Efficacy and safety of once-daily levobunolol for glaucoma therapy

We studied the ocular hypotensive efficacy and safety of 0.5% levobunolol hydrochloride and 0.5% timolol maleate administered topically once daily for 3 months in 91 patients (46 in the levobunolol group and 45 in the timolol group) with primary or secondary open-angle glaucoma or ocular hypertension. In this randomized double-masked parallel clinical study, intraocular pressure (IOP) was successfully controlled in 78% of the patients who received levobunolol and 89% of those who received timolol. The overall mean decrease in IOP was 5.6 mm Hg (decrease of 23%) in the levobunolol group and 6.7 mm Hg (26%) in the timolol group, a nonsignificant difference. In both groups the overall mean IOP during treatment was significantly lower than the pretreatment value (p less than 0.001). For both treatment groups changes in heart rate and blood pressure were minimal. We conclude that both 0.5% levobunolol and 0.5% timolol administered once daily are effective and safe in lowering IOP in most patients with ocular hypertension or open-angle glaucoma.     

Levobunolol and betaxolol. A double-masked controlled comparison of efficacy and safety in patients with elevated intraocular pressure

In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension. During the 3-month study, intraocular pressure (IOP) reductions in the two levobunolol groups were significantly greater than in the betaxolol group. From a mean baseline IOP of approximately 25 mmHg, overall mean reductions were 6.2 and 6.0 mmHg for the 0.25 and 0.5% levobunolol groups, respectively, and 3.7 mmHg for the betaxolol group. No clinically or statistically significant among-group differences were noted in the systemic safety variables evaluated. These data suggest that although all three treatments are effective, levobunolol provides a greater reduction in IOP than betaxolol.     

Long-term ocular hypotensive effect of levobunolol: results of a one-year study.

Data for the first 12 months are reported for an ongoing, multicentre, clinical study comparing the long-term, ocular hypotensive efficacy and safety of topical levobunolol (0.5% and 1%) and timolol (0.5%). This study was a double-masked trial testing 88 patients with chronic open angle glaucoma or ocular hypertension. During the 12-month period drops were instilled twice daily into both eyes after a washout of prestudy ocular hypotensive medication. The effect of the three treatments in reducing intraocular pressure (IOP) was similar. Mean IOP reductions over the 12 months averaged 7.2 mmHg for the 0.5% levobunolol group, 6.2 mmHg for the 1% levobunolol group, and 6.0 mmHg for the timolol group. Decreases in mean heart rate of up to 5 beats per minute were observed in the 0.5% levobunolol group, up to 8 beats per minute in the 1% levobunolol group, and up to 4 beats per minute in the timolol group. Several patients were removed from the study owing to side effects possibly related to levobunolol treatment.     

Levobunolol and metipranolol: comparative ocular hypotensive efficacy, safety, and comfort.

Topical levobunolol 0.5% was compared with topical metipranolol 0.6% for efficacy, safety, and comfort in 46 patients with open angle glaucoma or ocular hypertension. The study was of parallel design, randomised, double-masked, and of three months' duration. After a washout interval the study medications were instilled twice daily in both eyes. The overall mean decrease in intraocular pressure (IOP) was approximately 7 mmHg in both groups. More than 90% of patients in both groups successfully completed the study. Both agents caused slight decreases in heart rate and blood pressure. More complaints of burning and stinging were reported in the metipranolol group than in the levobunolol group. This three-month, 46-patient study showed levobunolol 0.5% and metipranolol 0.6% to be similarly effective ocular hypotensive agents.     

Prophylactic treatment of intraocular pressure elevations after neodymium: YAG laser posterior capsulotomies and extracapsular cataract extractions with levobunolol

The prophylactic effect of topical 0.5% levobunolol on intraocular pressure (IOP) elevations after neodymium:YAG (Nd:YAG) laser posterior capsulotomies and extracapsular cataract extractions (ECCEs) was investigated in two separate, double-masked, placebo-controlled studies. In study 1, 42 patients received either levobunolol or vehicle 1 hour before a unilateral Nd:YAG laser posterior capsulotomy. Elevated IOP (greater than or equal to 10 mmHg) occurred in up to 38% of those in the vehicle group and none in the levobunolol group. Mean IOP increased up to 6 mmHg in the vehicle group, whereas it decreased up to 3 mmHg in the levobunolol group. In study 2, 41 patients received either levobunolol or vehicle immediately after a unilateral ECCE involving the use of a viscoelastic preparation and the implantation of a posterior chamber intraocular lens (PC IOL). The incidence of IOP elevations (greater than or equal to 10 mmHg) was up to 40% in the vehicle group and 19% in the levobunolol group. Mean IOP increased up to 9 mmHg in the vehicle group and up to 2 mmHg in the levobunolol group. Thus, marked elevations in IOP after posterior capsulotomies or ECCEs may be minimized by prophylactic treatment with levobunolol.     

A comparison of the ocular hypotensive efficacy of once-daily and twice-daily levobunolol treatment

The authors compared the ocular hypotensive efficacy of two different treatment regimens of levobunolol 0.5% in a double-masked, randomized, controlled clinical trial. Seventy-one patients with open-angle glaucoma or ocular hypertension received levobunolol 0.5% as their sole glaucoma medication either on a once-daily or twice-daily treatment regimen for 3 months. Approximately 81% of the patients in the once-daily treatment group and 88% of subjects in the twice-daily treatment group successfully completed the 3-month study period. The overall mean decrease in intraocular pressure (IOP) was 4.5 mmHg in the once-daily group and 5.6 mmHg in the twice-daily group. These differences were not statistically different. For both treatment groups, effects on mean heart rate and blood pressure were minimal. The authors' data from this population suggest that once-daily treatment with levobunolol is an effective glaucoma regimen.     

Levobunolol: A Beta-adrenoceptor Antagonist Effective in the Long-term Treatment of Glaucoma

We compared the ocular-hypotensive efficacy and systemic and ocular safety of an ophthalmic solution of levobunolol (0.5% and 1%) twice daily, with timolol (0.5%) twice daily in a long-term, double-masked study of 391 patients with open-angle glaucoma or ocular hypertension. Patients received the test medication in both eyes for up to two years. Over the two-year period, both concentrations of levobunolol reduced mean IOP by 27% (range, ?6 to ?8 mmHg). This ocular-hypotensive effect was sustained throughout the study and was similar to that produced by timolol. Slight decreases in mean heart rate and blood pressure were observed. No unexpected adverse ocular or systemic reactions were reported. The results of these studies indicate that levobunolol is an effective therapy for the long-term treatment of glaucoma.     

A comparison of the ocular hypotensive efficacy of twice-daily 0.25% levobunolol to 0.5% timolol in patients previously treated with 0.5% timolol

Treatment with noncardioselective beta-adrenoceptor antagonists (e.g., 0.5% timolol or 0.5% levobunolol) is standard practice for lowering elevated intraocular pressure (IOP). However, because there are risks and side effects associated with the use of these agents, a lower, yet still effective, dose may be preferred. We gave 0.5% timolol twice daily for 30 days to 143 patients. In a double-masked, randomized fashion, we then assigned patients to continue to receive 0.5% timolol twice daily or 0.25% levobunolol twice daily for 8 weeks. The mean unmedicated baseline IOP for both groups was approximately 25 mm Hg. After 30 days of timolol pretreatment, the mean IOP in both groups decreased to approximately 19 mm Hg (p = 0.210). After the 30-day timolol pretreatment period, and subsequent randomization to either 0.5% timolol or 0.25% levobunolol treatment, there was little change in overall mean IOP (0.03 mm Hg decrease for levobunolol, 0.06 mm Hg increase for timolol; p = 0.811) from the timolol pretreatment baseline. One patient assigned to the timolol treatment group was terminated from the study due to inadequate control of IOP. We conclude that the mean IOP lowering effect of 0.25% levobunolol is equivalent to 0.5% timolol, and switching patients from twice-daily 0.5% timolol to twice-daily 0.25% levobunolol poses no significant risk of decreased ocular hypotensive efficacy.     

Levobunolol compared with timolol: a four-year study.

Fifty-one patients with raised intraocular pressure (IOP) were treated for up to four years with one of three ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. The study was conducted as a double-masked, randomised trial in which medications were administered twice daily to both eyes. Levobunolol and timolol were equally effective in reducing overall mean IOP; reductions were greater than 8.8 mmHg in all three treatment groups. The study showed levobunolol to be as safe and effective as timolol in the long-term control of raised IOP.     

A comparison of the efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD and 0.5% levobunolol hydrochloride BID in patients with ocular hypertension or open-angle glaucoma.

The purpose of this study was to compare the ocular hypotensive efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol gel) and 0.5% levobunolol hydrochloride (levobunolol). This was a randomized, double-masked, multi-center, active-controlled, 2-period, crossover study. After a 3-week, single-masked placebo run-in phase, patients with ocular hypertension or open-angle glaucoma and an intraocular pressure (IOP) > or = 22 mmHg were randomized to receive timolol gel QD or levobunolol BID for 6 weeks followed by a 3-week, placebo washout period. Patients were then crossed over to the alternate treatment for 6 weeks. IOP and heart rate (HR) were measured at 3 and 6 weeks after the start of therapy with either timolol gel or levobunolol. Of 133 patients randomized, 116 received both treatments. Timolol gel QD was comparable to levobunolol BID in reducing trough and peak IOP. At trough, HR was marginally increased with timolol gel and was decreased with levobunolol (p = < 0.001). At peak, HR was decreased with both treatments, but the decrease was significantly less with timolol gel than with levobunolol (p = 0.049). Significantly more patients experienced at least one adverse event (p = 0.024), adverse events related to special senses (p = 0.002), and burning and stinging (p < 0.001) with levobunolol compared to timolol gel. The study demonstrates that timolol gel QD has IOP-lowering effects comparable to those of levobunolol BID with fewer adverse experiences and less effect on HR.     

Efficacy and safety of topical oxymetazoline in treating allergic and environmental conjunctivitis

This randomized, double-masked study evaluated the safety and efficacy of oxymetazoline 0.025% topical ophthalmic solution compared with its vehicle when used to treat allergic or environmental conjunctivitis. Thirty-nine patients with moderate bilateral conjunctival hyperemia instilled one drop of either oxymetazoline 0.025% solution or its vehicle twice daily for one week. At each evaluation the signs and symptoms of conjunctivitis were evaluated, complete eye examinations were performed, and heart rate and blood pressure were measured. An overall assessment of treatment efficacy was made at each follow-up evaluation. The signs and symptoms of conjunctivitis had significantly improved in the oxymetazoline-treated group when compared with those of the vehicle-treated group, and the ocular and systemic safety of each treatment was comparable.     

Evaluation of once-daily levobunolol 0.25% and timolol 0.25% therapy for increased intraocular pressure

In a three-month, double-masked, randomized clinical trial, we evaluated the once-daily ocular hypotensive efficacy of 0.25% levobunolol and 0.25% timolol in 80 patients with open-angle glaucoma or ocular hypertension. Thirty-seven of the 39 patients (95%) in the 0.25% levobunolol group and 35 of the 41 patients (85%) in the 0.25% timolol group successfully completed the three-month study period. The overall mean decrease in intraocular pressure was 5.3 mm Hg (22%) in the 0.25% levobunolol group and 5.4 mm Hg (22%) in the 0.25% timolol group. This difference was not statistically significant. In both treatment groups, effects on mean heart rate and blood pressure were minimal. The data suggest that levobunolol 0.25% and timolol 0.25%, administered once daily, are equally effective in the treatment of open-angle glaucoma and ocular hypertension.     

Effects of systemic beta-blocker therapy on the efficacy and safety of topical brimonidine and timolol. Brimonidine Study Groups 1 and 2

PURPOSE: To determine the impact of coadminstration of systemic beta-blockers on the ocular hypotensive efficacy and safety of topical timolol, a nonselective, beta-blocker, and that of brimonidine, an alpha2-selective adrenergic agonist, in patients with glaucoma or ocular hypertension. DESIGN: Post hoc evaluation of data collected from two prospective, multicenter, randomized, double-masked, parallel-group, actively-controlled, 12-month clinical trials. PARTICIPANTS: Of the 926 subjects with ocular hypertension or glaucoma that were enrolled in the two prospective trials, 66 (7.1%) were concurrently maintained on systemic beta-blocker therapy. Of these patients, 34 had been assigned to the brimonidine group and 32 to the timolol group. METHODS: Subjects instilled into each eye either 1 drop of brimonidine 0.2% or timolol 0.5% twice daily for 1 year. Study subjects within medication treatment groups were classified as to their use or nonuse of concurrent systemic beta-blockers, and mean intraocular pressure (IOP) reduction, adverse events, heart rate, and blood pressure were compared. MAIN OUTCOME MEASURES: Mean IOP reduction from baseline was the primary efficacy variable. Adverse events and mean changes in heart rate and blood pressure from baseline were the primary safety variables. RESULTS: Timolol-treated subjects concurrently taking systemic beta-blockers had smaller decreases in IOP, a greater mean change in systolic (at week 2, months 1, 2, 6, and 9; P < or = 0.001) and diastolic blood pressure (months 2 and 6; P < or = 0.02), and a significantly greater mean decrease in heart rate (month 6; P = 0.004) compared with timolol subjects not taking systemic beta-blockers. By contrast, there was a modest enhancement of IOP-lowering efficacy at trough and no effect on blood pressure or heart rate in brimonidine-treated subjects who were concurrently receiving systemic beta-blocker therapy compared with brimonidine subjects not receiving systemic beta-blockers. CONCLUSIONS: Concurrent systemic beta-blocker therapy had no deleterious effect on ocular hypotensive efficacy and no impact on systemic safety parameters with topical brimonidine, whereas efficacy was reduced and systemic safety parameters were impacted with topical timolol. Ocular hypotensive agents other than beta-blockers, such as the alpha2 agonist brimonidine, may be a more appropriate first-line therapy for ocular hypertension and glaucoma patients concurrently taking systemic beta-blockers.     

Brimonidine 0.15% versus apraclonidine 0.5% for prevention of intraocular pressure elevation after anterior segment laser surgery

PURPOSE: To compare the efficacy and safety of brimonidine 0.15% with those of apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. SETTING: Massachusetts Eye and Ear Infirmary, Glaucoma Service, Boston, Massachusetts, USA. METHODS: This double-masked randomized trial 80 eyes of 80 patients who had laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:YAG laser capsulotomy. Eyes received 1 drop of brimonidine 0.15% or apraclonidine 0.5% before laser surgery. Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before laser treatment, 41 patients received brimonidine 0.15% and 39 received apraclonidine 0.5%. Thirteen (31.7%) patients in the brimonidine group and 11 (28.2%) in the apraclonidine group had postoperative IOP elevations of 5 mm Hg or more (P = .5). Four patients (9.8%) in the brimonidine group and 3 (7.7%) in the apraclonidine group had IOP increases of 10 mm Hg or more (P = .5). There were no statistically significant changes in mean heart rate or blood pressure in either group except a slight reduction in diastolic blood pressure at 1 hour in the brimonidine group (-4.7 +/- 9.2 mm Hg) compared with that in the apraclonidine group (-0.1 +/- 9.1 mm Hg) (P = .01). No clinically significant side effects were noted in either group. CONCLUSION: A single preoperative drop of brimonidine 0.15% had similar efficacy and safety as apraclonidine 0.5% in preventing IOP elevations immediately after anterior segment laser surgery.     

Levobunolol compared with timolol for the control of elevated intraocular pressure

Two concentrations of levobunolol (0.5% and 1%) and one concentration of timolol (0.5%) were evaluated for the control of elevated intraocular pressure (IOP) in a double-masked, randomized study. Fifty-one patients received one of the three study treatments in both eyes bid for one year. Both drugs were equally effective in reducing IOP: The overall reduction in mean IOP was slightly more than 9 mm Hg in all three treatment groups. Levobunolol was as safe and effective as timolol for the long-term control of elevated IOP.     

A clinical evaluation of the effects of topically applied levobunolol and timolol on increased intraocular pressure

Data from two short-term double-masked studies using 24 and 16 subjects suggest that topically applied levobunolol safely and effectively treats open-angle glaucoma and ocular hypertension. The onset of effect of a single drop of 0.5% levobunolol occurred within the first hour, producing a maximal hypotensive effect of more than 8 mm Hg after two hours. An intraocular pressure deceased of greater than or equal to 2 mm Hg was still observed after 24 hours for both concentrations of levobunolol tested (0.5% and 1%). Intraocular pressure decreases of more than 9 mm Hg persisted during a one-month trial in which patients were treated twice daily, confirming the results obtained in the 24-hour study. Systemic effects of both timolol (0.5%) and levobunolol (0.5% and 1%) included a consensual intraocular pressure-decreasing effect in the untreated eye and clinically significant reductions in heart rate. Diastolic blood pressure was decreased at two and four hours after administration of 0.5% levobunolol.     

Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study.

The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.     

Comparison of the effectiveness and safety of levobunolol and timolol in ocular hypertension and chronic open-angle glaucoma

Twenty-six patients with open-angle glaucoma or ocular hypertension were studied in a concomitant double-masked clinical trial lasting three months, in which the ocular hypotensive efficacy and safety of levobunolol (0.5%) and timolol (0.5%), topically administered twice daily, were compared. At all follow-up examinations there was a significant decrease in mean intraocular pressure from baseline in both treatment groups, with no significant difference between them in this regard. Few changes were seen in either treatment group in cup/disk ratio, visual fields, visual acuity, biomicroscopy, or ophthalmoscopy. In both groups slight decreases in mean blood pressure were observed. Levobunolol and timolol were similarly effective and safe in reducing intraocular pressure in patients with chronic open-angle glaucoma and those with ocular hypertension.     

The safety and efficacy of travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution

PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution (Trav/Tim) to its components travoprost 0.004% ophthalmic solution, TRAVATAN, (Trav) and timolol 0.5% ophthalmic solution (Tim) in patients with open-angle glaucoma or ocular hypertension. DESIGN: Randomized multicenter, double-masked, active-controlled, parallel group study. METHODS: Two hundred sixty-three patients with open-angle glaucoma or ocular hypertension were randomized to receive Trav/Tim once daily AM (and vehicle PM), Trav once daily PM (and vehicle AM), or Tim twice daily (AM and PM). Efficacy and safety were compared across treatment groups over 3 months. RESULTS: Trav/Tim produced a mean IOP decrease from baseline of 1.9 mm Hg to 3.3 mm Hg more than Tim, with a significant decrease in mean IOP at each of the nine study visits (P < or = .003). Trav/Tim decreased mean IOP by 0.9 mm Hg to 2.4 mm Hg more than Trav, with a significant decrease in mean IOP at seven of the nine study visits (P < or = .05). The adverse event profile for Trav/Tim was comparable to Trav or Tim alone. CONCLUSIONS: Over the 3 months of treatment, Trav/Tim produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by either Trav or Tim alone. The clinical results that Trav/Tim was safe and well tolerated with an incidence of adverse events was comparable to the results of Trav or Tim alone. Trav/Tim provides both more effective IOP reduction than its components and the benefits of once-daily dosing.     

Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel

PURPOSE: The objective of this randomized, double-blind, controlled crossover trial was to compare 0.1% timolol hydrogel formulation eyedrops with 0.5% timolol aqueous solution in terms of systemic effects, hypotensive efficacy and pharmacodynamics. METHODS: Twenty-four healthy subjects underwent careful ocular, cardiovascular and pulmonary function evaluation before and after 2 weeks of topical treatment with 0.1% timolol hydrogel or 0.5% aqueous timolol maleate. Intraocular pressure (IOP), heart rate, blood pressure, forced expiratory volume and plasma levels of timolol were measured. RESULTS: There was a statistically significant difference in the systemic absorption of timolol between these two ophthalmic timolol solutions. The peak concentration and mean area under the plasma drug concentration-time curve (AUC) were about 10-fold higher after 0.5% timolol aqueous solution. The mean peak heart rate during exercise was reduced by 19 bpm (SD 6.4 bpm) after 0.5% timolol aqueous solution and by only 4.6 bpm (SD 3.8 bpm) after 0.1% timolol hydrogel (p < 0.0001). There was no difference between the two formulations in efficacy in reducing IOP. No differences between treatments were found in respect of pulmonary function. CONCLUSIONS: The lower timolol concentration in the hydrogel vehicle and its better bioavailability resulted in reduced systemic absorption and side-effects without loss of efficacy.