Fixed-combination Brimonidine-timolol Research Articles

Comparison of the Intraocular Pressure-Lowering Effect and Safety of Preservative-Free And Preservative-Containing Brimonidine/Timolol Fixed-Combination Ophthalmic Solutions in Patients with Open-Angle Glaucoma

ABSTRACT Purpose: To compare the therapeutic efficacy and safety of newly developed preservative-free (PF) brimonidine/timolol fixed-combination (BTFC) ophthalmic solutions and a preservative-containing (PC) BTFC ophthalmic solution in patients with open-angle glaucoma. Methods: This study was conducted as a multicenter, randomized, open-label, parallel-group clinical trial to evaluate the efficacy and safety of PF BTFC as compared with PC BTFC in adult patients (aged ≥ 19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). A total of the 106 patients were enrolled, with 53 patients each randomized to the two treatment groups and included in the analysis of the safety set (SS). After a washout period, patients with an IOP below 35 mmHg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, a total of 106 OAG and OHT patients were randomized to the PF group or PC group. All subjects were examined 4 and 12 weeks after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 11 a.m. and the efficacy, safety, and compliance were evaluated. Throughout the study, all adverse events were recorded and monitored by the investigators. Results The mean IOP changes from baseline to 12 weeks at 11:00 a.m. were −3.45 ± 2.53 mmHg in the PF group and −3.65 ± 2.76 mmHg in the PC group (p < .0001 for both). The difference in mean IOP change between the two groups was 0.20 ± 2.65 mmHg, which was not significantly different. The proportion of patients with IOP reductions of ≥ 15% and ≥ 20% and IOP at all-time points in the PF group were not significantly different when compared with in the PC group. There were no specific differences between the two groups regarding the incidence of adverse events. Conclusions PF BTFC ophthalmic solution shows a similar efficacy and safety profile to that of PC BTFC.

Comparative Study between the Effect of Dorzolamide/Timolol Fixed Combination and Brimonidine/Timolol Fixed Combination on Corneal Endothelium

Abstract Background: Glaucoma is one of the most important cause of irreversible blindness in the world. Elevated Intraocular Pressure (IOP) remains the main known risk factor for the development and progression of the disease. The main thera-peutic goal is to preserve visual function by reducing the IOP, which is the key modifiable risk factor. Aim of Study: Is to compare the effect and safety of Dorzolamide/Timolol-Fixed Combination (DTFC) and Bri-monidine/Timolol-Fixed Combination (BTFC), on corneal endothelium after 3 months. Patient and Methods: This comparative non-randomized controlled clinical trial study included 57 eyes of 57 patients which was conducted in Damietta Eye Hospital. Their age ranged from 20-70 years old. The study population was divided into two groups: First group receiving DTFC: Included 27 eyes of 27 patients with open angle glaucoma and second group receiving BTFC included 30 eyes of 30 patients with open angle glaucoma. Result: Show that this adjusted difference between group 1 and group 2 through 3 months follow-up had no statistical significance in all variables such as IOP (p=0.172), CCT (p=0.072) and CD (p=0.406). Conclusion: The patients that received two fixed-combination (dorzolamide/timolol) and (brimonidine/timolol) had no statistically significant effect on CCT and ECD after 3 months from using these drugs.

Comparison of brimonidine-timolol and dorzolamide-timolol in the management of intraocular pressure increase after phacoemulsification.

To compare the effectiveness of brimonidine/timolol fixed combination (BTFC) and dorzolamide/timolol fixed combination (DTFC) in the management of short-term intraocular pressure (IOP) increase after phacoemulsification surgery. Eighty eyes of 80 patients undergoing phacoemulsification and intraocular lens (IOL) implantation were randomly assigned into three groups. Group 1 consisted of 28 eyes and represented the control group. Group 2 consisted of 25 eyes undergoing phacoemulsification surgery and BTFC was instilled at the end of surgery. Group 3 consisted of 27 eyes undergoing phacoemulsification surgery and DTFC was instilled at the end of surgery. IOP was measured preoperatively and 6, 24h and 1wk postoperatively. There was no statistically significant difference in preoperative baseline IOP among the three groups (P=0.84). However, IOP was significantly lower in groups 2 and 3 compared to the control group (P<0.05 for all comparisons) at all postoperative visits. There was no significant difference between groups 2 and 3 at any visit. Eight eyes (28.6%) in the control group, two (8%) in Group 2 and one (3.7%) in Group 3 had IOP >25 mm Hg at 6h after surgery (P=0.008). However, IOP decreased and was >25 mm Hg in only one eye in each group at 24h after surgery. BTFC and DTFC have similar effects in reducing increases in IOP after phacoemulsification surgery and can both be recommended for preventing IOP spikes after such surgery.

Fixed Combination Brimonidine–Timolol Versus Brimonidine for Treatment of Intraocular Pressure Elevation After Neodymium:YAG Laser Posterior Capsulotomy

To evaluate the efficacy of fixed combination brimonidine-timolol (FCBT) in comparison with brimonidine tartrate 0.2% and control for the treatment of intraocular pressure (IOP) spikes after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. One hundred five eyes of 105 patients were enrolled in the study. Patients were randomized to 3 groups (each group, including 35 patients): the FCBT group that received 1 drop of FCBT, the brimonidine group that received 1 drop of brimonidine tartrate 0.2%, and the control group that received 1 drop of artificial tear, 1 h before the laser procedure. Postoperative IOP measurements were performed at 1st, 2nd, 3rd, 24th hours, and seventh day. The mean IOP changes from baseline were statistically different between the study groups at first, second, and third hours (all P<0.001). Pairwise comparisons showed that although the mean IOP changes of the treatment groups were similar at 1st and 24th hours and seventh day (all P>0.05), the IOP levels of the brimonidine group were less reduced from baseline than the FCBT group at second and third hours (P=0.01 and P=0.03, respectively). The differences among the study groups concerning the incidence of IOP elevations of ≥5 or ≥10 mmHg were statistically significant (P=0.007, P=0.04, respectively). However, the differences between the treatment groups were not statistically significant (both P>0.05). This study has shown that preoperative instillation of 1-drop FCBT was safe and effective for preventing IOP spikes after Nd:YAG laser posterior capsulotomy. FCBT may be a better option than brimonidine tartrate 0.2%, which is one of the current standard prophylaxes for these spikes.

Fixed-combination brimonidine–timolol versus latanoprost in glaucoma and ocular hypertension: a 12-week, randomized, comparison study

Objective:To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%–timolol 0.5% compared with latanoprost 0.005% in patients with glaucoma or ocular hypertension.Research design and methods:This was a prospective, randomized, multicenter, investigator-masked clinical trial. After washout of any previous IOP-lowering medications, patients with IOP of 24 mmHg or higher were randomized to twice-daily fixed-combination brimonidine 0.2%–timolol 0.5% (n = 73) or once-daily latanoprost 0.005% (n = 75, dosed in the evening, with vehicle control in the morning to maintain masking) for 12 weeks. IOP was measured at 8 a.m. (before dosing), 10 a.m., and 3 p.m. at baseline, week 6, and week 12.Clinical trial registration:The trial is registered with the identifier 00811564 at http://www.clinicaltrials.gov.Main outcome measures:The primary efficacy endpoint was diurnal IOP (averaged over 8 a.m., 10 a.m., and 3 p.m.) at week 12. Safety measures included biomicroscopy.Results:There was no statistically significant difference between the treatment groups in mean diurnal IOP at baseline (p = 0.118). At week 12, the mean (SD) diurnal IOP was 17.8 (2.9) mmHg with brimonidine–timolol and 17.9 (3.9) mmHg with latanoprost (p = 0.794). The percentage of patients achieving at least a 20% decrease from baseline diurnal IOP at week 12 was 87.7% in the brimonidine–timolol group and 77.3% in the latanoprost group (p = 0.131). Measured biomicroscopic changes from baseline to week 12 were infrequent in both groups.Conclusions:Fixed-combination brimonidine–timolol was as effective as latanoprost in reducing IOP in patients with glaucoma or ocular hypertension. Both treatments demonstrated favorable ocular tolerability. The duration of the study was 12 weeks, and additional studies will be needed to compare the efficacy and safety of fixed-combination brimonidine–timolol and latanoprost during long-term treatment.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG). One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy. Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P < 0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: -0.7 mm Hg, 95% confidence interval (CI): (-1.0, -0.3), P < 0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (-1.0 mm Hg, 95% CI (-1.6,-0.5), P = 0.001) and at 0200 (-0.9 mm Hg, 95% CI: (-1.4,-0.5), P = 0.001). No significant difference existed for the other time points. Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

Update on the role of alpha-agonists in glaucoma management

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine–purite formulations are preferred to brimonidine–benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine–timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

Control of intraocular pressure fluctuation: are combination drugs more effective?

Evaluation of: Spaeth GL, Bernstein P, Caprioli J, Schiffman RM. Control of intraocular pressure and fluctuation with fixed-combination brimonidine–timolol versus brimonidine or timolol monotherapy. Am. J. Ophthalmol. 151(1), 93–99.e4 (2011).Lowering intraocular pressure (IOP) is fundamental in the treatment of glaucoma, as it is the only therapy demonstrated to slow progression of disease. IOP fluctuation, however, may be more complex and its role in glaucoma is not clear. Recent advances have resulted in fixed-combination drugs, which improve compliance with better efficacy than monotherapy of the components separately. This study compares the effect of fixed-combination brimonidine–timolol to timolol alone and brimonidine alone on IOP lowering and IOP fluctuation. This article demonstrates that the fixed combination lowers IOP and reduces intraday (daytime) and interday fluctuation more than either component alone. The combination may be useful as a step therapy from either of the individual components.

Control of Intraocular Pressure and Fluctuation With Fixed-Combination Brimonidine–Timolol Versus Brimonidine or Timolol Monotherapy

To evaluate control of intraocular pressure (IOP) and IOP fluctuation in patients with ocular hypertension or glaucoma treated with fixed-combination brimonidine-timolol compared with brimonidine or timolol monotherapy. Post hoc analysis of data from 2 identical, 12-month, randomized, double-masked, multicenter trials. Patients were treated bilaterally with fixed brimonidine-timolol twice a day (n = 385), brimonidine tartrate 0.2% 3 times a day (n = 382), or timolol 0.5% twice a day (n = 392). Diurnal IOP was measured at follow-up visits at weeks 2 and 6 and months 3, 6, 9, and 12. IOP fluctuation was defined as the standard deviation of IOP measurements. The percentage of patients with mean diurnal IOP <18 mm Hg and short-term (daily) IOP fluctuation ≤2 mm Hg was statistically significantly higher in the brimonidine-timolol group than in the brimonidine or timolol group at each follow-up visit (at month 12, brimonidine-timolol 43.0%; brimonidine 18.9%, timolol 33.5%, P ≤ .017). At each hour (8 AM, 10 AM, 3 PM, and 5 PM), the percentage of patients with mean IOP <18 mm Hg and long-term (intervisit) IOP fluctuation ≤2 mm Hg was statistically significantly higher with brimonidine-timolol than with brimonidine or timolol alone (at 8 AM, brimonidine-timolol 41.0%, brimonidine 11.3%, timolol 23.7%, P < .001). Patients treated with fixed-combination brimonidine-timolol were more likely than patients treated with either brimonidine or timolol alone to achieve a combination of low mean IOP and low short-term (daily) or long-term (intervisit) IOP fluctuation.

Considerations in glaucoma therapy: fixed combinations versus their component medications

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.

Twenty-four-hour efficacy of the brimonidine/timolol fixed combination versus therapy with the unfixed components

To evaluate the 24-h intraocular pressure (IOP) control of brimonidine/timolol fixed combination (BTFC) versusthe unfixed combination of its individual components, each dosed twice daily, in patients with primary open-angle glaucoma or ocular hypertension. An observer-masked, randomized, crossover, active-controlled, two-centre comparison. Following a 6-week medicine-free period, patients were randomized to BTFC or to the unfixed combination of brimonidine and timolol for 3 months. Patients then were crossed over to the opposite treatment for another 3 months. At the end of the medicine-free period, and each treatment period, patients underwent 24-h IOP measurements at 0600, 1000, 1400, 1800, 2200, and 0200 hours. Twenty-eight patients completed this study. Both BTFC and the unfixed components showed a significant IOP reduction from untreated baseline (P<0.0001), and were statistically equal when compared directly, for each individual time point and for the 24-h IOP curve (P>0.05). The mean 24-h IOP was 24.6+/-1.9 for baseline, 19.2+/-1.9 for BTFC, and 19.2+/-1.6 mmHg for the unfixed components (P=1.0). Four patients were discontinued due to side effects. The most common ocular adverse event was ocular hyperaemia (n=3 with BTFC and n=5 with the unfixed components, P=0.7) and systemic adverse events were rare. This study suggests that both BTFC and the unfixed components of brimonidine and timolol provide a significant 24-h IOP reduction from untreated baseline, and statistically equal control when compared directly, at each time point and for the 24-h pressure curve.

Comparing the fixed combination brimonidine-timolol versus fixed combination dorzolamide-timolol in patients with elevated intraocular pressure

ABSTRACTPurpose: To evaluate the efficacy of fixed combination brimonidine-timolol (FCBT) versus fixed combination dorzolamide-timolol (FCDT) given twice daily in patients with primary open angle glaucoma (POAG) or ocular hypertension (OH).Design: Prospective, multicentre, masked-observer, crossover comparison.Participants: Sixteen patients with POAG and 14 with OH.Methods: The participants of the study were washed out from their previous medication and randomized to fixed FCBT or FCDT for the first 4‑week treatment period. Subjects then were washed for 4 weeks and started on the opposite medication forthe second 4‑week period. Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer at 8:00 a.m., 12:00 noon and 4:00 p.m. at each baseline and at the end of each treatment period. Unsolicited ocular adverse events were also recorded.Main outcome measures: Comparison of the IOP lowering effect of FCBT and FCDT.Results: The baseline mean diurnal IOP for all 30 subjects (30 eyes) was 22.9 ± 1.6 mmHg. Both fixed combinations significantly reduced IOP compared with baseline ( p < 0.00001). The mean diurnal IOP following 4 weeks of therapy was 15.0 ± 2.1 mmHg for FCBT and 15.4 ± 2.1 mmHg for FCDT ( p = 0.510). The mean diurnal IOP reduction was 7.8 ± 1.9 mmHg for FCBT and 7.4 ± 1.8 mmHg for FCDT ( p = 0.430). Overall, 14 subjects complained about ocular adverse events: two only for FCBT, seven only for FCDT and five for both drugs. Although there was no significant difference between the number of subjects that reported ocular adverse events with FCBT (n = 7) and FCDT (n = 12) ( p = 0.359), FCDT caused more ocular stinging upon instillation (n = 9) than FCBT (n = 1) ( p = 0.027).Conclusion: This study suggests that FCBT and FCDT, each given twice daily, have similar efficacy in patients with POAG or OH.