Latanoprost, timolol IOP control compared in crossover trial

Fort Lauderdale, FL-Latanoprost (Xalatan, Pfizer Ophthalmics) reduces IOP significantly more than does timolol gel-forming solution (GFS), results of a randomized, crossover clinical trial demonstrated.

Patients whose treatment was switched from timolol GFS to latanoprost had a further reduction in IOP, but no such reduction was observed when treatment was switched from latanoprost to timolol GFS, William C. Stewart, MD, told colleagues at the Association for Research in Vision and Ophthalmology (ARVO) meeting.

"The results seem to indicate that if you have a patient taking timolol and need a further reduction in IOP, switching to latanoprost might control the pressure, depending on how much further reduction is needed," said Dr. Stewart, clinical professor of ophthalmology at the University of South Carolina in Columbia and director of medical affairs for the Pharmaceutical Research Network in Charleston, SC. "On the other hand, if a patient is taking latanoprost and needs further IOP control, switching to timolol generally won't further reduce the pressure."

The evaluation of latanoprost and timolol GFS followed a previous comparison that involved morning dosing of timolol GFS. The current study compared latanoprost and evening dosing of timolol GFS.

"Our hypothesis was that latanoprost would reduce IOP more than timolol would," Dr. Stewart said. "This was a confirmatory study that was intended to prove or disprove whether latanoprost is better than timolol with evening dosing."

The study involved a total of 75 patients with primary open-angle glaucoma and ocular hypertension. The patients were randomly assigned to receive either once-daily 0.5% timolol GFS (n = 40) or once-daily 0.005% latanoprost (n = 35). After 8 weeks of treatment, patients crossed over to the other medication and were treated for an additional 8 weeks.

IOP was determined every 2 hours from 8 a.m. to 8 p.m. at baseline and weeks 8 and 16. Safety was assessed by visual acuity, slit lamp biomicroscopy, and adverse event reports.

During the first 8-week treatment period, latanoprost-treated patients had an average reduction in IOP of 6.9 mm Hg, which was significantly greater than the 5.5 mm Hg mean reduction among patients treated with timolol GFS (p = 0.034). Following crossover, patients switched from timolol GFS to latanoprost during the second 8-week period had a significant reduction in IOP compared with baseline (p < 0.001), but patients switched from latanoprost to timolol GFS did not have a significant reduction in IOP.

"I think the results are consistent with the literature," Dr. Stewart said. "If a patient is taking timolol and doesn't have adequate control, I think it would be best to add a second drug or to go to a fixed-dose combination."

Combining results from both treatment periods, Dr. Stewart found that latanoprost reduced IOP to a significantly greater degree than did timolol GFS (6.9 versus 6.2 mm Hg, p = 0.018).

The most common adverse events in both treatment groups were hyperemia (44%), blepharitis (17%), and erythema (11%). Four patients withdrew early, including two patients who withdrew because of potential drug-related adverse events: one patient taking latanoprost who developed conjunctival erythema and one taking timolol GFS who had increased heart rate and blood pressure.

Though the results of the study favored latanoprost, Dr. Stewart said both drugs retain a role in the treatment of glaucoma.

"Beta-blockers are still good medicine," he said. "Our best two classes of medication to reduce pressure in glaucoma are the beta-blockers and the prostaglandin analogs. Most studies seem to indicate that the prostaglandin analogs are more efficacious than the timolol solutions given twice daily. [Timolol GFS] is a once-daily beta-blocker, which provides dosing parity with latanoprost.