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Travapress, 1 piece, 2.5 ml, 0.04 mg/ml, eye drops

Herbpress may cause a gradual change in eye color by increasing the number of melanosomes (pigment granules) in melanocytes. This effect is detected mainly in patients with mixed iris color, for example, blue-brown, gray-brown, green-brown or yellow-brown. This effect was also noted in patients with brown irises. Typically, brown pigmentation extends concentrically around the pupil to the periphery of the iris, and all or part of the iris may become a more intense brown color. The long-term effect on melanocytes and the consequences of this influence are currently unknown. Changes in iris color occur slowly and may go unnoticed for months or years. Before starting treatment, patients should be informed about the possibility of permanent changes in eye color. If only one eye is treated, persistent heterochromia may develop. After completion of travoprost therapy, no further increase in brown pigmentation of the iris was observed. Darkening of the skin of the eyelids and/or periorbital area has been reported in association with travoprost use in 0.4% of patients.

Travoprost may gradually change the structure of the eyelashes of the eye on which it is applied; During clinical studies, such changes were observed in approximately half of patients and included an increase in length, thickness, pigmentation and number of eyelashes. The mechanism of changes in the structure of eyelashes and the long-term consequences of this action are unknown today.

There is no experience with travoprost in inflammatory eye diseases, neovascular glaucoma, angle-closure glaucoma, narrow-angle or congenital glaucoma, and there is only limited experience in eye diseases caused by thyroid dysfunction, glaucoma in pseudophakic patients, pigmentary or pseudoexfoliative glaucoma.

It is recommended to prescribe Travapress with caution to patients with aphakia, pseudophakia, rupture of the posterior capsule of the lens, and with risk factors for the development of cystoid macular edema.

Contact of travoprost with skin should be avoided as studies in rabbits have shown transdermal absorption of travoprost.

Travapress should be prescribed with caution to patients with risk factors for developing iritis/uveitis.

Prostaglandins and their analogues are biologically active materials that can be absorbed through the skin.
Therefore, pregnant women and women who intend to become pregnant should take care to prevent direct exposure to the contents of the vial. If a significant amount of the contents of the bottle accidentally comes into contact with the skin, immediately and thoroughly rinse the affected area. Patients should remove contact lenses before instilling Travapress and 15 minutes after instillation before reinserting contact lenses. Impact on the ability to drive vehicles. Wed and fur.: Temporary blurred vision or other visual disturbances after using the drug may affect the ability to drive a car or use machinery. If blurred vision occurs after instillation of the drug, then the patient must wait until clear vision is restored before driving a vehicle or operating machinery.

Travoprost: Russian experience of use

E.A. Egorov, J.G. Oganezova

Department of Ophthalmology of Medical Faculty

GOU VPO Russian State Medical University of Roszdrav, Moscow

Literary review presents results of multicenter studies: “START” “Travatan long–term treatment” carried out in Russian sites during 2003–2007. It also includes results of independent research of effect and safety of Travatan usage in patients with low pressure glaucoma, angle–closed glaucoma and before phacoemulsification.

prostaglandin-type drugs stand out among other drugs used to reduce intraocular pressure (IOP) in glaucoma due to their pronounced hypotensive effect, the absence of systemic and minor local side effects, the absence of addiction, a persistent effect and a convenient mode of use (once a day), which improves quality of life of patients and increases their adherence to treatment [4,9,15, 17,27,29,30,37]. Thanks to this, having appeared on the Russian market in the late 90s of the 20th century, prostaglandins took a strong place in the treatment of patients with glaucoma.

Travatan (travoprost 0.004%) is one of the representatives of this group, celebrating this year the eighth anniversary of its successful use in the world and the fifth anniversary in Russia. During this time, a number of multicenter and initiative studies were conducted on the use of Travatan in glaucoma patients in various situations.

Study " Travatan as an alternative therapy for glaucoma"

(START)" was held in many countries of the world, including Russia, in 2003–2005. In Russia, this was a 12-week open study in 50 medical institutions, in which 1389 patients took part. The purpose of the study was to evaluate the effectiveness of Travatan in patients with newly diagnosed glaucoma and patients who had previously received antihypertensive therapy but did not achieve adequate IOP control. When analyzing the results of the Swiss [20] and Russian studies, it can be said that the average reduction in IOP one month after starting the use of a 0.004% travoprost solution was comparable. However, in the Russian study, in all comparable groups there was a greater decrease in IOP levels by the 3rd month of use. This trend can be seen in groups of patients with newly diagnosed glaucoma with a tonometric IOP of more than 25 mm Hg. (according to Maklakov), as well as patients using latanoprost, β-blockers, carbonic anhydrase inhibitors.

In this study, in all cases, both when using Travatan in patients with newly diagnosed glaucoma, and in patients who failed to achieve an adequate reduction in IOP during therapy with other antiglaucoma drugs used as mono- or combination therapy, Travatan provided additional reduction IOP from 2 to 9 mm Hg. Art. (Tables 1, 2) The magnitude of the additional reduction in IOP depended on the drug from which group of antiglaucoma drugs the patient was transferred to Travatan. However, based on the data that a decrease in IOP by 1 mm Hg. reduces the risk of glaucoma progression by 10%, Travatan gives an additional chance to preserve vision for patients with glaucoma.

Study " Travatan Long-Term Therapy"

"was carried out in more than 50 clinics in 30 cities of Russia over 9 months. Design: open, prospective, uncontrolled, non-randomized. Objective: to evaluate the effectiveness of long-term monotherapy with Travatan in patients with newly diagnosed primary open-angle glaucoma (POAG) and those in whom the glaucomatous process continued to progress despite therapy with other drugs.

1777 patients (2746 eyes) were included in the study, 1430 people (2244 eyes) completed it on Travatan monotherapy (16% of patients were transferred to combination therapy or underwent surgery).

Regardless of the previous treatment received, throughout the entire 9 months of observation, travoprost monotherapy stabilized the course of the disease, providing an additional reduction in IOP compared to the baseline (Fig. 1).

In the group of patients with newly diagnosed glaucoma with elevated IOP, after 4 weeks of travoprost monotherapy, the group average IOP was less than 21 mmHg. (initial exceeded 28 mmHg) and remained at this level until the end of the study. This result indicates not only the high hypotensive activity of the drug, but also the persistence of the effect, which was confirmed by the results of correlation analysis. However, it is worth noting that after 36 weeks of treatment, patients with stage IIIb glaucoma experienced an increase in IOP, which became significantly higher than in patients with stages I and II (ρ<0.001). This trend is natural for glaucoma, therefore, more active therapy is recommended for patients with advanced stages to achieve lower IOP values [2,5,15].

In the group of patients with newly diagnosed glaucoma with normal IOP (IOP), the decrease in IOP was less pronounced and amounted to 17.17% by the end of the study. The recommended reduction in IOP by 30% of the initial value [5] after 36 weeks of travoprost monotherapy was achieved by only 15.79% of patients with stage I glaucoma and not a single patient with stages II and III. The results obtained are consistent with literature data [10,25,39] and once again confirm the relevance of combination therapy for patients with GND and the need to search for combinations of drugs that could be used for it.

Another group with a smaller decrease in IOP than the others was the group of patients switched to travoprost treatment from latanoprost monotherapy. To date, there is no clear opinion about the advantage of one prostaglandin drug over others [18,27,28, 30,33,41]. However, it is known that travoprost has higher selectivity for FP receptors. It is the high affinity for receptors of this type that can provide a more pronounced effect on ophthalmotonus [2]. In this study, after 36 weeks, travoprost provided an additional statistically significant reduction in IOP by 14.28%. But throughout the entire observation period, the IOP level in this group was significantly higher than in other patients (p <0.02). In addition, in 15% of patients the IOP level exceeded 25 mm Hg, and in 16% of patients there was an increase in IOP compared to baseline. The results obtained indicate that in a number of patients travoprost may be more effective than latanoprost, and replacing one drug with another may provide stabilization of the glaucomatous process. But at the same time, in almost a third of patients such a change in treatment is not justified - combination therapy might be more rational for them.

Regarding the tolerability of long-term monotherapy with travoprost, no systemic side effects were recorded in any patient. Side effects were identified in 621 patients (43.43%) and were mainly represented by conjunctival hyperemia of varying severity (30.56% of cases), darkening and increased eyelash growth (7.41%). Only in 0.84% were side effects the reason for discontinuation of the drug.

It should be noted that only 0.73% of patients refused to continue participating in the study due to financial difficulties, i.e. the majority of patients demonstrated a willingness to purchase travoprost. This aspect should be taken into account by Russian ophthalmologists when prescribing treatment.

We investigated the use of combinations of prostaglandin drugs with drugs from other groups as part of an initiative study in patients with GND

. The effectiveness and tolerability of 3 combinations were compared: travoprost with betaxolol, brinzolamide, timolol. Design: long-term (6 months), open, prospective, comparative, randomized, uncontrolled.

45 patients (82 eyes) with GND were included and, after randomization, were assigned to one of the specified combinations. All combinations provided a stable reduction in IOP in all patients over the 6-month study period. However, by the end of the observation period, in no subgroup the average IOP was lower than the initial one by the recommended 30%. The combination with brinzolamide had the least hypotensive effect (Fig. 2): throughout the entire period of combination therapy, the IOP of these patients exceeded the IOP of other patients (ρ<0.03). The remaining combinations showed comparable activity.

As for perimetric indicators, all patients showed positive dynamics in increasing retinal sensitivity and reducing the number of defects, and it was the best in the subgroup additionally receiving brinzolamide, the worst in the Fotil subgroup (Fig. 3). All patients showed positive dynamics in ERG and ERG parameters, with more pronounced changes recorded in the brinzolamide subgroup.

Worse treatment tolerability was found in the Fotil subgroup: a third of patients refused to continue participating in the study due to side effects affecting their quality of life.

Thus, the combination of travoprost with brinzolamide, despite the rather weak antihypertensive activity, caused the most pronounced improvement in perimetry, ERG and ERG parameters and demonstrated good tolerability.

Such results can be explained based on the characteristics of the pathogenesis of normal pressure glaucoma, in which vascular factors, in particular ischemia and vasospase, play an important role [1]. Therefore, the doctor’s focus only on the IOP level cannot be considered correct [1,7] - when choosing a drug, one should take into account not only its hypotensive activity, but also the possible effect on hemodynamics.

We also studied the effect of prostaglandin drugs on the course of the glaucomatous process in patients with primary angle-closure glaucoma ( PACG)

). The studies described in the literature were mostly carried out on representatives of the Mongoloid race, who, due to their anatomical and physiological characteristics, are more susceptible to the development of PACG. In these patients, prostaglandins showed a high antihypertensive effect and a positive effect on ocular perfusion [12,13,19,34,38,40].

Our study involved 30 Caucasian patients (56 eyes) with laser-operated PACG. Design: duration – 3 months, open, prospective. Monotherapy with travoprost demonstrated pronounced antihypertensive activity and good tolerability. Thus, a statistically significant decrease in IOP was observed after 2 weeks and was maintained throughout the entire observation period, amounting to 20.89% of the initial value after 3 months of treatment. The ease of churn rate increased by 35%. Regarding the effect on visual function, the increase in visual acuity did not reach the level of statistical significance; the number of scotomas of 1st, 2nd and 3rd orders decreased after 3 months of treatment by 32.44, 51.92 and 48.82%, respectively (ρ<0.03). The dynamics of the ERG and ERG indicators were positive, but the changes did not reach the level of statistical significance. The most common side effect of the treatment was conjunctival hyperemia.

Thus, travoprost can also be used in patients with laser-operated PACG to stabilize IOP (which has been confirmed by foreign studies).

We also studied the effect of travoprost on the course of the postoperative period.

after phacoemulsification of cataract with intraocular lens implantation (FEC+IOL) in patients without glaucoma and with the presence of this disease. Design: duration – 2 weeks, open, prospective, comparative, randomized, controlled.

There is no consensus in the literature about the positive or negative effect of prostaglandins on the severity of postoperative reactive syndrome. A number of studies indicate the hypotensive effect of these drugs in the postoperative period [6,8,11,14,35], others do not note a significant effect on ophthalmotonus [20,21,31,32]. Some authors report the absence of side effects associated with the pre- and postoperative use of prostaglandins [16,26,36,42], others indicate an increased incidence of macular edema [23,24].

In our study, 2 hours before surgery, patients of the main groups were instilled with Travatan once; no instillation was performed in the control groups. Depending on the presence or absence of glaucoma in the operated patients, we obtained slightly different results.

In all patients, despite general measures taken to reduce intraocular and blood pressure, an increase in IOP was observed before surgery, probably associated with psycho-emotional factors. The increase in ophthalmotonus was more pronounced in the control group and among patients without glaucoma, which may indicate more active local antihypertensive therapy, which should be used even in patients without glaucoma.

Among patients with cataracts

the most pronounced increase in ophthalmotonus was observed on the 1st day after surgery (Fig. 4).

IOP in the control group during the first 5 days exceeded the IOP in the main group, which is most likely due to the greater number of patients in it with corneal edema (ρ<0.003). And a higher incidence of corneal edema could lead to lower values of visual acuity in the control group compared to the main group: thus, visual acuity was significantly higher in the travoprost group on days 3, 7 and 14 after surgery (ρ<0.04). At the same time, there were significantly more patients with conjunctival hyperemia, on the contrary, in the main group: on days 1, 2, 3 and 14 there were more in the travoprost group than in the control (ρ<0.04).

The described results allow us to conclude that it is important and necessary to prescribe to patients without glaucoma who are preparing for FEC + IOL instillation of antiglaucoma drugs both before surgery and in the first days after it, in order to influence ocular hypertension as a component of the reactive syndrome and improve visual functions.

In patients with glaucoma

2 almost equal IOP peaks were observed: on the 1st and 7th day after surgery, more pronounced in the control group than in the main group (Fig. 5).

However, there were no statistically significant differences in the level of IOP throughout the study between the control and main groups (ρ>0.07). There were again more patients with corneal edema in the control group, but in this case the differences were not statistically significant (ρ>0.06). No significant differences were found in the dynamics of visual acuity values (ρ>0.09), which may be due to the previous indicator. Among patients with glaucoma, conjunctival hyperemia was observed more often than in patients without this disease, and when comparing the control and main groups, there were significantly more patients with this phenomenon in the main group only on the 1st day after surgery (ρ<0.04).

The results obtained indicate a longer duration of the reactive syndrome in patients with glaucoma and the desirable prescription of additional local antihypertensive drugs to those received.

Summarizing the above, we can conclude that Travatan has high antihypertensive activity, good tolerability, safety and financial acceptability. This drug can be recommended for widespread use as monotherapy and in combination with drugs from other groups for the treatment of patients with POAG (including those not stabilized on existing therapy), with GND and PAOG, as well as for the preoperative preparation of patients before FEC + IOL .

Literature 1. Alyabyeva Zh.Yu., Normal pressure glaucoma and moderately high pressure glaucoma: the role of systemic and cerebral disorders in pathogenesis, clinical features, diagnosis and treatment. Abstract of thesis. for the job application scientist step. Dr. med. Sciences, 2004. 2. Egorov E. A. et al.//Ophthalmopharmacology. Moscow, Publishing house House "Geotar-Med" 2004. 3. Erichev V. P. Main directions of antihypertensive treatment of patients with primary glaucoma. Rus. ophthalmol. magazine T.1. No. 1. C. 18-21, 2000. 4. Erichev V.P., Yakubova L.V., Clinical assessment of the safety of long-term use of Xalatan (literature review). Glaucoma No. 1-2004. 5. Kuroedov A.V., Prospects for the use of combined antiglaucoma drugs (literature review). Clinical ophthalmology, 2007, volume 8, number 4 pp. 176-180. 6. Loginova N.E. Latanoprost: drug activation of uveoscleral outflow as prevention of ocular hypertension after cataract surgery. Consilium Medicum, 2001, volume 3, no. 12. 7. Nesterov A.P. Glaucoma. M. Medicine, 1995. 8. Petrov S.Yu., Shmyreva V.F., The use of travoprost as preoperative preparation for antiglaucomatous surgery. Clinical Ophthalmology, 2005, vol. 6, no. 4, pp. 166-169. 9. Alm A., Camras CB, Watson PG Phase III latanoprost studies in Scandinavia, the United Kingdom and The United States. Surv. Ophthalmol. 1997;41 Suppl 2:105-110. 10. Ang A., Reddy MA, Shepstone L., Broadway DC, Long term affect of latanoprost on intraocular pressure in normal tension glaucoma, Br. J. Ophthalmol.- 2004.- Vol. 88.- P. 630-634. 11. Arici MK, Erdogan H., Toker I., Vural A., Topalkara A., The effect of latanoprost, bimatoprost, and travoprost on intraocular pressure after cataract surgery. J. Ocul. Pharmacol. Ther. 2006; 22(1):34-40. 12. Aung T., Chan YH, Chew PT, Degree of angle closure and the intraocular pressure-lowering effect of latanoprost in subjects with chronic angle-closure glaucoma. Ophthalmology. 2005; 112(2):267-71. 13. Chew PT, Aung T., Aquino MV, Rojanapongpun P., Intraocular pressure-reducing effects and safety of latanoprost versus timolol in patients with chronic angle-closure glaucoma. Ophthalmology. 2004; 111(3):427-34. 14. Ermis SS, Ozturk F., Inan UU, Comparing the effects of travoprost and brinzolamide on intraocular pressure after phacoemulsification. Eye. 2005; 19(3):303-7. 15. European Glaucoma Society – Terminology & Guidelines for Glaucoma (European Guidelines). 2nd ed. Savona Italy: Editrice DOGMA, 2003. 16. Gaddie IB, Bennett DW, Cystoid macular edema associated with the use of latanoprost. J. Am. Optom. Assoc. 1998; 69(2):122-8. 17. Hedner J., Svedmyr N., Lunde H., Mandahl A. The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma. Surv-Ophthalmol. Feb 1997; 41 Suppl 2: S111-5. 18. Holmstrom et al.//Current medical research & opinion 2005:11;1875–1883 19. Hung PT, Hsieh JW, Chen YF, Wei T., Efficacy of latanoprost as an adjunct to medical therapy for residual angle-closure glaucoma after iridectomy. J. Ocul. Pharmacol. Ther. 2000; 16(1):43-7. 20. Kaback M., et al.// Current medical research & opinion 2004:9;1341–1345 21. Lai JS; Chua JK; Leung AT; Lam DS Latanoprost versus timolol gel to prevent ocular hypertension after phacoemulsification and intraocular lens implantation. J Cataract Refract Surg. 2000; 26(3):386-91. 22. Lai JS; Loo A.; Tham CC; Ho SY; Lam DS Preoperative latanoprost to prevent ocular hypertension after phacoemulsification and intraocular lens implantation. J Cataract Refract Surg. 2001; 27(11):1792-5. 23. Mills KB Blind randomized non-crossover long-term trial compating topical timolol 0.25% with timolol 0.5% in the treatment of simple chronic glaucoma.// Br.J. Ophthalmol.- 1983.- V.67.- N.4.-P. 216-219.113 24. Miyake K.; Ibaraki N. Prostaglandins and cystoid macular edema. Surv Ophthalmol. 2002; 47 Suppl 1:S203-18. 25. Miyake K.; Ibaraki N.; Goto Y.; Oogiya S.; Ishigaki J.; Ota I.; Miyake S. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg. 2003; 29(9):1800-10. 26. Monte S. Dirks, et al. Advances in Therapy, Volume 23 No.3, May/June 2006. A 3-Month clinical trial comparing the IOP-lowering Efficacy of Bimatoprost and Latanoprost in patients with normal-Tension Glaucoma. 27. Moroi SE, Gottfredsdottir MS, Schteingart MT, et al. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology 1999;106:1024-1029. 28. Netland PA, Landry T, Sullivan EK et al. Travoprost compared with latanoprost and timolol in patients with open–angle glaucoma or ocular hypertension. Am J Ophthalmol 2001; 132:472–84. 29. Ni Li, Xiao-ming Chen et al. – Travoprost compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials//Clinical and Experimental Ophthalmology 2006; 34: 755–64. 30. Noecker RS, Dirks MS, Choplin NT, Bernstein P, Batoosingh AL and Whitcup SM for the Bimatoprost/Latanoprost Study Group. A Six-Months Randomized Clinical Trial Comparing the IOP-Lowering Efficacy of Bimatoprost and Latanoprost in Patients With Ocular Hypertension or Glaucoma. Am J Ophthalmol 2003. 31. Parrish RK, Palmberg P, Sheu WP et al. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12–week, randomized, masked–evaluator multicenter study. Am J Ophthalmol 2003; 135:688–703. 32. Rainer G.; Menapace R.; Findl O.; Peternel V.; Kiss B.; Georgopoulos M. Intraindividual comparison of the effects of a fixed dorzolamide-timolol combination and latanoprost on intraocular pressure after small incision cataract surgery. J Cataract Refract Surg. 2001; 27(5):706-10 33. Rainer G.; Menapace R.; Schmetterer K.; Findl O.; Georgopoulos M.; Vass C. Effect of dorzolamide and latanoprost on intraocular pressure after small incision cataract surgery. J Cataract Refract Surg. 1999; 25(12):1624-9. 34. Rikket van der Valk et al. IOP–lowering effects of glaucoma drugs: summary of a recent meta–analysis. View on Glaucoma 2006; 1(1): 14–6. 35. Sakai H.; Shinjyo S.; Nakamura Y.; Ishikawa S.; Sawaguchi S., Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients. J Ocul Pharmacol Ther. 2005; 21(6):483-9. 36. Scherer WJ; Mielke DL; Tidwell PE; Hauber FA Effect of latanoprost on intraocular pressure following cataract extraction. J Cataract Refract Surg. 1998; 24(7):964-7 37. Schumer RA; Camras CB; Mandahl AK Putative side effects of prostaglandin analogs. Surv Ophthalmol. 2002; 47 Suppl 1:S219 38. Shaaravy T, Flammer J. Glaucoma Therapy. Current Issues and Controversies. Ed. Martin Dunitz. London and New York. - 2004. - P. 64-170 39. Sihota R.; Saxena R.; Agarwal H.C.; Gulati V., Crossover comparison of timolol and latanoprost in chronic primary angle-closure glaucoma. Arch Ophthalmol. 2004; 122(2):185-9. 40. Tomita G.; Araie M.; Kitazawa Y.; Tsukahara S. A three-year prospective, randomized and open comparison between latanoprost and timolol in Japanese normal-tension glaucoma patients. Eye. 2004; 18(10):984-9. 41. Wang N.; Fan Z.; Wu H.; Li D.; Huang Y.; Chen J.; Lin H., Drug therapy for residual angle-closure glaucoma after laser iridectomy. Zhonghua Yan Ke Za Zhi. 2002; 38(12):712-6. 42. Wilensky J., et al. // Am J Ophthal 2006; 141: S28–33 43. Yeh PC; Ramanathan SJ Cataract Refract Surg. 2002; 28(10):1814-8

Description of the drug TRAVAPRESS PLUS

Like other topical ophthalmic agents, travoprost and timolol are absorbed into the systemic circulation. Due to the presence of timolol, which has a beta-blocking effect, the drug may develop the same types of adverse reactions from the cardiovascular system, lungs and other organs as when using systemic beta-blockers.

Heart disorders

In patients with diseases of the cardiovascular system (for example, coronary artery disease, Prinzmetal's angina, heart failure) and arterial hypotension, the appropriateness of using beta-blockers should be critically assessed and the possibility of using other active substances should be considered. Patients with cardiovascular diseases should be assessed for signs of worsening of these diseases and the development of adverse reactions. Because beta blockers have a negative effect on conduction time, they should be used with caution in patients with first-degree AV block.

Vascular disorders

In patients with severe impairments or diseases of the peripheral circulation (i.e. severe forms of Raynaud's disease or Raynaud's syndrome), treatment should be carried out with caution.

Breathing disorders

The patient's condition should be monitored before and during timolol therapy. After the use of certain ophthalmic drugs from the group of beta-blockers, cases of respiratory reactions, including death from bronchospasm, have been described in patients suffering from bronchial asthma.

In patients with mild to moderate COPD, the drug should be used with caution and only if the expected benefit outweighs the possible risk.

Hypoglycemia/diabetes mellitus

In patients prone to developing spontaneous hypoglycemia, as well as in patients with labile diabetes mellitus, beta-blockers should be used with caution, as they may mask the signs and symptoms of acute hypoglycemia.

Hyperthyroidism

Beta blockers may mask signs of hyperthyroidism.

Muscle weakness

It has been reported that beta blockers may potentiate muscle weakness, consistent with certain symptoms of myasthenia gravis (eg, diplopia, ptosis, and generalized muscle weakness).

Corneal diseases

Beta blockers for ophthalmic use may cause dry eyes. In patients with corneal diseases, the drug should be used with caution.

Choroidal detachment

In patients who used drugs that suppress the production of aqueous humor (for example, timolol and acetazolamide), cases of choroidal detachment were observed after fistulizing operations of the organ of vision.

Other beta blockers

When timolol is used in patients already taking systemic beta-blockers, the effect on intraocular pressure or other known effects of systemic beta-blockers may be enhanced. The response to therapy in such patients should be carefully monitored. The use of two beta-blockers for topical use is not recommended.

Skin contact

Prostaglandins and prostaglandin analogues are biologically active substances that can be absorbed through the skin. Women during pregnancy and women planning pregnancy should take appropriate precautions to avoid direct contact with the skin. If a significant portion of the product does come into contact with the skin (which is unlikely), the area of skin on which the product has come into contact should be immediately rinsed with water.

Anaphylactic reactions

The use of timolol in patients with atopy or a history of severe pathological reactions to various allergens may provoke more severe reactions in response to the introduction of various allergens. Such patients may respond poorly to normal doses of epinephrine to relieve anaphylactic reactions.

Effects on the eyes

This medication can gradually change eye color by increasing the number of melanosomes (pigment granules) in melanocytes. Before starting treatment, patients should be informed about the possibility of permanent changes in eye color. Treatment of only one eye can lead to permanent heterochromia. The long-term effect on melanocytes and the consequences of this influence are currently unknown. The change in iris color occurs slowly and may not be noticeable for months or years.

Changes in eye color are predominantly observed in patients with mixed iris colors (blue-brown, gray-brown, yellow-brown or green-brown), a similar effect was observed in patients with brown eyes. In typical cases, brown pigmentation around the pupil extends concentrically to the periphery of the iris; as a result, the entire iris or parts thereof acquire a browner color. After completion of therapy, no further accumulation of brown pigment was observed in the iris.

Darkening of the skin in the periorbital area and/or eyelids has been reported with use of this product.

This remedy may gradually change the condition of the eyelashes in the treated eye(s); These changes include changes in length, thickness, pigmentation and/or number of eyelashes.

The mechanism of these changes is currently unknown.

Macular edema has been reported during treatment with prostaglandin F2α analogues. The drug should be used with caution in patients with neovascular, closed-angle (narrow-angle) glaucoma, pigmentary and congenital glaucoma, open-angle glaucoma with pseudophakia, pseudoexfoliative glaucoma, inflammatory diseases of the organ of vision, aphakia, pseudophakia with rupture of the posterior capsule of the lens or anterior chamber intraocular lens, as well as patients with risk factors for macular edema, iritis, uveitis.

When using prostaglandin analogs, changes in the periorbital area and eyelids were noted.

Anesthesia for surgical interventions

Ophthalmic drugs from the group of beta-blockers can suppress the beta-agonist effects, for example, of epinephrine. The anesthesiologist should be informed if the patient is receiving timolol.

Contact lenses

Patients should be instructed to remove contact lenses before using this product and to wait at least 15 minutes before reusing them.

Impact on the ability to drive vehicles and machinery

Temporary blurred vision or other vision disturbances after using this product may affect your ability to drive or use machinery. If blurred vision occurs after using the product, the patient must wait until clear vision is restored before driving a vehicle or operating machinery.