Clinical Experience with Timolol and Brinzolamide Fixed-combination: A Case Series

One of the approaches to improve the adherence of patients with primary open-angle glaucoma (POAG) to IOP-lowering eye drops therapy is the use of fixed-combinations (FC), since this makes it possible to reduce treatment cost during combined therapy, reduce the number of instillations per day, minimize the risk of “missing” instillations and reduce the effect of the eye drops preservative on the ocular surface. Increasing patient compliance may also be associated with the use of generics that have pharmacological and therapeutic equivalence to original drugs at a lower cost. The article presents the clinical cases generic 1.0 % brinzolamide + 0.5 % timolol FC instillations in POAG patients. The 1^st-clinical case demonstrates comparable efficacy and safety of the generic brinzolamide + timolol FC, compared with the original medication, which is confirmed by the data of a number of authors (A.V. Sidorova et al., 2023), and allows us to talk about the possibility of patients transition from the original to the reproduced eye drops to minimize the cost of therapy. The 2^nd-clinical case illustrates the possibility and effectiveness of starting with combined IOP-lowering therapy (based on generic brinzolamide + timolol FC instillation) at the II-stage of POAG with high IOP level, as well as at the III-stage of POAG with an extremely high initial IOP level (brinzolamide + timolol FC and 0.03 % bimatoprost instillations). The 3^rd-clinical case shows that generic timolol + brinzolamide FC can be effectively used during maximum-IOP-lowering therapy in combination with prostaglandin and brimonidine.

1. Neroev VV, Egorov EA, Moshetova LK. Ophthalmology. National guide. Moscow: GEOTAR‑Media; 2025 (In Russ.).

2. National guidelines for glaucoma for practitioners. Ed. 4th, corrected and supplemented. Ed. by Egorov EA, Erichev VP. Moscow: GEOTAR‑Media, 2019. 384 p. (In Russ.).

3. Terminology and guidelines for glaucoma. 5th edition. EGS. 2020. 168 p.

4. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open‑angle glaucoma. Arch Ophthalmol. 2002 Jun;120(6):701–713; discussion 829–830. doi: 10.1001/archopht.120.6.701.

5. Makogon SI, Onishchenko AL, Yatsenko LL, Karmanova OA. Efficacy of first‑choice therapy in the treatment of newly diagnosed primary glaucoma. Natsional’nyi zhurnal glaukoma. 2018;17(2):28–37 (In Russ.).

6. Onishchenko AL, Isakov IN, Kolbasko AV. Initial combination therapy for primary open‑angle glaucoma. Russian Annals of Ophthalmology. 2019:135(2):32–38 (In Russ.). doi: 10.17116/oftalma201913502132.

7. Olthoff CM, Schouten JS, van de Borne BW, Webers CA. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidencebased review. Ophthalmology. 2005 Jun;112(6):953–961. doi: 10.1016/j.ophtha.2004.12.035.

8. Hoevenaars JGMM, Schouten JSAG, Van Den Borne Will improvement of knowledge lead to improvement of compliance with glaucoma medication? Acta Ophthalmologica. 2008:86:849–855. doi: 10.1111/j.1755‑3768.2007.01161.x.

9. Zaharia AC, Dumitrescu OM, Radu M. Adherence to Therapy in Glaucoma Treatment — A Review. J Pers Med. 2022:12(4):514. doi: 10.3390/jpm12040514.

10. Traverso CE, Walt JG, Kelly SP. Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe. Br J Ophthalmol. 2005:89(10):1245–1249. doi: 10.1136/bjo.2005.067355.

11. Fiscella RG, Lee J, Davis EJ, Walt J. Cost of illness of glaucoma: a critical and systematic review. Pharmacoeconomics. 2009:27(3):189–198. doi: 10.2165/00019053200927030‑00002.

12. Kahook MY, Noecker R. Quantitative analysis of conjunctival goblet cells after chronic application of topical drops. Adv Ther. 2008:25(8):743–751. doi: 10.1007/s12325‑008‑0078‑y.

13. Erb C. Glaucoma and Dry Eye. Bremen: UNI‑MED Verlag AG, 2012. 102 p.

14. Brzhesky VV, Egorova GV, Egorov EA. Dry eye and ocular surface diseases. Moscow: GEOTAR‑Media, 2016. 448 p. (In Russ.).

15. Brzhesky VV. Glaucoma and dry eye syndrome. Moscow: Borges, 2018. 228 p. (In Russ.).

16. Li G, Akpek EK, Ahmad S. Glaucoma and Ocular Surface Disease: More than Meets the Eye. Clin Ophthalmol. 2022:4(16):3641–3649. doi: 10.2147/OPTH.S388886.

17. Yanchenko SV, Malyshev AV, Sakhnov SN. Effectiveness and Safety of Cataract Surgery Pharmacological Support in Glaucoma Patients. Ophthalmology in Russia. 2018:15(3):330–338. (In Russ). doi: 10.18008/1816‑5095‑2018‑3‑330‑338.

18. Sakhnov SN, Yanchenko SV, Malyshev AV, Dashina VV, Ceeva AR, Petrosyan LM. Dry eye epidemiology in patients before cataract surgery. Ophthalmology in Russia 2020:17(2):281–289 (In Russ.). doi: 10/18008/1816‑5095‑2020‑2‑281‑289.

19. Yanchenko SV, Malyshev AV, Teshaev ShZh. Possibilities of Preservative‑Free Therapy for Primary Open‑Angle Glaucoma. Ophthalmology in Russia. 2023:20(4):780– 786 (In Russ.). doi: 10.18008/1816‑5095‑2023‑4‑780–786.

20. Sinha S, Lee D, Kolomeyer NN. Fixed combination netarsudil‑latanoprost for the treatment of glaucoma and ocular hypertension. Expert Opin Pharmacother. 2020:21(1):39–45. doi: 10.1080/14656566.2019.1685499.

21. Shirai C, Matsuoka N, Nakazawa T. Comparison of adherence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: a retrospective non‑interventional cohort study. BMC Ophthalmol. 2021:21(1):52. doi: 10.1186/s12886‑021‑01813‑w.

22. Popovic M, Chan C, Lattanzio N. Comparative cost evaluation of brand name and generic ophthalmology medications in Ontario. Can J Ophthalmol. 2018:53(2):173– 187. doi: 10.1016/j.jcjo.2017.08.003.

23. Malvankar‑Mehta MS, Feng L, Hutnik CM. North American cost analysis of brand name versus generic drugs for the treatment of glaucoma. Clinicoecon Outcomes Res. 2019:11:789‑798. doi: 10.2147/CEOR.S156558.

24. Antonov AA, Vitkov AA, Agadzhanyan TM. The efficacy and safety of the domestic travoprost generic in various modes of therapy for primary open‑angle glaucoma. National Journal of Glaucoma. 2021;20(4):50–56 (In Russ). doi: 10.53432/20784104‑2021‑20‑4‑50‑56.

25. Holló G, Bozkurt B, Irkec M. Brinzolamide/timolol fixed combination: a new ocular suspension for the treatment of open‑angle glaucoma and ocular hypertension. Expert Opin Pharmacother. 2009:10(12):2015–2024. doi: 10.1517/14656560903124388.

26. Inatani M, Orii Y, Iwasaki K. Randomized Multicenter Clinical Trial Comparing 0.1 % Brimonidine/0.5 % Timolol Versus 1 % Dorzolamide/0.5 % Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study. Adv Ther. 2023:40(9):4074–4092. doi: 10.1007/s12325‑023‑02589‑9.

27. Sidorova AV, Starostina AV, Burlakov KS. Evaluation of the efficacy and tolerability of 1 % brinzolamide and 0.5 % timolol fixed combination in the treatment of primary open‑angle glaucoma. Natsional’nyi zhurnal glaukoma. 2023;22(1):85–91 (In Russ.).

28. Januleviciene I. Brinzolamide 1 %/timolol 0.5 %: safety and efficacy of a new fixed‑combination IOP‑lowering product for glaucoma. Curr Med Res Opin. 2010:26(11):2575–2578. doi: 10.1185/03007995.2010.517718.

29. Doherty M, Fraser S, Phelan P. Brinzolamide‑timolol suspension: acceptability and side effect profile. Clin Ophthalmol. 2011:5:419–423. doi: 10.2147/OPTH.S18251.

30. Abisheva LD, Avdeev RV, Alexandrov AS. Optimal characteristics of the upper limit of ophthalmotonus in patients with advanced stage of primary open‑angle glaucoma in terms of evidence‑based medicine. Clinical ophthalmology. 2015:3:111–123 (In Russ.).

31. Egorov EA, Erichev VP, Kuroedov AV. Indicators of ophthalmotonometry in a healthy population. National Journal of Glaucoma. 2018:17(2):91–98 (In Russ).

32. Primary open‑angle glaucoma. Clinical guidelines of the Russian Federation. 2024. 68 p. (In Russ.).

33. Craig JP, Nelson JD, Azar DT. TFOS DEWS II Report Executive Summary. The Ocular Surface. 2017:15:1–11. doi: 10.1016/j.jtos.2017.08.003.