Efficacy, once-daily convenience make drug good choice

January 15, 2006

Portland, OR—The novel formulation of timolol maleate 0.5% ophthalmic solution containing potassium sorbate (Istalol, ISTA Pharmaceuticals) is a good option to consider for adjunctive therapy in patients whose IOP is not adequately controlled by a prostaglandin analogue alone, said John R. Samples, MD.

Portland, OR-The novel formulation of timolol maleate 0.5% ophthalmic solution containing potassium sorbate (Istalol, ISTA Pharmaceuticals) is a good option to consider for adjunctive therapy in patients whose IOP is not adequately controlled by a prostaglandin analogue alone, said John R. Samples, MD.

"Compared with other medication choices, timolol provides a greater and more consistent IOP-lowering effect throughout the daytime, and this proprietary preparation of timolol offers the only ophthalmic timolol solution that is approved by the FDA for once-daily administration," said Dr. Samples, professor of ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland.

"Based on the work of Brubaker and others, it is well established that beta-blockers don't work well to lower IOP as well at night; however, they are very effective when used first thing in the morning to blunt the usual pressure rise that many patients experience around the time of awakening," he said. "Therefore, this once-daily timolol product combined with a once-nightly prostaglandin analogue allows patients who need dual therapy a simple and convenient dosing regimen."

Dr. Samples noted his opinion that most ophthalmologists probably consider timolol as their first choice for adjunctive therapy with a prostaglandin analogue. However, the results of a recently published meta-analysis provide solid evidence to support that role [van der Valk et al. Ophthalmology 2005;112:1177-1185].

Published in a leading peer-reviewed ophthalmology journal, the independent study was conducted by researchers from the department of epidemiology, Maastricht University, The Netherlands, with no industry sponsorship. It pooled data on the IOP-lowering effects of medications evaluated in randomized clinical trials published through 2003.

To be considered for inclusion, papers had to be written in English, German, French, or Dutch, and 85% or more of the study population had to consist of patients with primary open-angle glaucoma or ocular hypertension. Data from evaluations performed after 1 month of treatment were available from 28 studies that included trough effect data for 6,953 participants and peak measurement data for 6,841 individuals.

The non-prostaglandin medications tested were betaxolol, timolol, dorzolamide, brinzolamide, and brimonidine. For both peak and trough measurements, timolol was associated with the greatest mean percent IOP reduction from baseline (–27% and –26%, respectively). Brimonidine had the second greatest IOP-lowering effect at peak (–25%), but was much less efficacious at trough (–18%).

Data from placebo-treated patients showed IOP was lowered by an average of 5% at both peak and trough in the control groups. Effects of the three prostaglandin analogues-latanoprost, travoprost, and bimatoprost-ranged from 31% to 33% at peak and from 28% to 29% at trough. Based on the data, the investigators concluded that the prostaglandin analogues and timolol are the most effective IOP-reducing agents in patients with primary open-angle glaucoma or ocular hypertension.

Dr. Samples noted the novel, once-daily timolol maleate solution may be preferred by some patients over gel-forming preparations that can cause transient blurriness of vision, and while it affords better anterior chamber penetration of timolol than competitor solutions, its use is not associated with an increase in systemic levels of the beta-blocker.

A randomized, double-masked, crossover study investigated that issue in healthy subjects who used the timolol maleate-potassium sorbate solution or a standard timolol solution twice daily for 8 days. In blood samples drawn prior to the morning dose on the eighth day, the mean timolol concentration was significantly lower when patients used the timolol maleate-potassium sorbate preparation compared with the standard formulation, 0.09 versus 0.2 ng/ml, respectively. Six subjects had detectable levels of timolol after using the sorbate-containing solution compared with seven subjects using the standard timolol solution, and the maximum concentration achieved in any one subject was also lower after continued dosing with the novel formulation compared with the standard, 0.28 versus 0.69 ng/ml, respectively.