Fixed, unfixed combo therapies reduce IOP similarly

August 1, 2005

Fort Lauderdale, FL—The fixed combination of dorzolamide hydrochloride-timolol maleate (Cosopt, Merck) and the unfixed combination of latanoprost (Xalatan, Pfizer Ophthalmics) and timolol (Timop-tic, Merck) reduce IOP to a similar degree in patients with glaucoma, according to a small clinical study reported at the Association for Research in Vision and Ophthalmology (ARVO).

Fort Lauderdale, FL-The fixed combination of dorzolamide hydrochloride-timolol maleate (Cosopt, Merck) and the unfixed combination of latanoprost (Xalatan, Pfizer Ophthalmics) and timolol (Timop-tic, Merck) reduce IOP to a similar degree in patients with glaucoma, according to a small clinical study reported at the Association for Research in Vision and Ophthalmology (ARVO).

Both therapies significantly reduced IOP from baseline, and the mean reduction was 1.3 mm Hg with both treatments.

"Many papers have been published about fixed combinations of medications, especially new combinations," said Grace Lee, MD, a glaucoma specialist affiliated with Kaiser Permanente, Woodland Hills, CA. "We wanted to see whether the fixed combination of dorzolamide-timolol, which is the most commonly prescribed fixed combination, is different from treatment with the separate drugs latanoprost and timolol. We found that the two treatments resulted in equivalent decreases in IOP."

"Sometimes noncompliance with treatment is due to an increased number of medications, although we didn't specifically evaluate compliance in our study," said Dr. Lee, who was a glaucoma fellow at the Wills Eye Hospital at Jefferson Medical College, Philadelphia, when the study was conducted.

The two combination therapies were compared in a randomized, crossover clinical trial involving 48 eyes in 29 patients. Patients with primary open-angle, normal-tension, and pseudoexfoliative glaucoma were prospectively screened. Age, gender, race, diagnosis, visual acuity, applanation tonometry, time of day, and adverse effects were recorded by an examiner who was blinded to the treatment.

All patients began treatment with timolol monotherapy at the initial screening visit and continued for a minimum of 4 weeks. Then, patients were randomly assigned to fixed-combination dorzolamide-timolol or the unfixed combination of latanoprost plus timolol and treated for a minimum of 4 weeks. Upon completion of the randomized therapy, patients received timolol alone for a 4-week washout period, followed by crossover to the opposite therapy and treatment for an additional 4 weeks. IOP was recorded after 4 weeks of treatment.

Baseline IOP averaged 17.5 mm Hg for patients who began randomized treatment with the fixed combination and 17.3 mm Hg for patients who began randomized treatment with latanoprost plus timolol. The fixed combination of dorzolamide-timolol resulted in a mean IOP decrease of 1.3 ± 3 mm Hg, which was a significant change from baseline (p = 0.004). The combination of latanoprost and timolol also led to an average decrease of 1.3 ± 2.7 mm Hg from baseline (p = 0.002). The difference between the two treatments was not statistically significant.

"The results might suggest that the fixed combination of dorzolamide-timolol may have similar efficacy to the separate medications latanoprost and timolol," Dr. Lee said.

Other investigational studies The study follows other recent investigations that have evaluated fixed-combination therapy and unfixed combinations. One study found that significant IOP lowering resulted when latanoprost or dorzolamide was added to timolol. However, latanoprost had greater additive reduction in diurnal IOP compared with dorzolamide (J Glaucoma 2001;10:316-324).

Another study found that fixed combinations of latanoprost-timolol and dorzolamide-timolol both lowered diurnal IOP from baseline, but latanoprost-timolol was slightly more efficacious (Ophthalmology 2004;111:276-282).

Monotherapy with latanoprost demonstrated IOP-lowering efficacy similar to that of the fixed combination of dorzolamide-timolol in a comparison of the two therapies (Acta Ophthalmologica Scandinavica 2002;80:635-641). An evaluation of the fixed combination of latanoprost-timolol did not lower IOP more than its component parts (Br J Ophthalmol 2004;88: 199-203).

The results of the current study are noteworthy because of the plethora of fixed combinations that are being proposed, said Dr. Lee and co-investigator L. Jay Katz, MD, co-director of the glaucoma service at Wills Eye Hospital and professor of ophthalmology at Jefferson Medical College. The study might not have demonstrated a difference between the treatments because of the small number of patients involved. Additionally, the patients had a lower baseline IOP compared with other studies.