Use of fixed-combination dorzolamide 2.0% and timolol 0.5% (dorzolamide-timolol; Cosopt, Merck) as a replacement or add-on is a safe and effective option to achieve further IOP lowering in patients.
Montreal-Use of fixed-combination dorzolamide 2.0% and timolol 0.5% (Cosopt, Merck) as a replacement or add-on is a safe and effective option to achieve further IOP lowering in patients whose glaucoma has not responded adequately to prostaglandin analogue monotherapy, according to the results of a Phase IV, "real-world" study undertaken by Canadian researchers.
"Phase IV studies are required to determine whether the results observed in controlled clinical trials can be extrapolated to the less controlled, real-life setting. In Phase IV studies, patients typically represent those who are treated by physicians in routine practice, with less-selective inclusion criteria and stringent follow-up schedules when compared with controlled clinical trials," said John S. Sampalis, PhD, the corresponding author of the published paper reporting the study [Ann Pharmacother 2008;42:498-504].
The prospective, multicenter, open-label, cohort study was designed to evaluate treatment outcomes in routine clinical practice. It involved the participation of 33 community-based ophthalmologists who enrolled 350 patients with primary open-angle glaucoma or ocular hypertension. Eligible patients had to have been taking latanoprost 0.005% (Xalatan, Pfizer) monotherapy for a minimum of 4 weeks and either had IOP >21 mm Hg, deterioration of the visual field, had medication failure to reach target IOP, or experienced less than 15% IOP-lowering. The decision to add or switch therapy was based on the response to latanoprost monotherapy. Patients who qualified for the Phase IV study because their IOP was lowered less than 15% by latanoprost monotherapy were switched to dorzolamide-timolol (70 patients). Patients who were entered based on any of the three other inclusion criteria received dorzolamide-timolol as add-on therapy (280 patients). Dorzolamide-timolol was administered twice daily, and patients continuing with latanoprost used their medication once daily as originally prescribed. Change from baseline IOP was assessed after 6 and 12 weeks, with the 12-week outcome used for the primary effectiveness outcome measure. For each patient, all visits were conducted in the morning at approximately the same time, and patients were instructed to administer their medication approximately 2 hours prior to their visit time. Mean baseline IOP was 21.89 mm Hg in the add-on group and 22.74 mm Hg in the switch group. After 6 weeks, mean IOP was significantly (p < 0.001) reduced in both the patients who used dorzolamide-timolol as an adjunct (–6.01 mm Hg, –26.7%) and in those who switched to the fixed combination (–5.20 mm Hg, –20.77%). Mean IOP remained stable at 12 weeks in both groups and was still significantly reduced from baseline in the add-on (–6.3 mm Hg, -28%) group and in the patients who switched therapy (–5.8 mm Hg, –23.5%). Two-thirds of patients in the add-on group were categorized as therapeutic responders, based on achieving an IOP reduction of greater than 20%, as were 52.9% of patients in the switch group.
The fixed-combination treatment was well tolerated. About one-fourth of patients reported adverse events attributed to their medication. Most of the events were mild and nonserious, but 23 patients (6.5%) withdrew from the study because of adverse events. Eye irritation (12%) and taste perversion (4.3%) were most common.
Adherence also was investigated and was found to be relatively high: about 70% of patients in each group reported missing no doses of dorzolamide-timolol. For dorzolamide-timolol, the mean number of doses missed was 7.9% at 6 weeks and 2.7% a 12 weeks. Patients reported missing 5.0% of their latanoprost doses at 6 weeks and 4.2% of doses at 12 weeks.
"Even after allowing for the potential bias of self-reported adherence, the compliance results are satisfactory," Sr. Sampalis aid. "Furthermore, the results demonstrating that the use of fixed-combination dorzolamide-timolol as a replacement or add-on produced significant reductions in IOP supporting the observation of high compliance with treatment," Dr. Sampalis said.