Timolol is well-tolerated for further pressure control in glaucoma

January 15, 2010

Timolol maleate 0.5%/sorbitol complex is a convenient, well-tolerated choice for adjunctive therapy in patients taking a prostaglandin analogue who need further IOP control.

San Francisco-Timolol maleate 0.5%/sorbitol complex (Istalol, ISTA Pharmaceuticals) is a convenient, effective, and well-tolerated choice for adjunctive therapy in patients taking a prostaglandin analogue who need further IOP control, according to the results of a clinical trial presented by Jason Bacharach, MD.

The investigator-masked study enrolled 40 patients who required additional IOP lowering after being treated with a stable regimen of latanoprost 0.005% (Xalatan, Pfizer) for at least 1 month. Patients were randomly assigned 1:1 to receive adjunctive treatment with timolol maleate/sorbitol complex once daily in the morning or brimonidine tartrate 0.1% (Alphagan P, Allergan) twice daily. IOP measurements were obtained at baseline and after 4 weeks at 8 a.m. (peak), 10 a.m., and 4 p.m. (trough). The study results were presented in a poster at the annual meeting of the American Academy of Ophthalmology.

The results showed both treatment groups achieved statistically significant reductions in IOP. However, timolol/sorbitol was associated with a greater and more consistent IOP-lowering effect throughout the day compared with brimonidine, said Dr. Bacharach, associate clinical professor of ophthalmology, California Pacific Medical Center, San Francisco, and medical director, North Bay Eye Associates, Sonoma County, CA.

"In theory, timolol is an excellent choice as an adjunct to latanoprost because it provides a complementary mechanism of action for reducing IOP, acting to suppress aqueous humor production; whereas the prostaglandin analogue acts primarily by increasing aqueous outflow," he said. "This unique formulation of timolol with sorbitol complex is the only aqueous-based timolol product approved by the FDA for once-daily dosing."

Dr. Bacharach said that the results of this study confirm that the timolol combination is highly effective as an adjunct to latanoprost, providing excellent, flat diurnal IOP curves. "They are also consistent with results of a large meta-analysis, conducted by van der Valk and colleagues, that found timolol provided potent and consistent IOP-lowering at peak and trough and was associated with greater IOP-lowering and less fluctuation compared with brimonidine," he added.

In the prospective study, mean baseline IOP values at the three measurement times ranged between 18.95 and 17.1 mm Hg in the timolol/sorbitol group and were consistently lower in the brimonidine group (range, 20.34 to 18.6 mm Hg). However, none of the between-group differences was statistically significant.

Measurements of IOP at 8 a.m., 10 a.m., and 4 p.m. at day 28 showed mean reductions from baseline ranged from 2.3 to 3.6 mm Hg in the timolol/sorbitol group and from 1 to 2.8 mm Hg in the brimondine group, although the greater IOP-lowering effect of timolol/sorbitol was not statistically significant. Mean IOP values at the three measurement times ranged from 15.38 to 14.78 mm Hg in the timolol/sorbitol group and from 18.13 to 17.61 mm Hg among brimonidine users, and the differences favoring the timolol/sorbitol group for having a lower mean IOP were statistically significant at both peak (p = 0.044) and trough (p = 0.010).

Novel formulation

The addition of the sorbitol complex in the proprietary formulation of timolol maleate enhances lipophilicty of the beta-blocker to increase its penetration through the cornea and into the anterior chamber. This improved ocular bioavailability favors 24-hour IOP control with once-daily dosing, but is not associated with increased systemic levels of timolol. Nevertheless, prescribers need to be aware that some systemic exposure can occur so that contraindications to topical beta-blockers still must be considered.

"In the absence of any [contraindications], the timolol/sorbitol product is a great choice whenever beta-blocker treatment is indicated," Dr. Bacharach said.