Patient compliance benefits from once-daily timolol solution

Philadelphia-The recently approved topical formulation of timolol maleate ophthalmic solution 0.5% (Istalol, Ista Pharmaceuticals) is a noteworthy addition to glaucoma specialists' armamentarium. The ocular penetration of the medication has increased as a result of the addition of potassium sorbate. The increased penetration, in turn, allows for once-daily dosing, a real boon for patient compliance.

Potassium sorbate was shown in animal studies to increase the ocular penetration of timolol maleate. L. Jay Katz, MD, explained that with the addition of potassium sorbate, the drug molecule and the salt become increasingly lipophilic. This action allowed the medication to pass through the outer cornea layer and penetrate the subsequent layers more easily compared with other formulations of timolol, he said.

"A group of Japanese researchers-Masayo Higashiyama and colleagues from Senju Pharmaceuticals Co., Japan-showed that by changing the molecule to one that is more lipophilic, ocular penetration in animals was easier and there were higher concentrations of the drug in the aqueous. The thought was that if this result is true, then perhaps once-a-day dosing could be realized in the clinical setting," Dr. Katz said.

Dr. Katz, who is co-director, Glaucoma Service, Wills Eye Hospital, and professor of ophthalmology, Jefferson Medical College, both in Philadelphia, uses Istalol because of the once-daily dosing. Other once-daily formulations include timolol gel-forming solution (Timoptic XE, Merck) and the generic timolol maleate (Alcon Laboratories)-which are associated with blurred vision upon instillation, according to Dr. Katz.

"If a patient has an objection to blurred vision in the morning, which can happen with a gel-forming solution, Istalol is a nice alternative," he said.

The advantage of prescribing a beta-blocker for use in the morning, he explained, is that the peak effect of the drug occurs within a couple of hours after instillation at the time of day when the IOP is the highest and production of aqueous is at its greatest.

Dr. Katz said that the efficacy of timolol maleate seems to be comparable with other formulations of timolol that were used previously.

The topical solution has the same side effects that are associated with other beta-blocking agents (i.e., asthma in predisposed patients and bradycardia). With Istalol there may be stinging upon instillation in the eye. It is interesting to note that timolol with potassium sorbate has less effect on the heart rate than that caused by timolol maleate solution given twice daily, he said.

"Likely, there is less effect on the heart rate because of once-daily dosing. Also, there may be less systemic absorption due to the increased ocular penetration," Dr. Katz said.

"Istalol may be a bit safer to use, but the potential side effects of a beta-blocker should not be ignored," he added.

The stinging sensation upon instillation is more intense than that experienced with other formulations of timolol but does not seem to dissuade patients from continuing with the drug, according to Dr. Katz.

"Istalol is a nice alternative therapy to the timolol formulations that were available previously," Dr. Katz said.