Expiration date: 03/2025

The composition and form of issue:

Eye drops. 1 ml contains:

latanoprost 50 micrograms

timolol maleate of 6.83 mg (equivalent to 5 mg timolol)

Excipients: benzalkonium chloride (50% solution), sodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium chloride, water for injections*

* if necessary (for pH) was added to a solution of hydrochloric acid 10% or sodium hydroxide solution 10% q.s.

in a bottle-kapelnica PE 2.5 ml in a cardboard pack 1 bottle.

Description pharmaceutical form:

Clear, colorless solution.

Pharmacokinetics:

Pharmacokinetic interactions between latanoprost and timolol maleate is not installed, although through 1-4 h after application of the combination drug concentration of the acid latanoprosta in watery moisture was approximately 2 times higher than with monotherapy.

Latanoprost

Suction. Latanoprost, being a Pro-form that is absorbed through the cornea where it is hydrolysis to the biologically active acid. The concentration in the watery moisture reaches a maximum of about 2 hours after topical application.

Distribution. Vd is (0,16±0,02) l/kg. Acid latanoprosta defined in watery moisture during the first 4 hours and in plasma only during the first hour after local administration.

Metabolism. Latanoprost is hydrolyzed in the cornea under the action of esterases with the formation of the biologically active acid. Acid latanoprosta entering the systemic circulation is metabolized primarily in the liver by beta-oxidation of fatty acids with the formation of the 1,2-dinor - and 1,2,3,4-tetranor-metabolites.

Excretion. Latanoprost acid is rapidly eliminated from plasma (T1/2 =17 min). Systemic clearance is approximately 7 ml/min/kg. Metabolites are excreted mainly by the kidneys: after topical application with a urine output of approximately 88% of the administered dose.

Timolol maleate. The concentration of timolol maleate in the aqueous humor of the moisture reaches a maximum approximately 1 h after application of eye drops. Part of the dose undergoes systemic absorption, Cmax in plasma, component 1 ng/ml is reached 10-20 minutes after application of the drug is one drop in each eye 1 time per day (300 mg/day). T1/2 of timolol maleate in plasma is about 6 h. Timolol maleate is extensively metabolized in the liver. Metabolites and some unchanged timolol maleate are excreted in the urine.

Description pharmacological action:

The preparation of Xalacom consists of 2 active ingredients — latanoprost and timolol maleate. The mechanism for the reduction of elevated intraocular pressure (IOP) in these components is different, which provides additional reduction in IOP compared with the effect dostigayutsya in the application of each of these components as monotherapy.

Latanoprost is a selective agonist of the FP receptor prostanoid and reduces IOP by increasing the outflow of aqueous humor, mainly through the uveoscleral and also through the trabecular meshwork. Found that latanoprost has no significant effect on products watery moisture and gematoentsefalichesky barrier. For short-term treatment of latanoprost does not cause leakage of flûorescina, & nbsp; in the posterior segment of the eye with pseudophakia. When used in therapeutic doses, latanoprost has no significant pharmacological effect on the cardiovascular system and the respiratory system.

Timolol is a nonselective &beta1 - and beta2-blocker, which does not possess significant intrinsic sympathomimetic activity, — has no direct depressive effects on the myocardium or local anesthetic (membrane stabilizing) effect.

Blockade of beta-adrenergic receptors causes a decrease in cardiac output in healthy people and patients with heart disease. Patients with severe dysfunction of the myocardium beta-blockers can inhibit the stimulating effect of the sympathetic nervous system, necessary for the proper functioning of the heart.

Blockade of beta-adrenergic receptors in the bronchi and bronchioles leading to increased airway resistance under the influence of the parasympathetic nervous system. A similar effect can be dangerous for people with asthma and other bronchospastic diseases (see sections "Contraindications" and "Special instructions").

The application of timolola maleate in eye drops causes a decrease in the elevated and normal IOP, regardless of the presence or absence of glaucoma. Elevated IOP is the main risk factor for glaucomatous loss of visual fields. The higher the IOP, the greater the likelihood of glaucomatous visual field loss and optic nerve damage.

The exact mechanism of lowering IOP under the action of timolol maleate is not installed. The results of tonography and fluorophotometry indicate that the primary mechanism of action may be associated with a decrease in the formation of aqueous humor. However, some studies have noted a small increase in the outflow.

Action combination latanoprost and timolol maleate starts within one hour and maximal effect occurs within 6-8 h.

By repeated application of adequate reduction in IOP persists for 24 hours after injection.

Indications:

Reduction of elevated IOP in patients with open-angle glaucoma or high IOP at the lack of effectiveness of other drugs for local application to reduce IOP.

Contraindications:

• hypersensitivity to latanoprost, timolol maleate or the other components of the drug
  
• COPD heavy currents
  
• sinus bradycardia
  
• AV blockade II–III degree
  
• clinically severe heart failure, cardiogenic shock
  
• reactive airway disease including bronchial asthma (or indication of its history).
  

With caution:

• inflammatory, neovascular, angle closure or congenital glaucoma
  
• open-angle glaucoma in combination pseudophakic
  
• pigmentary glaucoma (due to the lack of sufficient experience with the drug)
  
• the aphakia, pseudophakia with rupture of the posterior lens capsule, patients with known risk factors for macular edema (when treating latanoprost described cases of macular edema, including cystoidea).
  

Application of pregnancy and breast-feeding:

Adequate controlled studies in pregnant women have not been conducted. The drug should be administered during pregnancy only in those cases when the potential benefit outweighs the potential risk to the fetus.

Latanoprost and its metabolites may be released in breast milk. Timolol maleate, when used in the form of eye drops, is also found in breast milk. Given the risk of serious adverse reactions in infants, breastfeeding and the importance of the drug to the mother should either stop breast-feeding or stop the drug.

Safety and effectiveness in children have not been established.

Side effects:

In applying the drug with Xalacom was listed below adverse reactions with frequency &GE. 1%.

On the part of the organ of vision: blurred vision, blepharitis, cataract, conjunctivitis, lesions of the conjunctiva (follicles, papillary reaction of the conjunctiva, petechiae, etc.), lesions of the cornea (erosion, pigmentation, point keratitis, etc.), disorders of refraction, eye hyperemia, eye irritation, eye pain, increased iris pigmentation, keratitis, photophobia, loss of visual fields.

Infection: sinusitis, infections of the upper respiratory tract and other infections.

Disorders of metabolism and nutrition: diabetes and hypercholesterolemia.

Mental disorders: depression.

From the nervous system: headache.

Vascular disorders: hypertension.

On the part of the skin and subcutaneous tissues: hypertrichosis, rash, and skin changes (irritation, dermatochalasis, etc.).

From the side of musculoskeletal system and connective tissue: arthritis.

Listed below are other adverse events observed in monotherapy individual components of the drug Xalacom (in addition to the above).

Latanoprost

On the part of the organ of vision: eye irritation (burning sensation, feeling of sand in eyes, itching, stinging and foreign body sensation), transient point of erosion of epithelium, swelling of the eyelids, swelling and erosion cornea lengthening, thickening, increased numbers and increased pigmentation of eyelashes and downy hair iritis/uveitis macular edema, including custody changing the direction of eyelash growth, sometimes causes eye irritation blurred vision.

On the part of the skin and subcutaneous tissue: skin rash, darkening of the eyelid skin and local skin reactions on the eyelids.

From the nervous system: dizziness.

From the side of respiratory system: asthma (including acute attacks or exacerbation of the disease in patients with bronchial asthma in history), shortness of breath.

From the side of musculoskeletal system and connective tissue: pain in muscles/joints.

General and local reactions: nonspecific chest pain.

Timolol maleate (eye drops)

The immune system: systemic allergic reactions, including anaphylaxis, angioedema, urticaria, localized and generalized rash.

Disorders of metabolism and nutrition: anorexia, hidden symptoms of hypoglycemia in patients with diabetes mellitus.

Mental disorders: changes behavior and mental disorders, including confusion, hallucinations, anxiety, disorientation, nervousness, memory loss, decreased libido, insomnia and nightmares.

From the nervous system: ischemia of the brain, acute violation of cerebral circulation, dizziness, increased symptoms of myasthenia gravis, paresthesia, somnolence, fainting.

Side of body: custody macular edema, decreased sensitivity of the cornea with detachment of the choroid after filtration surgery ptosis, visual disturbances, including refractive changes and diplopia.

On the part of the organ of hearing and vestibular: tinnitus.

Cardiac complications: arrhythmia, bradycardia, cardiac arrest, heart failure, heart block, palpitations, progression of angina.

Vascular disorders: intermittent claudication, cold hands and feet, hypotension, Raynaud's syndrome.

From the side of respiratory system: bronchospasm (mainly in patients with previous bronchospastic disease), cough, shortness of breath, nasal congestion, pulmonary edema and respiratory failure.

Gastrointestinal: diarrhea, dry mouth, dyspepsia, nausea, retroperitoneal fibrosis.

On the part of the skin and subcutaneous tissue: alopecia, pseudopemphigoid, psoriasiform rash or exacerbation of psoriasis.

From the side of musculoskeletal system and connective tissue: systemic lupus erythematosus.

From the reproductive system and mammary glands: impotence, Peyronie's disease.

General and local: asthenia/fatigue, chest pain, swelling.

Drug interactions:

Drug interaction with Xalacom with other drugs is not specifically studied.

In applying the drug with Xalacom patients receiving beta-blocker inside, perhaps a more pronounced decrease in IOP or increased systemic manifestations of beta-adrenoblokatorov, so simultaneous local application of two or more of beta-blockers is not recommended.

With the simultaneous instillation into the eyes of two analogs of PG described the paradoxical elevation of IOP, so the simultaneous use of two or more of PG, their analogues or derivatives is not recommended.

While the use of timolol maleate with adrenaline sometimes developed mydriasis.

The combination of timolol maleate with the following drugs possible additive effect with the development of systemic hypotension and/or severe bradycardia:

• BKK
  
• means for causing a decrease in the level of catecholamines or beta-blockers
  
• antiarrhythmic agents
  
• cardiac glycosides.
  

Beta-blockers may enhance the hypoglycemic effect of antidiabetic agents.

Method of application and dose:

Adults (including the elderly) 1 drop in affected eye(s) 1 times per day.

Overdose:

Below is information about the symptoms of an overdose two components of the drug.

Latanoprost

In addition to eye irritation and hyperemia of the conjunctiva, other undesirable changes in the organ of vision in overdose latanoprost unknown.

If you accidentally taking latanoprost inside, note the following information: 1 vial with 2.5 ml of solution contains 125 µg latanoprost. More than 90% of drug is metabolized in the first pass through the liver. The on/in infusion at a dose of 3 mg/kg in healthy volunteers did not cause any symptoms, but with the introduction of a dose of 5.5–10 µg/kg were observed nausea, abdominal pain, dizziness, fatigue, hot flashes and sweating. In patients with bronchial asthma of moderate severity introduction latanoprost in the eye in a dose, in 7 times the therapeutic does not cause bronchospasm.

Timolol maleate

Cases of unintentional overdose of eye drops of timolol maleate, resulting in the observed systemic effects, similar to those with systemic use of beta-blockers: dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest. (see "Side effects").

In vitro study it was shown that in dialysis timolol is easily derived from plasma or whole blood.

In patients with renal insufficiency timolol was dializiruetsa worse.

Treatment: in case of overdose, symptomatic treatment.

Special instructions:

Drug Xalacom should be applied no more than once per day, as more frequent administration latanoprost leads to a weakening of the IOP reducing effect.

When skipping one dose, the next dose should be administered at the usual time.

If the patient is simultaneously use other eye drops, they should be used with interval of at least 5 min.

The preparation of Xalacom's included benzalkonium chloride which may be absorbed by contact lenses. Before eyedrops contact lenses, you must remove and re-install them after 15 minutes.

Latanoprost. Can cause a gradual increase in the content of brown pigment in the iris. Change the eye color due to increased melanin content in stromal melanocytes of the iris, not the increase in the number of melanocytes themselves. In typical cases, the brown pigmentation appears around the pupil and spreads concentrically to the periphery of the iris. The entire iris or parts of it become brown. In most cases the color change is slight and may not be established clinically. Increased pigmentation of the iris of one or both eyes has been observed mainly in patients with mixed colour irides that contain the basis of brown color. The drug has no effect on nevi and lentigo iris pigment accumulation in the trabecular network or in the anterior chamber was not noted.

In determining the degree of pigmentation of the iris for more than 5 years revealed no undesirable effects of increased pigmentation even with continued therapy latanoprost. Patients the degree of reduction of IOP was similar, regardless of the presence or absence of increased pigmentation of the iris. Therefore, treatment with latanoprost can be continued in cases of increased pigmentation of the iris. Such patients should be under regular supervision, and, depending on the clinical situation, treatment may be discontinued.

Increased pigmentation of the iris is usually observed during the first year after initiation of treatment, rarely during the second or third year. After the fourth year of treatment this effect was not observed. The rate of progression of pigmentation decreases with time and stabiliziruemost after 5 years. In a more long-term effects of increased pigmentation of the iris has not been studied. After stopping treatment enhance brown pigmentation of the iris is not mentioned, however, change the color of the eyes can be irreversible.

In connection with the use of latanoprosta described cases of darkening of the eyelid skin which may be reversible.

Latanoprost may cause a gradual change in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased thickness and changing the direction of eyelash growth. Eyelash changes are reversible and disappear after cessation of treatment.

In patients, applying drops only in one eye may develop heterochromia.

Timolol maleate

The local application of beta-blockers could experience the same adverse reactions as and when they are administered systemically. Patients with severe cardiac disease, history should be continuously monitored in order to detect symptoms of heart failure. The local application timolola maleate can cause the following response from the heart and the respiratory system: the progression of angina Prinzmetala, as well as peripheral and Central circulatory disorders, hypotension, heart failure with fatal outcome, severe reaction in the respiratory system, including bronchospasm with fatal outcome in patients with asthma, bradycardia.

Before undertaking extensive surgical intervention, you should discuss the appropriateness of a gradual cancellation of beta-adrenoblokatorov. Drugs in this group disturb the heart's ability to response to reflex beta-adrenergic stimulation, which may increase the risk of General anesthesia. Described cases of protracted severe hypotension during anesthesia and difficulty in restoring and maintaining heart rate. During surgery, the effects of beta-blockers can be eliminated by sufficient doses of adrenergic agonists.

Beta-blockers may enhance the hypoglycemic effect of antidiabetic drugs and mask the symptoms and signs of hypoglycemia. They should be used with caution in patients with spontaneous hypoglycemia or diabetes (especially labile currents), receiving insulin or oral hypoglycemic funds.

Therapy beta-blockers may mask some of the basic symptoms and signs of hyperthyroidism. Abrupt cessation of treatment may cause worsening of the disease.

In the treatment of beta-blockers in patients with atopy or severe anaphylactic reactions to various allergens in history may increase response by repeated contact with these allergens. The adrenaline in normal doses used for the relief of anaphylactic reactions, may be ineffective.

In rare cases, the timolol maleate caused increased muscle weakness in patients with myasthenia gravis or myasthenic symptoms (e.g. diplopia, ptosis, generalized weakness).

When applying a means of reducing IOP, described the choroidal detachment after filtration procedures.

Effects on ability to drive and other mechanisms. The use of eye drops may cause transient blurring of vision. While this effect does not disappear, patients should not drive or use machinery.

Storage conditions:

Clear skin, when t is not higher than 25 °C, use within 4 weeks.