Фиксированная комбинация бринзоламида и бримонидина в терапии открытоугольной глаукомы и офтальмогипертензии: обзор гипотензивной эффективности и переносимости

Проанализированы данные 12-летнего клинического применения фиксированной комбинации 1 % бринзоламида и 0,2 % бримонидина (ФКББ) в терапии глаукомы и офтальмогипертензии. Данный лекарственный препарат является альтернативой для пациентов с системными противопоказаниями в виде бронхообструктивного синдрома и сердечно-сосудистой патологии. Гипотензивный эффект ФКББ в качестве монотерапии, согласно данным литературы, достигает 30 % от исходного офтальмотонуса и соответствует таковому при нефиксированной комбинированной терапии входящими в состав ФКББ препаратами. Переключение пациентов с глаукомой и офтальмогипертензией с монотерапии бринзоламидом или бримонидином на ФКББ сопровождается добавочным гипотензивным эффектом на уровне 13 % от исходного внутриглазного давления. Препарат ФКББ обладает хорошим добавочным гипотензивным эффектом в комбинации с препаратами других фармацевтических групп, а также эффективно купирует гипертензионный симптом после ряда офтальмохирургических вмешательств, таких как лазерная капсулотомия при вторичной катаракте, интравитреальное введение анти-VEGF препаратов и факоэмульсификация катаракты. В качестве наиболее частых офтальмологических нежелательных явлений при применении ФКББ отмечены конъюнктивальная гиперемия, конъюнктивит, аллергические реакции и дискомфорт в глазах с частотой порядка 10–20 %.

1. European Glaucoma Society. Terminology and guidelines for glaucoma. 5th edition ed: Savona, Italy PubliComm; 2020.

2. Клинические рекомендации «Глаукома первичная открытоугольная» ID 96_2 (17.08.2024),

3. Friedman DS, Nordstrom B, Mozaffari E, Quigley HA. Glaucoma management among individuals enrolled in a single comprehensive insurance plan. Ophthalmology. 2005; 112 (9): 1500–4. doi: 10.1016/j.ophtha.2005.02.030

4. Higginbotham EJ. Ocular Hypertension Treatment Study. Arch Ophthalmol. 2009; 127 (2): 213–5. doi: 10.1001/archophthalmol.2008.599

5. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001; 108 (11): 1943–53. doi: 10.1016/s0161-6420(01)00873-9

6. Корнеева А.В., Куроедов А.В., Завадский П.Ч. и др. Приверженность гипотензивной терапии при глаукоме: мнение пациентов о ключевых факторах низкой степени комплаенса. Результаты многоцентрового интерактивного научно-аналитического исследования. Национальный журнал глаукома. 2020; 19 (3): 12–21. doi: 10.25700/NJG.2020.03.02

7. Barnebey HS, Robin AL. Adherence to fixed-combination versus unfixed Travoprost 0.004 %/Timolol 0.5 % for glaucoma or ocular hypertension: A randomized trial. Am J Ophthalmol. 2017; 176: 61–9. doi: 10.1016/j.ajo.2016.12.002

8. Gedde SJ, Vinod K, Wright MM, et al. Primary Open-Angle Glaucoma Preferred Practice Pattern(R). Ophthalmology. 2021; 128 (1): P71–P150. doi: 10.1016/j.ophtha.2020.10.022

9. Konstas AG, Schmetterer L, Costa VP, et al. Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review. Expert Opin Drug Saf. 2020; 19 (11): 1445–60. doi: 10.1080/14740338.2020.1826928

10. Poleon S, Twa M, Schoenberger-Godwin YM, Fifolt M, Racette L. A Taxonomy of behavior change techniques for improving medication adherence in primary open-angle glaucoma. J Ophthalmol. 2025; 2025: 9917724. doi: 10.1155/joph/9917724

11. Higginbotham EJ, Hansen J, Davis EJ, Walt JG, Guckian A. Glaucoma medication persistence with a fixed combination versus multiple bottles. Curr Med Res Opin. 2009; 25 (10): 2543–7. doi: 10.1185/03007990903260129

12. Журавлева А.Н., Зуева М.В., Шустов Е.Б. Оптимизация медикаментозного лечения больных глаукомой при сочетании с сопутствующей системной патологией. Часть 1: сердечно-сосудистая патология. Офтальмология. 2020; 17 (3): 321–9. doi: 10.18008/1816-5095-2020-3-321-329

13. Taniguchi T, Kitazawa Y. The potential systemic effect of topically applied beta-blockers in glaucoma therapy. Curr Opin Ophthalmol. 1997; 8 (2): 55–8. doi: 10.1097/00055735-199704000-00010

14. Инструкция по медицинскому применению препарата «Тимолол-СОЛОфарм». URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=e879f1bb-52a5-4917-9e11-2cb8cde1e56e (дата обращения: 19.08.2023).

15. Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidencebased assessment. Am J Ophthalmol. 2002; 134 (5): 749–60. doi: 10.1016/s0002-9394(02)01699-9

16. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Arch Ophthalmol. 1984; 102 (4): 551–3. doi: 10.1001/archopht.1984.01040030429017

17. Williamson J, Young JD, Atta H, Muir G, Kadom H. Comparative efficacy of orally and topically administered beta blockers for chronic simple glaucoma. Br J Ophthalmol. 1985; 69 (1): 41–5. doi: 10.1136/bjo.69.1.41

18. Simbrinza (brinzolamide/brimonidine tartrate ophthalmic suspension) 1 %/0.2 % [package insert]. Fort Worth, TX: Alcon Laboratories Inc; 2013.

19. Усман А.Б., Марченко Л.Н., Джумова М.Ф., Далидович А.А. Применение фиксированной комбинации бримонидин тартрата и бринзоламида в лечении начальной стадии первичной открытоугольной глаукомы. Медицинский журнал. 2018; 2: 118–21.

20. Dong CJ, Guo Y, Agey P, Wheeler L, Hare WA. Alpha2 adrenergic modulation of NMDA receptor function as a major mechanism of RGC protection in experimental glaucoma and retinal excitotoxicity. Invest Ophthalmol Vis Sci. 2008; 49 (10): 4515–22. doi: 10.1167/iovs.08-2078

21. Hernandez M, Urcola JH, Vecino E. Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments. Exp Eye Res. 2008; 86 (5): 798–806. doi: 10.1016/j.exer.2008.02.008

22. Lambert WS, Ruiz L, Crish SD, Wheeler LA, Calkins DJ. Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons. Mol Neurodegener. 2011; 6 (1): 4. doi: 10.1186/1750-1326-6-4

23. Suzuki G, Kunikane E, Shigemi W, et al. Ocular and systemic pharmacokinetics of brimonidine and brinzolamide after topical administration in rabbits: comparison between fixed-combination and single-drug formulations. Curr Eye Res. 2021; 46 (3): 380–6. doi: 10.1080/02713683.2020.1800046

24. Nguyen QH, McMenemy MG, Realini T, Whitson JT, Goode SM. Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixedcombination brinzolamide 1 %/brimonidine 0.2 %. J Ocul Pharmacol Ther. 2013; 29 (3): 290–7. doi: 10.1089/jop.2012.0235

25. Katz G, Dubiner H, Samples J, Vold S, Sall K. Three-month randomized trial of fixed-combination brinzolamide, 1 %, and brimonidine, 0.2 %. JAMA Ophthalmol. 2013; 131 (6): 724–30. doi: 10.1001/jamaophthalmol.2013.188

26. Realini T, Nguyen QH, Katz G, DuBiner H. Fixed-combination brinzolamide 1 %/brimonidine 0.2 % vs monotherapy with brinzolamide or brimonidine in patients with open-angle glaucoma or ocular hypertension: results of a pooled analysis of two phase 3 studies. Eye (Lond). 2013; 27 (7): 841–7. doi: 10.1038/eye.2013.83

27. Aung T, Laganovska G, Hernandez Paredes TJ, et al. Twice-daily brinzolamide/ brimonidine fixed combination versus brinzolamide or brimonidine in openangle glaucoma or ocular hypertension. Ophthalmology. 2014; 121 (12): 2348–55. doi: 10.1016/j.ophtha.2014.06.022

28. Jin SW, Lee SM. The efficacy and safety of the fixed combination of brinzolamide 1 % and brimonidine 0.2 % in normal tension glaucoma: An 18-month retrospective study. J Ocul Pharmacol Ther. 2018; 34 (3): 274–9. doi: 10.1089/jop.2017.0075

29. Inoe K, Kunimatsu-Sanuki S, Ishida K, Tomita G. Intraocular pressurelowering effects and safety of brimonidine/brinzolamide fixed combination after switching from other medications. Jpn J Ophthalmol. 2022; 66 (5): 440–6. doi: 10.1007/s10384-022-00930-3

30. Gandolfi SA, Lim J, Sanseau AC, Parra Restrepo JC, Hamacher T. Randomized trial of brinzolamide/brimonidine versus brinzolamide plus brimonidine for open-angle glaucoma or ocular hypertension. Adv Ther. 2014; 31 (12): 1213–27. doi: 10.1007/s12325-014-0168-y

31. Moosavi R, Ansari E. Brinzolamide/Brimonidine fixed combination: Simplifying glaucoma treatment regimens. Ophthalmol Ther. 2018; 7 (2): 397–403. doi: 10.1007/s40123-018-0150-x

32. Wang N, Lu DW, Pan Y, et al. Comparison of the intraocular pressure-lowering efficacy and safety of the brinzolamide/brimonidine fixed-dose combination versus concomitant use of brinzolamide and brimonidine for management of open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2020; 14: 221–30. doi: 10.2147/OPTH.S231402

33. Onoe H, Hirooka K, Nagayama M, et al. The efficacy, safety and satisfaction associated with switching from brinzolamide 1 % and brimonidine 0.1 % to a fixed combination of brinzolamide 1% and brimonidine 0.1 % in glaucoma patients. J Clin Med. 2021 Nov; 10 (22): 5258. doi: 10.3390/jcm10225228

34. Onoe H, Hirooka K, Nagayama M, et al. The efficacy, safety, and satisfaction associated with switching from brinzolamide or brimonidine to brinzolamide/ brimonidine in open-angle glaucoma patients. J Pers Med. 2022 Dec; 12 (12): 2057. doi: 10.3390/jpm12122057

35. Aoki R, Terao E, Dote S, et al. Efficacy and safety of a fixed combination of 1 % brinzolamide and 0.1 % brimonidine as treatment for glaucoma: a retrospective study focusing on the number of ingredients. BMJ Open Ophthalmol. 2022 Dec; 7 (1): e001200. doi: 10.1136/bmjophth-2022-001200

36. Fechtner RD, Myers JS, Hubatsch DA, Budenz DL, DuBiner HB. Ocular hypotensive effect of fixed-combination brinzolamide/brimonidine adjunctive to a prostaglandin analog: a randomized clinical trial. Eye (Lond). 2016; 30 (10): 1343–50. doi: 10.1038/eye.2016.126

37. Topouzis F, Goldberg I, Bell K, et al. Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension. Eur J Ophthalmol. 2021; 31 (1): 103–11. doi: 10.1177/1120672119878044

38. Kozobolis V, Panos GD, Konstantinidis A, Labiris G. Comparison of dorzolamide/timolol vs brinzolamide/brimonidine fixed combination therapy in the management of primary open-angle glaucoma. Eur J Ophthalmol. 2017; 27 (2): 160–3. doi: 10.5301/ejo.5000826

39. Lo JS, Pang PM, Lo SC. Efficacy and tolerability of brinzolamide/brimonidine suspension and prostaglandin analogs in patients previously treated with dorzolamide/timolol solution and prostaglandin analogs. Clin Ophthalmol. 2016; 10: 583–6. doi: 10.2147/OPTH.S98607

40. Mishra A, Agrawal M, Tripathi A, et al. A comparative study on efficacy of intraocular pressure lowering of two fixed-dose antiglaucoma drug combination brinzolamide-brimonidine versus latanoprost-timolol in primary open-angle glaucoma and ocular hypertension. J Ocul Pharmacol Ther. 2024; 40 (4): 240–5. doi: 10.1089/jop.2023.0186

41. Seibold LK, DeWitt PE, Kroehl ME, Kahook MY. The 24-hour effects of brinzolamide/brimonidine fixed combination and timolol on intraocular pressure and ocular perfusion pressure. J Ocul Pharmacol Ther. 2017; 33 (3): 161–9. doi: 10.1089/jop.2016.0141

42. Weinreb RN, Bacharach J, Fechtner RD, et al. 24-hour intraocular pressure control with fixed-dose combination brinzolamide 1 % / brimonidine 0.2 %: A multicenter, randomized trial. Ophthalmology. 2019; 126 (8): 1095–104. doi: 10.1016/j.ophtha.2018.10.040

43. Feldman RM, Katz G, McMenemy M, Hubatsch DA, Realini T. A randomized trial of fixed-dose combination brinzolamide 1 % / brimonidine 0.2 % as adjunctive therapy to travoprost 0.004. Am J Ophthalmol. 2016 May; 165: 188–97. doi: 10.1016/j.ajo.2016.02.026

44. Lerner SF, Oddone F, Lu DW, et al. Maximum medical therapy: Brinzolamide/ Brimonidine and Travoprost/Timolol fixed-dose combinations in glaucoma and ocular hypertension. Clin Ophthalmol. 2019; 13: 2411–9. doi: 10.2147/OPTH.S228777

45. Tekeli O, Kose HC. Evaluation of the use of brinzolamide-brimonidine fixed combination in maximum medical therapy. Turk J Ophthalmol. 2022; 52 (4): 262–9. doi: 10.4274/tjo.galenos.2021.25488

46. Bakri SJ, Pulido JS, McCannel CA, et al. Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye (Lond). 2009; 23 (1): 181–5. doi: 10.1038/sj.eye.6702938

47. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006; 355 (14): 1432–44. doi: 10.1056/NEJMoa062655

48. Bunting HJ, Laganowski H. Routine follow-up after YAG laser capsulotomy for posterior capsule opacification. Eye (Lond). 2006; 20 (12): 1449–50. doi: 10.1038/sj.eye.6702315

49. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006; 355 (14): 1419–31. doi: 10.1056/NEJMoa054481

50. Stark WJ, Worthen D, Holladay JT, Murray G. Neodymium: YAG lasers. An FDA report. Ophthalmology. 1985; 92 (2): 209–12. doi: 10.1016/s0161-6420(85)34051-4

51. Aslam TM, Devlin H, Dhillon B. Use of Nd:YAG laser capsulotomy. Surv Ophthalmol. 2003; 48 (6): 594–612. doi: 10.1016/j.survophthal.2003.08.002

52. Ladas ID, Baltatzis S, Panagiotidis D, et al. Topical 2.0 % dorzolamide vs oral acetazolamide for prevention of intraocular pressure rise after neodymium:YAG laser posterior capsulotomy. Arch Ophthalmol. 1997; 115 (10): 1241–4. doi: 10.1001/archopht.1997.01100160411003

53. Oner V, Alakus MF, Tas M, Turkyilmaz K, Iscan Y. Fixed combination brimonidine-timolol versus brimonidine for treatment of intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy. J Ocul Pharmacol Ther. 2012; 28 (6): 576–80. doi: 10.1089/jop.2012.0092

54. Unal M, Yucel I, Akar Y. Brinzolamide 1 % versus apraclonidine 0.5 % to prevent intraocular pressure elevation after neodymium: YAG laser posterior capsulotomy. J Cataract Refract Surg. 2006; 32 (9): 1499–502. doi: 10.1016/j.jcrs.2006.04.014

55. Makri OE, Plotas P, Tsapardoni FN, Georgakopoulos CD. Brinzolamidebrimonidine fixed combination to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy. J Cataract Refract Surg. 2018; 44 (4): 514–5. doi: 10.1016/j.jcrs.2018.03.006

56. Dettoraki M, Rapti E, Fragkos D, et al. Prophylactic effect of brinzolamidebrimonidine fixed combination on intraocular pressure spikes after intravitreal anti-VEGF injections . Int Ophthalmol. 2021; 41 (9): 3191–8. doi: 10.1007/s10792-021-01885-z

57. Georgakopoulos CD, Kagkelaris K, Pagoulatos D, Plotas P, Makri OE. Brinzolamide-brimonidine fixed combination for the prevention of intraocular pressure elevation after phacoemulsification. Eur J Ophthalmol. 2020; 30 (2): 293–8. doi: 10.1177/1120672118817997

58. Takahashi N, Sato K, Kiyota N, et al. The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits. PLoS One. 2023; 18 (12): e0295122. doi: 10.1371/journal.pone.0295122

59. Whitson JT, Realini T, Nguyen QH, McMenemy MG, Goode SM. Sixmonth results from a phase III randomized trial of fixed-combination brinzolamide 1 % + brimonidine 0.2 % versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension. Clin Ophthalmol. 2013; 7: 1053–60. doi: 10.2147/OPTH.S46881

60. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS. 2001; 5 (5): 281–4. doi: 10.1067/mpa.2001.117571