An Open Label Prospective Randomized Trial to Compare The Efficacy Tolerability and Cost Effectiveness of Brand Name Versus Two Different Generic Drug of Fixed Combination Dorzolamide 2% and Timolol 0.5% in The Treatment of Primary Open Angle Glaucoma

Purpose: To compare the efficacy tolerability and cost effectiveness of brand name versus two different generic drug of fixed combination dorzolamide 2% and timolol 0.5% in the treatment of primary open angle glaucoma.Methods: Sixty-six eyes of 66 patients with newly diagnosed, open-angle glaucoma were included in this prospective, examiner masked, randomized study. All patients underwent routine ophthalmic examinations at baseline and 6 months of treatment. After initial examination, patients were randomly divided into three groups and prescribed to use fixed combination treatment of dorzolamide/timolol (D/T) brand name and two different generic name drops. Retrobulbar blood flow was assessed with color Doppler imaging (CDI). At end-of-treatment assessments, patients were requested to fill in a questionnaire based on "the Comparison of Ophthalmic Medications for Tolerability".Results: Intraocular pressure (IOP) and CDI measurements were similar at baseline. Compared to baseline, the brand name drop had a better resistive index lowering effect than two other generic drugs, however the difference was not statistically significant (p=0.056). Brand name D/T fixed combination provided greater significant mean IOP reductions from baseline than two other generic name drops (p=0.001). There were no statistically significant differences in the IOP lowering effect between generic drops (p=0.562). Tolerability was similar between groups. Generic bottles failed to last a month for 80% patients. Conclusions: Brand name product of D/T fixed combination is exactly more effective in IOP reduction and seems to be having a better lowering effect on resistive index, even a statistically significant result was not found.

Keywords:

generic drug, cost effectiveness, retrobulbar bloodflow color doppler imaging,

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1. Januleviciene I, Ehrlich R, Siesky B, Nedzelskiene I, Harris A. Visual function, optic nerve structure, and ocular blood flow parameters after 1 year of glaucoma treatment with fixed combinations. Eur J Ophthalmol 2009;19:790-797.2. Chen SD, Wang L, Zhang XL. Neuroprotection in glaucoma: present and future. Chin Med J 2013;126:1567-1577.3. Siesky B, Harris A, Ehrlich R, et al. Short-term effects of brimonidine/timolol and dorzolamide/timolol on ocular perfusion pressure and blood flow in glaucoma. Adv Ther 2012;29:53-63.4. Martinez A, Sanchez M. Effects of dorzolamide 2% added to timolol maleate 0.5% on intraocular pressure, retrobulbar blood flow, and the progression of visual field damage in patients with primary open-angle glaucoma: a single-center, 4-year, open-label study. Clin Ther 2008;30:1120-1134.5. Martinez A, Sanchez M. A comparison of the effects of 0.005% latanoprost and fixed combination dorzolamide/timolol on retrobulbar haemodynamics in previously untreated glaucoma patients. Curr Med Res Opin 2006;22:67-73.6. Harris A, Arend O, Kagemann L, Garrett M, Chung HS, Martin B. Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma. J Ocul Pharmacol Ther 1999;15:189-197.7. Martinez A, Sanchez-Salorio M. A comparison of the long-term effects of dorzolamide 2% and brinzolamide 1%, each added to timolol 0.5%, on retrobulbar hemodynamics and intraocular pressure in open-angle glaucoma patients. J Ocul Pharmacol Ther 2009;25:239-248.8. Martinez A, Sanchez-Salorio M. Predictors for visual field progression and the effects of treatment with dorzolamide 2% or brinzolamide 1% each added to timolol 0.5% in primary open-angle glaucoma. Acta Ophthalmol 2010;88:541-552.9. Fiscella RG, Jensen MK. Cost analysis of glaucoma medications. Am J Ophthalmol 2008;145:1108-1109; author reply 1109.10. Ikeda H, Tsukamoto H, Sawa A, Sugimoto A, Mishima H, Kihira K. Comparison of annual cost between brand and generic ocular beta-adrenergic blockers. Yakugaku Zasshi 2005;125:463-467.11. Schlenker MB, Trope GE, Buys YM. Comparison of United States and canadian glaucoma medication costs and price change from 2006 to 2013. J Ophthalmol 2015;2015:547960.12. Mehl B, Santell JP. Projecting future drug expenditures--2000. Am J Health Syst Pharm 2000;57:129-138.13. Barber BL, Strahlman ER, Laibovitz R, Guess HA, Reines SA. Validation of a questionnaire for comparing the tolerability of ophthalmic medications. Ophthalmol 1997;104:334-342.14. Beckers HJ, Schouten JS, Webers CA, van der Valk R, Hendrikse F. Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction. Graefe's Arch Clin Exp Ophthalmol 2008;246:1485-90.15. Alm A. Latanoprost in the treatment of glaucoma. Clin Ophthalmol 2014;8:1967-1985.16. Dubois VD. Are generic topical prostanoids the way forward in the care of glaucoma patients? - No. Eye 2013;27:1002-1003.17. Titcomb LC. Are generic topical prostanoids the way forward in the care of glaucoma patients? - Yes. Eye 2013;27:999-1001.18. Chambers WA. Ophthalmic generics--are they really the same? Ophthalmology 2012;119:1095-1096.19. Aref AA. Generic drugs for the treatment of ocular conditions: changing the treatment landscape. Expert Rew of Clin Pharmacol 2014;7:551-553.20. Mammo ZN, Flanagan JG, James DF, Trope GE. Generic versus brand-name North American topical glaucoma drops. Can J Ophthalmol 2012;47:55-61.21. Stewart WC, Sharpe ED, Stewart JA, Hott CE. The safety and efficacy of timolol 0.5% in xanthan gum versus timolol gel forming solution 0.5%. Curr Eye Res 2002;24:387-391.22. Narayanaswamy A, Neog A, Baskaran M, et al. A randomized, crossover, open label pilot study to evaluate the efficacy and safety of Xalatan in comparison with generic Latanoprost (Latoprost) in subjects with primary open angle glaucoma or ocular hypertension. Indian J Ophthalmol 2007;55:127-131.23. Egan P, Harris A, Siesky B, et al. Comparison of intraocular pressure in glaucoma subjects treated with Xalatan versus generic latanoprost. Acta Ophthalmol 2014;92:e415-416.24. Kim YI, Kim JH, Lee TY, Lee KW. Efficacy and Safety of Glaucoma Patients' Switch from a 2% Dorzolamide/0.5% Timolol Fixed-Combination Brand-Name Drug to Its Generic Counterpart. J Ocul Pharmacol Ther 2015;31:335-339.