Fixed combinations of 0.2% brimonidine-0.5% timolol and 2% dorzolamide-0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine-timolol compared with dorzolamide-timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.
Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine-timolol BID or dorzolamide-timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79).
The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.
IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.
There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine-timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide-timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine-timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide-timolol (p = 0.213). Patients on brimonidine-timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide-timolol.
Fixed-combination brimonidine-timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide-timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine-timolol received higher ratings of ocular comfort than dorzolamide-timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine-timolol and dorzolamide-timolol during long-term treatment.
"In this study, it produced a further mean reduction of 5.4 mmHg (24.4%) when added to PGA monotherapy, demonstrating its usefulness as adjunctive hypotensive therapy. This activity is higher than that reported in previous studies of single-agent adjunctive therapy, in which mean IOP decreased by 5%–21%,11,12 and is within the range of other adjunctive fixed combination therapies (23.5%–29.3%).13 "
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to evaluate the safety and efficacy of adding a fixed combination of brinzolamide 1%/timolol 0.5% to prostaglandin analog (PGA) monotherapy in patients with primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension who require additional intraocular pressure (IOP) reduction.
This was a prospective, multicenter (n = 5), open-label, single-arm, Phase IV clinical trial in which patients currently being treated with a PGA but requiring additional IOP reduction were administered brinzolamide 1%/timolol 0.5% twice daily as adjunctive therapy to their current PGA monotherapy regimen. The primary objective was to examine the IOP-lowering efficacy of brinzolamide-timolol when used as adjunctive therapy.
Forty-seven patients enrolled in and completed the study. After 12 weeks of adjunctive brinzolamide-timolol therapy, the mean IOP of the total patient population decreased from 22.1 mmHg at baseline to 16.7 mmHg. The mean IOP reduction of 5.4 mmHg (24.4%) was both clinically and statistically significant (P < 0.001). This significant decrease in mean IOP at week 12 was maintained across all PGA groups (P < 0.05). No significant differences were observed in symptom frequency between baseline and week 12 for any of the six solicited symptoms. A total of 17 adverse events from six patients was reported, of which ten were drug-related. Most (n = 7) of the drug-related adverse events were mild or moderate in intensity. None of the adverse events required any treatment or resulted in treatment interruption or discontinuation. Of the 90 eligible eyes, 85.6% had a decrease in IOP of at least 3 mmHg from baseline and 98% of patients had a decrease in IOP of ≥1 mmHg.
This study suggests that a fixed combination of brinzolamide 1%/timolol 0.5% can provide additional IOP reduction effectively and safely when used as adjunctive therapy for patients receiving insufficient IOP reduction from PGA monotherapy.
"Some of the clinical studies conducted on dorzolamide–timolol fixed combination therapy beyond the marketing approval trials also had reports of systemic adverse events including: allergic reaction (0.7%38 and 1.1%45); benign atrial myxoma (0.7%);38 crystalluria (0.5%);11 dizziness (1.0%);28 dry mouth (2%);11 dyspnea (0.4%);39 eye discharge (2%);11 foreign body sensation (2%);11 headache (1.1%,45 1.6%,43 and 3%11); fatigue (1.1%);45 flu (3.1%);41 hyperglycemia (2%);11 lens opacity (5%);11 leukocytosis (3%);11 nausea (1.0%);28 oxaluria (0.5%);11 parathyroid hyperplasia (0.7%);38 pneumonia (0.7%);38 traumatic amputation of finger and thumb (0.7%);38 tremor (1.0%);28 upper respiratory infection (6%);11 and urolithiais (2.5%).11 In one comparative study, headache was reported more frequently in the latanoprost group than in the dorzolamide–timolol group (P = 0.04).33 "
[Show abstract][Hide abstract] ABSTRACT: Glaucoma is a collection of diseases characterized by multifactorial progressive changes leading to visual field loss and optic neuropathy most frequently due to elevated intraocular pressure (IOP). The goal of treatment is the lowering of the IOP to prevent additional optic nerve damage. Treatment usually begins with topical pharmacological agents as monotherapy, progresses to combination therapy with agents from up to 4 different classes of IOP-lowering medications, and then proceeds to laser or incisional surgical modalities for refractory cases. The fixed combination therapy with the carbonic anhydrase inhibitor dorzolamide hydrochloride 2% and the beta blocker timolol maleate 0.5% is now available in a generic formulation for the treatment of patients who have not responded sufficiently to monotherapy with beta adrenergic blockers. In pre- and postmarketing clinical studies, the fixed combination dorzolamide-timolol has been shown to be safe and efficacious, and well tolerated by patients. The fixed combination dorzolamide-timolol is convenient for patients, reduces their dosing regimen with the goal of increasing their compliance, reduces the effects of "washout" when instilling multiple drops, and reduces the preservative burden by reducing the number of drops administered per day.
"Ocular stinging/burning was significantly more common with fixed dorzolamide/timolol (9 patients) than with fixed brimonidine/timolol (1 patient, P = 0.027). In a randomized parallel-group comparison study, after 3 months of treatment the mean IOP was lower (15.6 vs 17.2 mmHg, P = 0.040) and the mean reduction from baseline IOP was greater (7.7 vs 6.7 mmHg, P = 0.040) in patients treated with FCBT monotherapy than in patients treated with FCDT monotherapy.33 On a comfort/tolerability questionnaire, patients treated with fixed brimonidine/timolol reported significantly less stinging (P < 0.001), burning (P = 0.015), and unusual taste (P = 0.005) compared with patients treated with fixed dorzolamide/timolol. "
[Show abstract][Hide abstract] ABSTRACT: Fixed combinations of medications that lower intraocular pressure (IOP) are increasingly used in the treatment of glaucoma and ocular hypertension and offer several potential advantages over combined use of the separate component medications including enhanced convenience, improved adherence, reduced exposure to preservatives, and possible cost savings. This review aims to examine the current role of IOP-lowering fixed combinations in disease management. The results of studies that compared the efficacy and safety of IOP-lowering fixed combinations with their component medications are summarized, including those fixed combinations that consist of a prostaglandin analog and timolol. The fixed combinations currently available for use in the United States are fixed-combination dorzolamide/timolol (FCDT) and fixed-combination brimonidine/timolol (FCBT). Both of these fixed combinations reduce IOP more effectively than their component medications used separately as monotherapy. FCBT therapy also demonstrates a more favorable safety profile and reduced ocular allergy compared to monotherapy with brimonidine, a component medication. Few studies have directly compared the efficacy and safety of FCDT and FCBT, but available evidence suggests that FCBT is at least as effective as FCDT in lowering IOP and is more comfortable and better tolerated. Additional studies are needed to further evaluate the comparative efficacy and tolerability of FCDT and FCBT in the management of glaucoma and ocular hypertension.
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