Index of drugs

Reduction of elevated intraocular pressure in patients with open-angle glaucoma and intraocular hypertension who have an inadequate response to beta-blockers or prostaglandin analogs.

1 ml drops contains 50 μg latanoprost and 5 mg Timolol (as maleate). The preparation contains benzalkonium chloride.

The product contains two active substances that reduce intraocular pressure due to different mechanisms of action. The combined effects of both drugs cause a greater decrease in intraocular pressure compared to the treatment of each drug used separately. Latanoprost is an analog of prostaglandin F_2α, a selective prostanoid FP receptor agonist. It lowers the intra-ocular pressure by increasing the outflow of aqueous humor - increases the flow of the choroid-scleral and reduces the resistance of the outflow through the trabecular meshwork. It has no significant effect on the production of aqueous humor and on the blood-liquid water barrier as well as on intraocular blood circulation. After application to the conjunctival sac, it is absorbed through the cornea and is hydrolysed to the biologically active latanoprost acid. The maximum concentration of the drug in the aqueous humor occurs approximately 2 hours after administration. T_0,5 in plasma is about 17 min. After topical administration, the systemic bioavailability of latanoprostic acid is 45%. Latanoprost acid binds to plasma proteins in 87%. Metabolism occurs mainly in the liver. Inactive metabolites are mainly excreted in the urine. Timolol is a non-selective beta-blocker, lacking intrinsic sympathomimetic activity, direct inhibition of myocardial function and nonspecific stabilizing of the membrane. Timolol reduces intraocular pressure by reducing the production of aqueous humor in the ciliary epithelium. There was no significant effect on the permeability of the blood-liquid barrier to plasma proteins. The maximum concentration in aqueous humor occurs after about 1 hour after local instillation of the drug. Part of the dose penetrates into the bloodstream - the maximum plasma concentration is reached after 10-20 min. T_0,5 in plasma is 6 h. Metabolism occurs in the liver. Timolol metabolites are excreted in the urine along with part of the drug in unchanged form. There is a tendency to maintain a 2-fold higher concentrations of latanoprost in the aqueous humor after 1-4 hours from the administration of eye drops containing latanoprost and Timolol, compared to monotherapy.

Hypersensitivity to the active substances or to any of the excipients. Bronchial hyperreactivity, including bronchial asthma currently or in history, severe chronic obstructive pulmonary disease. Sinus bradycardia, sick sinus syndrome, sinus-atrioventricular block, atrio-ventricular block IIst. or IIIst. uncontrolled with a pacemaker, overt cardiac failure, cardiogenic shock.

Due to the content of β-blocker during the application of the preparation, adverse reactions occurring during the general use of β-blockers may occur (less frequently than after the general administration). In patients with cardiovascular disease (eg coronary heart disease, Prinzmetal's angina and heart failure) and hypotension, β-blocker therapy should be carefully evaluated and other medication should be considered. Patients with cardiovascular disease should be monitored for deterioration of existing diseases and side effects. In patients with heart block Ist. β-blockers should be used with caution due to their adverse effect on conduction time. Caution should be exercised in patients with severe peripheral circulatory disturbances (eg severe Raynaud's disease or Raynaud's syndrome). In patients with mild to moderate chronic obstructive pulmonary disease, the product should be used with caution and only if the potential benefit outweighs the risk.β-blockers should be used with caution in patients prone to self-hypoglycaemia or patients with unstable diabetes (beta-blockers may mask the symptoms of acute hypoglycaemia). Β-blockers can also mask the symptoms of hyperthyroidism. Ophthalmologic preparations containing β-blockers may cause dry eye - care should be taken in patients with corneal diseases. During treatment with beta-blockers, patients with a history of atopic disease or severe anaphylactic reactions caused by a variety of allergens may be more sensitive to re-exposure to these allergens and show no response to the doses of epinephrine usually used to treat anaphylactic reactions. Co-administration of timolol with another β-adrenergic with a general effect may lead to increased intraocular pressure or known effects associated with systemic β-adrenergic blockade - patients' reactions should be carefully monitored. Co-administration of two topically administered β-blockers or two topically-applied preparations containing prostaglandins is not recommended. Latanoprost can gradually change the eye color by increasing the amount of brown pigment in the iris. It has not been proven that the change in the color of the iris is accompanied by other symptoms or pathological changes. Color changes can be permanent. Patients should be tested regularly and if the iris pigmentation increases and the clinical condition so requires treatment should be discontinued. There is no documented experience regarding the use of latanoprost in inflammatory and neovascular glaucoma, or glaucoma of a closed angle or congenital glaucoma, open-angle glaucoma in patients with pseudophakia and pigmented glaucoma. Latanoprost has no effect on the pupil or is insignificant, however, there is no experience regarding the use of acute glaucoma attacks with a closed angle. Therefore, caution should be exercised when administering the preparation in these disease states until more clinical data is available. Due to the risk of macular edema, including cystic macular edema in patients with aphasia, patients with pseudophakia with discontinued posterior capsule and patients with known risk factors for macular edema, the preparation should be used with caution. When using agents that inhibit the production of aqueous humor (eg timolol, acetazolamide), cases of choroidal dissection have been reported after filtration. Ophthalmic preparations containing β-blockers can suppress the systemic effects of β-agonists, e.g. adrenaline - inform the anesthetist if the patient is using timolol. The preparation contains benzalkonium chloride, which can cause punctate keratopathy and / or toxic ulcerative keratopathy, eye irritation and discoloration of soft contact lenses. Patients with dry eye syndrome or those with corneal injury that use the product frequently or for long periods of time should be carefully monitored. Before using the product, the contact lenses should be removed and not worn earlier than after 15 minutes. Eye drops containing timolol should be used with caution in juvenile glaucoma patients. It is important to inform parents about the possibility of side effects, so that they can immediately stop the use of the drug. Symptoms to monitor are, for example, coughing and wheezing. Due to the possibility of Cheyne-Stokes apnea and breathing, this drug should be used with special caution in newborns, infants and younger children. A portable apnea monitoring device for newborns can be used in children treated with timolol.

The preparation should not be used during pregnancy and breastfeeding.

Very common: increased pigmentation of the iris (especially in patients with iris of mixed color, eg green-brown, yellow-brown or blue / gray-brown, change in the color of the iris is very slow, not associated with other symptoms or pathological changes, can be stable, in patients with a homogeneous blue, gray, green or brown eye color the change of color is extremely rare). Common: eye irritation (including pricking, burning and pruritus), eye pain.Uncommon: headache, conjunctival hyperemia, conjunctivitis, blurred vision, increased tearing, eyelid inflammation, corneal disease, rash, pruritus. Additional side effects specific for the individual active ingredients of the preparation. Latanoprost: dizziness, changes in the appearance of eyelashes (lengthening, thickening, darkening, increase in volume), punctate epithelial defects, periorbital edema, iritis / uveitis, macular edema (in patients with aphasia, pseudophakia with discontinued posterior capsule, as well as patients at risk for macular edema), dry eyes, keratitis, edema and corneal defects, changes in the direction of eyelashes (which may cause eye irritation), iris cyst, worsening of pre-existing angina, palpitations, asthma, exacerbation asthma, shortness of breath, dark eyelid skin, joint pain, muscle pain, pain in the chest area. Timolol: systemic allergic reactions (including angioneurotic edema, urticaria, local or generalized rash, pruritus, anaphylactic reactions), hypoglycaemia, depression, memory loss, insomnia, nightmares, dizziness, paresthesia, cerebral ischemia, cerebrovascular accident, exacerbation signs and symptoms of myasthenia gravis, syncope, headache, signs and symptoms of eye irritation (eg burning sensation, pinching, pruritus, tearing, redness), keratitis, visual disturbances and choroidal detachment after filtration, reduced corneal sensitivity, dry eyes , keratitis, diplopia, eyelid droop, tinnitus, palpitations, arrhythmia, bradycardia, chest pain, swelling, cardiac arrest, atrioventricular block, congestive heart failure, arrhythmias, reduced blood pressure, Raynaud's symptom, cold hands and a stop y, bronchospasm (mainly in patients with pre-existing bronchial spasticity), dyspnea, cough, taste disturbances, nausea, diarrhea, digestive disorders, dry mouth, abdominal pain, vomiting, hair loss, psoriasis, psoriasis-like rash or exacerbation psoriasis, skin rash, sexual dysfunction, reduced sex drive, weakness / fatigue.

Adults (including elderly patients): 1 drop for the eye or both eyes affected by the disease once a day. If you miss one dose, continue with the Next scheduled dose. Occlusion of the naso-lacrimal duct or occlusion of the eyelids 2 min after administration reduces systemic absorption. If other topical ophthalmic medications are used, they should be administered after at least a 5-minute interval.Children and youth. Due to the limited amount of data, timolol may be recommended temporarily only in the treatment of primary congenital glaucoma and primary juvenile glaucoma until a surgical decision is made or in the case of lack of efficacy of the procedure, at the time of making a decision on how to proceed. Doctors considering the use of timolol in children or adolescents should carefully assess the risk-benefit ratio. Before using timolol, a detailed interview and testing for systemic disorders should be performed. There are no specific dosing recommendations because clinical data are limited. However, if the benefit exceeds the risk, it is recommended to use the active substance at the lowest concentration once a day. If the intraocular pressure is not sufficiently reduced, a careful dose increase of up to 2 drops per day to the affected eye should be considered. When administered twice a day, a 12-hour interval should be maintained. In addition, children, especially newborns, should be left in the office and subjected to strict observation for 1-2 h after the first administration and carefully monitored for ocular and systemic side effects until performance of the procedure. In children and adolescents, the active substance may be sufficient in a concentration of 0.1%. In order to limit the occurrence of potential adverse reactions, only one drop should be given at one time. Systemic absorption of topically administered β-blockers can be reduced by compressing the nasolabial lobe mouth and keeping closed eyes for as long as possible (e.g., for 3-5 min) after instillation. The drug is intended for short-term treatment of children and adolescents