The Experts below are selected from a list of 3198 Experts worldwide ranked by ideXlab platform
Ingrid Adamsons - One of the best experts on this subject based on the ideXlab platform.
-
A randomized trial assessing Dorzolamide in patients with glaucoma who are younger than 6 years.
Archives of ophthalmology (Chicago Ill. : 1960), 2005Co-Authors: Elyssa Z. Ott, Monte D. Mills, Santiago Arango, Albert J. Getson, Christopher A. Assaid, Ingrid AdamsonsAbstract:Objective To evaluate Dorzolamide hydrochloride in patients younger than 6 years who have an elevated intraocular pressure or glaucoma. Design A 3-month, controlled, randomized, double-masked, multicenter, clinical trial. Patients were randomized to 2% Dorzolamide 3 times daily or timolol maleate gel-forming solution (0.25% for patients Results One younger patient (1.8%) of 56 randomized to Dorzolamide discontinued concomitant therapy because of bradycardia. Two older patients (3.0%) of 6. discontinued Dorzolamide because of ocular adverse experiences. The most frequent ocular adverse experiences were discharge and ocular hyperemia (younger cohort. and ocular hyperemia and burning/stinging (older cohort). At week 12, the mean change in intraocular pressure for Dorzolamide was statistically significant from baseline (−7.3 mm Hg [−20.6%] and −7.1 mm Hg [−23.3%]) in the younger and older cohorts, respectively;P Conclusion Dorzolamide was generally well tolerated and demonstrated efficacy for up to 3 months in patients younger than 6 years.
-
efficacy and tolerability of the Dorzolamide 2 timolol 0 5 combination cosopt versus 0 005 xalatan in the treatment of ocular hypertension or glaucoma results from two randomized clinical trials
Acta Ophthalmologica Scandinavica, 2004Co-Authors: Robert D Fechtner, Albert J. Getson, Juhani P Airaksinen, Christopher Lines, Ingrid AdamsonsAbstract:. Purpose: To compare the efficacy of the fixed Dorzolamide 2%/timolol 0.5% combination (COSOPT™) versus latanoprost 0.005% (XALATAN™). Methods: Two 3-month, parallel group, randomized, observer-masked and patient-masked, multicentre, clinical trials were performed in patients with ocular hypertension or open-angle glaucoma. Study 1 (n = 256) was conducted in the United States and Study 2 (n = 288) was conducted in Europe/Israel. Patients could be included whether or not they were currently taking ocular hypotensive therapy, and regardless of the effectiveness of any previous therapy. Patients were washed out from their usual ocular hypotensive medications and then those with a baseline intraocular pressure (IOP) ≥ 24 mmHg were randomized to either the Dorzolamide/timolol combination eye drops twice daily or latanoprost eye drops once daily in both eyes. Efficacy was assessed by daytime diurnal IOP (the mean of measurements made at 0800, 1000, 1400 and 1600 h). Results: At baseline, the mean daytime diurnal IOP was 26.1 mmHg in the Dorzolamide/timolol combination group versus 25.6 mmHg in the latanoprost group in Study 1, and 25.3 mmHg in the Dorzolamide/timolol combination group versus 24.7 mmHg in the latanoprost group in Study 2. After 3 months, the mean daytime diurnal IOP was 18.9 mmHg for the Dorzolamide/timolol combination versus 18.4 mmHg for latanoprost in Study 1, and 17.4 mmHg for the Dorzolamide/timolol combination versus 17.5 mmHg for latanoprost in Study 2. The difference between treatments in mean IOP change at 3 months was − 0.04 mmHg [95% confidence interval (CI) − 0.85, 0.77] in Study 1, and − 0.57 mmHg (95% CI − 1.31, 0.16) in Study 2. The probability that the true difference lay between − 1.5 and 1.5 mmHg, the predefined bounds for equivalance, was > 0.950 in both studies. Both treatments were well tolerated over 3 months, although ocular stinging occurred more frequently with the Dorzolamide/timolol combination. Conclusion: The Dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP.
-
The efficacy and safety of the Dorzolamide-timolol combination versus the concomitant administration of its components.
Ophthalmology, 1998Co-Authors: Kim M. Strohmaier, Ellen Snyder, Harvey Dubiner, Ingrid AdamsonsAbstract:Abstract Objective To evaluate whether a fixed combination of 2% Dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% Dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. Design Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. Participants and intervention In the masked phase, 242 patients received either the Dorzolamide-timolol combination twice daily and placebo three times daily or Dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the Dorzolamide-timolol combination twice daily for up to 9 months. Main outcome measures The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. Results During 3 months of treatment, the Dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with Dorzolamide and timolol was approximately 16% at hour 0, 20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. Conclusions The IOP-lowering effect of the Dorzolamide-timolol combination is comparable to that of Dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The Dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.
-
The efficacy and safety of the Dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group.
Ophthalmology, 1998Co-Authors: Kim M. Strohmaier, Ellen Snyder, Harvey Dubiner, Ingrid AdamsonsAbstract:OBJECTIVE To evaluate whether a fixed combination of 2% Dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% Dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. DESIGN Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. PARTICIPANTS AND INTERVENTION In the masked phase, 242 patients received either the Dorzolamide-timolol combination twice daily and placebo three times daily or Dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the Dorzolamide-timolol combination twice daily for up to 9 months. MAIN OUTCOME MEASURES The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. RESULTS During 3 months of treatment, the Dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with Dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. CONCLUSIONS The IOP-lowering effect of the Dorzolamide-timolol combination is comparable to that of Dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The Dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.
-
Two-year Safety Study of Dorzolamide as Monotherapy and With Timolol and Pilocarpine. Dorzolamide Safety Study Group
Journal of glaucoma, 1998Co-Authors: Ingrid Adamsons, Polis AAbstract:Purpose To evaluate the safety of open-label 2.0% Dorzolamide as monotherapy and when used with timolol and/or pilocarpine for as long as 2 years. Methods The safety of Dorzolamide was evaluated in patients with open-angle glaucoma or ocular hypertension over a 2-year period. The incidence of the most common drug-related adverse experiences in the first year was compared with that in the second year using McNemar's test. The ocular hypotensive effect of Dorzolamide as monotherapy and with adjunctive therapy was assessed using percent change in intraocular pressure (IOP) from baseline. Results Of the 304 patients enrolled, 164 (53.9%) continued to receive Dorzolamide as monotherapy for 2 years and 140 (46.1%) required add-on therapy. Add-on therapy was initiated by month 6 in 112 of these 140 patients (80%). Of the 304 patients, 202 (66.4%) completed 2 years of therapy. Of the patients who received Dorzolamide as monotherapy, drug-related adverse events occurred more frequently during the first year (29.7%) than the second year (13.8%), and the most common ocular drug-related adverse events included conjunctivitis, burning/stinging eye, follicular conjunctivitis, and eyelid edema. After 2 years of therapy, the mean percent decrease in peak IOP was 22.8% for patients receiving Dorzolamide monotherapy and 31.2% to 36.0% for patients receiving add-on therapy. Conclusion Dorzolamide was generally well tolerated for up to 2 years as mono-therapy and when used with timolol and/or pilocarpine. Drug-related adverse events were less frequent during the second year of monotherapy than during the first year. Most patients who required add-on therapy did so within the first 6 months of initiating Dorzolamide therapy.
Alon Harris - One of the best experts on this subject based on the ideXlab platform.
-
The Additive Effect of Dorzolamide Hydrochloride 2% to Bimatoprost 0,03% on Intraocular Pressure and Retrobulbar Blood Flow in Patients with Primary Open-Angle Glaucoma.
British Journal of Ophthalmology, 2010Co-Authors: Andrzej Stankiewicz, Joanna Wierzbowska, Anna Siemi¹tkowska, Beata Fuksiñska, Jacek Robaszkiewicz, Arkadiusz Zegad³o, Rita Ehrlich, Brent Siesky, Alon HarrisAbstract:Aims: To assess the additive effect of Dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retrobulbar hemodynamics in primary open-angle glaucoma (POAG) patients treated with morning-dosed bimatoprost 0.03%. Methods: Twenty five POAG patients, previously treated with any prostaglandin analogs, were evaluated in an prospective, single-masked study. After a week of run-in period with bimatoprost all patients were treated with bimatoprost dosed once in the morning for 1 month, after which Dorzolamide was added twice daily for 2 months. Goldmann applanation IOP, arterial blood pressure (ABP) and heart rate were measured every 2 hours for 24 hours and diurnal ocular perfusion pressure (OPP) was calculated. Color Doppler Imaging (CDI) of the ophthalmic (OA) and central retinal arteries (CRA) was recorded five times daily. All measurements were taken after two phases of treatment and compared. Results.The mean baseline IOP was 14.8 ± 3.5 mmHg. Mean IOP, following bimatoprost monotherapy (12.8 ± 2.9 mmHg) and after two months of Dorzolamide adjunctive therapy (12.2 ± 2.6 mmHg) were not statistically significant (p=0.544). Only at the 4 AM timepoint IOP was significantly reduced using the bimatoprost/Dorzolamide combined therapy (p=0.013). The 24-hour IOP fluctuations were lower when Dorzolamide was added (6.0 ± 2.3 mmHg vs. 4.6 ± 1.5 mmHg, p=0.0016). Repeated ANOVA analysis detected a significant decrease of vascular resistance in the OA(p=0.0167) with adjunctive Dorzolamide treatment. Conclusions.The addition of Dorzolamide to morning-dosed bimatoprost had an additive hypotensive effect only on the nighttime IOP curve at 4 AM and resulted in a lower IOP fluctuation. Dorzolamide added to bimatoprost may reduce vascular resistance in the OA.
-
Effects of topical Dorzolamide on retinal and retrobulbar hemodynamics
Acta ophthalmologica Scandinavica, 2009Co-Authors: Alon Harris, O Arend, Suzanne Arend, Bruce J MartinAbstract:. Purpose: Topical carbonic anhydrase inhibitors such as Dorzolamide have been developed as ocular hypotensive agents devoid of the side effects plaguing their systemic predecessors. We evaluated the influence of Dorzolamide on retinal and retrobulbar blood flow markers to determine if the drug has orbital vascular as well as ocular hypotensive effects. Methods: Eleven persons with healthy eyes received either placebo or two drops 2% Dorzolamide, 2 h prior to studies conducted in double-masked, counterbalanced fashion. Four retrobulbar vessels (nasal and temporal posterior ciliary, central retinal, and ophthalmic arteries) were analyzed by color Doppler imaging; scanning laser ophthalmoscopy was used to examine retinal and superficial optic nerve head blood linear velocity. Results: Dorzolamide lowered IOP from 15.7 ± 0.7 to 13.7 ± 0.7 mmHg (p < 0.05). The drug also hastened retinal arteriovenous passage of fluorescein dye, and accelerated capillary dye transit in the macula and optic nerve head. The drug, however, left unaltered blood velocity or resistance index in any retrobulbar vessel. Conclusions: Dorzolamide is an effective ocular hypotensive agent that accelerates blood velocity in the retinal and superficial optic nerve head without an apparent effect upon retrobulbar hemodynamics.
-
Dorzolamide-Timolol Combination and Retinal Vessel Oxygen Saturation in Patients with Glaucoma or Ocular Hypertension
The British journal of ophthalmology, 2009Co-Authors: Sindri Traustason, Einar Stefánsson, Thor Eysteinsson, Sveinn Hakon Hardarson, Maria Soffia Gottfredsdottir, Robert Arnar Karlsson, Alon HarrisAbstract:Aims: To examine whether the addition of Dorzolamide to timolol monotherapy influences oxygen saturation in the human retina. Methods: Non-invasive spectrophotometric retinal oximetry was used to measure oxygen saturation in retinal vessels. Twenty patients with open-angle glaucoma (11) and ocular hypertension (9) were recruited. The patients were randomised into receiving timolol monotherapy or Dorzolamide–timolol combination for an 8-month test period, followed by a second test period, before which the patients switched treatments. Oximetry measurements were performed at 2-month intervals during each period. Of the 20 patients, 13 followed the study protocol into the second test period, and 10 managed all study visits. Results: The oxygen saturation in retinal vessels was stable within the test periods. The mean arteriolar saturation was 96 (2)% (mean (SD)) during timolol monotherapy and 97 (2)% during Dorzolamide–timolol combination therapy (p = 0.17, all patients pooled, n = 13). Corresponding values in venules were 66 (5)% during timolol monotherapy and 65 (6)% during Dorzolamide–timolol therapy (p = 0.13). Patients who started on Dorzolamide–timolol combination showed a significant reduction in arteriolar (98 (2)% to 95 (2)%, p Conclusion: Adding Dorzolamide to timolol monotherapy has a minimal effect, but going from Dorzolamide–timolol combination to timolol alone lowered arteriolar and venular oxygen saturation. The retinal oxygen saturation measurements show a high degree of stability over an extended period of time. Previous studies have suggested increased retinal and optic nerve blood flow with Dorzolamide. Unchanged oxygen saturation and increased blood flow would indicate increased oxygen delivery to the retina.
-
a comparative study of betaxolol and Dorzolamide effect on ocular circulation in normal tension glaucoma patients
Ophthalmology, 2000Co-Authors: Alon Harris, O Arend, Hak Sung Chung, Larry Kagemann, Louis B Cantor, Bruce J MartinAbstract:Abstract Objective To determine whether dosages of a selective β-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (Dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation. Design Counterbalanced crossover, with open-label use of medications. Participants Nine persons with normal-tension glaucoma (NTG). Intervention After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either Dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics. Main outcome measures At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging. Results Betaxolol and Dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P P Conclusions Although both Dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, Dorzolamide alone accelerates inferotemporal retinal dye transit.
William C. Stewart - One of the best experts on this subject based on the ideXlab platform.
-
24 hour intraocular pressures with brimonidine purite versus Dorzolamide added to latanoprost in primary open angle glaucoma subjects
Ophthalmology, 2005Co-Authors: Anastasios G P Konstas, Costas H Karabatsas, Nikolaos Lallos, Nikolaos Georgiadis, Aikaterini Kotsimpou, Jeanette A Stewart, William C. StewartAbstract:OBJECTIVE: To evaluate the 24-hour efficacy of brimonidine purite versus Dorzolamide, each added to latanoprost. DESIGN: Double-masked, 2-center, prospective, crossover comparison. PARTICIPANTS: Primary open-angle glaucoma (POAG) subjects. METHODS: Subjects were randomized to brimonidine purite or Dorzolamide, each given twice daily, for the first 6-week treatment period after a 6-week latanoprost run-in. Subjects began the opposite treatment for the second 6-week period after a 6-week latanoprost-only treatment between periods. Intraocular pressure (IOP) was measured at 8 am, 12 pm, 4 pm, 8 pm, 12 am, 4 am, and 8 am at each baseline and at the end of each treatment period. This study provided an 80% power that a 1.5-mmHg difference could be excluded between groups if 27 subjects completed the study. A standard deviation (SD) of 2.8 mmHg was assumed. MAIN OUTCOME MEASURES: Twenty-four-hour efficacy of intraocular pressures of brimonidine purite versus Dorzolamide, each added to latanoprost. RESULTS: In 31 completed subjects, the baseline mean diurnal 24-hour IOP (+/- SD) was 19.0+/-1.7 mmHg for brimonidine purite and 19.0+/-1.6 mmHg for Dorzolamide (P = 0.52). The 8 am IOP after 6 weeks of therapy was 18.4+/-2.1 mmHg for brimonidine purite and 18.9+/-1.9 mmHg for Dorzolamide (P = 0.40). The mean diurnal IOP was 16.9+/-1.5 mmHg for brimonidine purite and 16.8+/-1.5 mmHg for Dorzolamide (P = 0.66). Dorzolamide caused a more bitter taste (P = 0.01) than brimonidine purite. CONCLUSIONS: This study suggests that brimonidine purite and Dorzolamide, added to latanoprost, have similar efficacy and safety in POAG or ocular hypertensive subjects.
-
Tolerability and efficacy of Dorzolamide versus acetazolamide added to timolol.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2002Co-Authors: William C. Stewart, Lee K. Halper, Lisa Johnson-pratt, Adam B. Polis, David HartenbaumAbstract:Purpose: Evaluate the safety and efficacy of Dorzolamide versus acetazolamide when added to once daily 0.5% timolol maleate ophthalmic gel forming solution (timolol gel). Methods: This was a randomized, double-masked, multicenter, active-controlled, parallel group study of 215 patients with open-angle glaucoma or ocular hypertension. Following a two-week treatment period with timolol gel, patients with IOP ≥ 22 mm Hg and who tolerated one week of acetazolamide 250-mg q.i.d. either were randomized to acetazolamide or Dorzolamide 2% three times daily for 12 weeks. Results: In 155 randomized patients (Dorzolamide, N = 80, acetazolamide, N = 75), compared to the Dorzolamide, acetazolamide had a statistically greater number of systemic adverse events (Dorzolamide 50%, acetazolamide 75%, p = 0.001), adverse events associated with carbonic anhydrase inhibitor (CAI) therapy (Dorzolamide 26%, acetazolamide 53%, p < 0.001) and discontinuations due to CAI adverse experiences (Dorzolamide 8%, acetazolamide 24%, p = 0...
-
brimonidine 0 2 versus Dorzolamide 2 each given three times daily to reduce intraocular pressure
American Journal of Ophthalmology, 2000Co-Authors: William C. Stewart, Elizabeth D Sharpe, Thomas S Harbin, Scott Pastor, Douglas G Day, Keri T Holmes, Jeanette A StewartAbstract:Abstract PURPOSE: To evaluate the efficacy and safety of brimonidine compared with Dorzolamide given three times daily as monotherapy in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In a double-masked, multicenter, crossover comparison in 40 patients, qualified patients were washed out from their previous medication and randomized to Dorzolamide 2% or brimonidine 0.2% for the first 6-week treatment period. Patients then were washed out for 2 weeks and started on the opposite medication for the second 6-week period. RESULTS: Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 ± 2.0 mm Hg. This study found that the 8:00 am trough intraocular pressure after 6 weeks of therapy for Dorzolamide was 20.7 ± 3.1 mm Hg and for brimonidine 20.8 ± 3.2 mm Hg ( P = .99). The peak intraocular pressure (2 hours after dosing) for Dorzolamide was 18.6 ± 3.4 mm Hg and for brimonidine 17.8 ± 2.7 mm Hg ( P = .10 ). Dorzolamide caused more stinging upon instillation ( P P = .01). No statistical differences existed between groups for systemic adverse events. Six patients, all on brimonidine, were discontinued from a treatment period early. Of these, two were discontinued for inadequate pressure control, two with dizziness and fatigue, one with ocular pain, and one for lifestyle reasons ( P = .07). CONCLUSIONS: This study found similar efficacy and safety between monotherapy treatment with Dorzolamide or brimonidine when each was given three times daily to patients with ocular hypertension or primary open-angle glaucoma.
Bruce M Shields - One of the best experts on this subject based on the ideXlab platform.
-
a comparison of Dorzolamide timolol combination versus the concomitant drugs
American Journal of Ophthalmology, 2000Co-Authors: Saira Choudhri, Martin Wand, Bruce M ShieldsAbstract:Abstract PURPOSE: To compare the intraocular pressure (IOP) lowering effect of fixed combination Dorzolamide 2% and timolol 0.5% therapy to that of concomitant administration of a topical beta-blocker and Dorzolamide. METHODS: Seventy-four consecutive glaucoma patients were changed from a regimen including a topical beta-blocker and Dorzolamide to the fixed combination Dorzolamide–timolol in 1 eye, with the other eye used as the control. The average IOP readings before and 1 month after the change were compared. RESULTS: The mean baseline IOP in the entire study population was 19.4 ± 4.2 mm Hg in the study eyes and 16.9 ± 4.2 mm Hg in the control eyes. Four weeks after the medication change, the mean IOP was 17.3 ± 3.9 mm Hg in the study eyes ( P P = .02). The difference between the mean IOP change of 2.1 mm Hg in the study eyes and 0.8 mm Hg in the control eyes was found to be statistically significant ( P = .01). CONCLUSION: These findings suggest that the fixed combination Dorzolamide–timolol therapy achieves additional lowering of the intraocular pressure compared with the concomitant administration of a beta-blocker and Dorzolamide.
-
four week safety and efficacy study of Dorzolamide a novel active topical carbonic anhydrase inhibitor
Archives of Ophthalmology, 1993Co-Authors: Mark Wilkerson, Marshall N Cyrlin, Erik A Lippa, Donna Esposito, Denise Deasy, Deborrah Panebianco, Roselyn Fazio, Michael E Yablonski, Bruce M ShieldsAbstract:Objective: To investigate the activity and local and systemic safety of the topical carbonic anhydrase inhibitor, Dorzolamide hydrochloride. Design: Four-week, double-masked, randomized, placebo-5controlled, parallel, three-center study. Setting: Referral centers. Patients: Forty-eight patients with bilateral open angle glaucoma or ocular hypertension and intraocular pressure (IOP) greater than 22 mm Hg entered the study. Two of 28 patients receiving Dorzolamide and two of 20 patients receiving placebo were withdrawn due to adverse experiences. Intervention: Dorzolamide (2%) or placebo to each eye three times daily for 4 weeks. Main Outcome Measures: Diurnal IOP curves; ophthalmologic evaluations including corneal ultrasound pachymetry and endothelial cell count; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug and carbonic anhydrase activity levels in red blood cells. Results: Mean IOP at morning trough (8am) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with Dorzolamide (−13.3%) compared with a decrease from 27.1 mm Hg to 26.4 mm Hg with placebo (−2.3%). Peak activity occurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with Dorzolamide (−18.4%) vs 26.1 mm Hg to 25.5 (−2.4%) with placebo. Mean corneal thickness was slightly increased for the Dorzolamide-treated group compared with the placebo-treated group (0.009 mm vs 0.001 mm, respectively, P 2 vs −27 cells/mm 2 , respectively, P >.25). Mean carbonic anhydrase isoenzyme II activity in red blood cells decreased to 21% of baseline in Dorzolamide-treated patients. There were no clinically significant differences in ocular or laboratory parameters between the Dorzolamide and placebo groups. Conclusions: Dorzolamide demonstrated significant IOP lowering activity over 4 weeks. It was well tolerated and there were no clinically significant changes in ocular or systemic safety parameters.
Douglas Ormrod - One of the best experts on this subject based on the ideXlab platform.
-
Topical Dorzolamide 2%/Timolol 0.5%
Drugs & Aging, 2000Co-Authors: Douglas Ormrod, Karen McclellanAbstract:The nonselective β-blocker timolol and the carbonic anhydrase inhibitor dorzol-amide both lower intraocular pressure (IOP). Timolol and Dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and Dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that Dorzolamide 2%/timolol 0.5% (Dorzolamide/timolol) is superior to monotherapy with the individual components. When Dorzolamide/timolol administered twice daily was compared with concomitant treatment with Dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included Dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the Dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, Dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug. Conclusions : Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line mono-therapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, Dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness. Pharmacodynamic Properties Dorzolamide is a sulfonamide and a carbonic anhydrase (CA) inhibitor while timolol is a nonselective β-blocker. As there is no direct interaction between the 2 drugs, their pharmacodynamics will be considered independently. Timolol is a nonselective β-blocker which has no local anaesthetic, membrane stabilising or sympathomimetic properties. However, the precise mechanism by which timolol lowers intraocular pressure (IOP) is not known. Timolol lowers IOP by inhibiting aqueous humour production rather than by increasing outflow of aqueous humour and it has been suggested that timolol down-regulates adenylate cyclase by inhibiting β_2-adrenoceptor sites at the ciliary process. Dose-response studies in volunteers showed that timolol 0.5 to 1.5% significantly reduced IOP by up to 28% 2 to 5 hours after drug administration. Topically instilled timolol is absorbed systemically and statistically significant decreases in resting heart rate have been reported after a year or more of treatment with timolol. Slight decreases in blood pressure have also been noted. Dorzolamide is a highly selective inhibitor of CA-II, an isoenzyme present on the ciliary process in the eye. Inhibition of CA-II slows local bicarbonate production, decreases sodium and fluid transport and, consequently, decreases aqueous humour production and lowers IOP. Reduction of IOP has been demonstrated after topical administration of Dorzolamide to the eyes of healthy volunteers and patients with open-angle glaucoma or ocular hypertension. Topically applied Dorzolamide can enter the systemic circulation: CA-II activity in erythrocytes of patients with glaucoma was reduced to 12% of baseline after treatment with Dorzolamide 2% for 12 months. However, research suggests that
-
Topical Dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open-angle glaucoma.
Drugs & aging, 2000Co-Authors: Douglas Ormrod, Karen J. McclellanAbstract:Abstract The nonselective β-blocker timolol and the carbonic anhydrase inhibitor dorzol-amide both lower intraocular pressure (IOP). Timolol and Dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and Dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that Dorzolamide 2%/timolol 0.5% (Dorzolamide/timolol) is superior to monotherapy with the individual components. When Dorzolamide/timolol administered twice daily was compared with concomitant treatment with Dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included Dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the Dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, Dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug. Conclusions: Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line mono-therapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, Dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness.