treating glaucoma. However, he looks to the future for improvements. “I think the future is bright for alternative therapies,” he said.


Fiaz Zaman, MD

E: fiazzaman@gmail.com

Dr. Zaman has no proprietary interest in any aspect of this report.



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