Combined glaucoma drugs offer clinical advantages

When medically indicated, combination products have advantages greater than the sum of their parts.

DALLAS — Treatment with combination glaucoma products can be more efficacious than concomitant administration of their component drugs, according to a study presented here.

Combination drugs lead to better control of intraocular pressure (IOP) through increased drug efficiency and improved compliance, said Joel S. Schuman, MD, here at the annual meeting of the American Academy of Ophthalmology. They can also reduce toxicity from vehicle or preservatives and can reduce cost.

Dr. Schuman said existing combination products, and others to be introduced shortly, can offer clear advantages when a single therapy is inadequate. Such combinations include Cosopt (dorzolamide HCl, timolol maleate ophthalmic solution, Merck), which is currently available to physicians and Xalcom (latanoprost, timolol maleate, Pharmacia Corp.), which is awaiting FDA approval.

“Combination therapies should only be used when single therapy is ineffective,” he said. “This minimizes side effects, toxicity and cost.”

Efficiency, compliance

Dr. Schuman said combination products can increase the efficiency of drug delivery. He said there is an immediate loss of drug upon instillation because the tear volume in the cul de sac is roughly 7 µL and the typical drop size equals approximately 30 µL to 50 µL. This excess immediately leaves the eye through normal drainage channels, including uptake into the nasolacrimal system. An additional 2 µL leaves the eye with each blink.

“An instilled eye drop disappears from the cul de sac within approximately 5 minutes,” Dr. Schuman said. “If the second eye drop were to be instilled prior to the complete disappearance of the first, that is, 5 minutes, the first medication is washed out by the second, reducing the efficiency of the first eye drop.”

“Compliance can be enhanced by reducing the number of medications and the frequency of medical administration,” Dr. Schuman said. Multiple medications, multiple dosing requirements, side effects, inadequate counseling and patients’ misconceptions about their disease can all cause suboptimal compliance. Studies have shown, he said, that “the more a therapeutic regimen interferes with or alters a patient’s daily pattern of living, the less likely it is to be followed.”

Effect on IOP

Dr. Schuman said some studies show better IOP reduction with Cosopt than with separate administration of its component drugs. In a study by Choudhri and colleagues, the authors evaluated 75 patients using a beta blocker plus dorzolamide in both eyes. Sixty of the patients were using a non-selective beta blocker and 15 were using a selective one. The eye with the higher IOP was switched to Cosopt. The fellow control eye continued with both separate drops.

Pressure decreases of 2.5 mm Hg in the non-selective beta blocker group and 2.2 mm Hg in the selective group were attained. There was no significant change in the control eyes.

“These results may be due to increased compliance and a reduction in the washout effect,” Dr. Schuman said.

Other studies, however, have demonstrated the effect of Cosopt to be similar to administration of its component drugs, he noted. “Large multicenter clinical studies show Cosopt performed similarly to concomitant therapy with its components at peak and slightly worse at trough.”

Noting that the large multicenter studies “used typical study patients and … were performed as strict clinical studies as opposed to the Choudhri study, which was performed in real world conditions,” Dr. Schuman posited that patients in the more formal studies may have been more diligent in waiting 5 minutes between instillation and thus may have attained better results.

Another study by Diestelhorst and colleagues found IOPs as much as 4 mm Hg lower in eyes treated with Xalcom versus treatment with its component drugs singly. “The pressure difference was significant between the combinations and the components,” Dr. Schuman noted.

Other advantages

Reduction of ocular exposure to preservative agents by 50% as well as reduced exposure to potential container contamination are other advantages to be considered, Dr. Schuman said. In addition, there may be a reduced drug cost, with combinations being less expensive than if the drugs were purchased separately.

“The daily cost of the component drugs is greater than the same amount of the fixed combination product, Cosopt,” he said. “This is true even considering the use of generic timolol plus dorzolamide in most instances, even if dorzolamide is dosed three times a day instead of twice a day.”

For Your Information:

• Joel S. Schuman, MD, can be reached at the New England Eye Center, 750 Washington St., Boston MA 02111: (617) 636-7950; fax: (617) 636-4866; e-mail: jss@mediaone.net. Dr. Schuman has no direct financial interest in any of the products mentioned, nor is he a paid consultant for any companies.

References:

• Choudhri S, Wand M, Shields MB. Comparison of dorzolamide-timolol fixed combination therapy to concomitant administration of a topical beta-blocker and dorzolamide. Am J Ophthalmol. 2000; 130: 832.
• Diestelhorst M, Almegard B. Comparison of two fixed combinations of latanoprost and timolol in open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 1998;236(8):577-581.