Instruction for use: Xalacom

Active substance: Latanoprost + Timolol

ATX Code S01ED51 timolol in combination with other drugs

Pharmacotherapeutic group:

Beta-blockers in combination

Prostaglandins, thromboxanes, leukotrienes, and combinations of their antagonists in

Ophthalmic agents in combination

The nosological classification (ICD-10)

H40 Glaucoma

glaucoma intervention., Afakicheskaya glaucoma, narrow-angle glaucoma, Chronic glaucoma, Chronic open-angle glaucoma, Wide-angle glaucoma

H40.0 Suspected glaucoma

Marked rise in intraocular pressure, Hypertension eyes, ocular hypertension, Measurement of intraocular pressure, ophthalmohypertension, Elevated IOP, Elevated intraocular pressure, Elevated intraocular pressure in infectious diseases of the eye, Povyshennore intraocular pressure, Increased ophthalmotonus, Spontaneous blockade angle opposite eye, Narrow chamber angle, Iatrogenic, blockade angle opposite eye

H40.1 Primary open-angle glaucoma

open-angle glaucoma, Open-angle glaucoma, Primary glaucoma, pseudoexfoliation glaucoma, Elevated IOP

Composition

Eye drops 1 ml

latanoprost 50 mcg

timolol maleate 6.83 mg

(Equivalent to 5 mg of timolol)

Other ingredients: benzalkonium chloride (as a 50% solution), sodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium chloride, water for injection *

* When necessary (for pH) solution is added 10% hydrochloric acid or 10% sodium hydroxide solution - q.s.

vial-dropper PE 2.5 ml; In the paper cartons 1 vial.

The drug forms

The clear, colorless solution.

Pharmacological Properties
Pharmachologic effect

antianginal, antihypertensive, anti-arrhythmic.

Selectively blocking beta1-adrenergic receptors.

pharmacodynamics

antiglaucoma.

pharmacodynamics

The composition of the drug Ksalakom® includes 2 active component - latanoprost and timolol maleate. The mechanism of lowering elevated intraocular pressure (IOP) in these different components, which provides an additional reduction in IOP compared to the effect achieved in the application of each of these components in monotherapy.

Latanoprost - PGF2α analogue - is a selective prostanoid FP receptor agonist and lowers intraocular pressure by increasing the outflow of aqueous humor through the uveoscleral mostly and through the trabecular meshwork. It was found that latanoprost has no significant effect on the production of aqueous humor and blood-barrier. During the short-term treatment of latanoprost does not cause leakage of fluorescein in the rear segment of the eye when psevdofakii. In the application of latanoprost at therapeutic doses has no significant pharmacological effects on the cardiovascular system and respiratory system.

Nonselective timolol β1- and β2-adrenergic blocker, which does not have significant intrinsic sympathomimetic activity - has no direct depressive effect on the myocardium, or local anesthetic (membrane stabilizing) effect.

Beta-adrenoceptor blockade causes a decrease in cardiac output in healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function of beta-blockers may inhibit the stimulatory effect of the sympathetic nervous system, necessary for adequate heart.

Beta-adrenoceptor blockade in the bronchi and bronchioles leading to increased airway resistance caused by the parasympathetic nervous system. A similar effect can be dangerous for people with asthma and other diseases bronhospasticheskimi (see. Sections "Contraindications" and "Special Instructions").

The use of timolol maleate eye drops and causes the reduction of elevated IOP normal regardless of the presence or absence of glaucoma. Elevated intraocular pressure is a major risk factor for glaucomatous visual field loss. The higher the IOP, the greater the likelihood of glaucomatous visual field loss and optic nerve damage.

The exact mechanism of action for lowering IOP is not installed timolol maleate. Results tonography and fluorofotometrii indicate that the main mechanism of action may be associated with a decrease in the formation of aqueous humor. However, some studies have also noted a slight increase outflow.

Effect of the combination of latanoprost and timolol maleate begins within hours, but the maximum effect is observed for 6-8 hours.

Repeated application of adequate IOP reduction maintained for 24 hours after administration.

Pharmacokinetics

Pharmacokinetic interactions between latanoprost and timolol maleate not been established, but after 1-4 hours after the application of combined drug latanoprost acid concentration in the aqueous humor was about 2 times higher than with monotherapy.

latanoprost

Suction. Latanoprost, prodrug being sucked through the cornea where it is biologically active hydrolysis to acids. The concentration in the aqueous humor reached the maximum after about 2 hours after topical application.

Distribution. Vd is (0,16 ± 0,02) l / kg. latanoprost acid in the aqueous humor is determined during the first 4 hours and plasma - only during the first hour after topical application.

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

Withdrawal. latanoprost acid is rapidly eliminated from plasma (T1 / 2 = 17 min). Systemic clearance is approximately 7 mL / min / kg. Metabolites derived mainly kidneys: after topical application with urine output approximately 88% of the administered dose.

Timolol maleate. The concentration of timolol maleate in aqueous humor reaches a maximum after about 1 hour after application of eye drops. Part of the dose systemically absorption and Cmax in the plasma component of 1 ng / ml, is reached in 10-20 minutes after treatment, one drop in each eye one time per day (300 mcg / day). T1 / 2 of timolol maleate from the plasma is about 6 hours. Timolol maleate actively metabolized in the liver. The metabolites, as well as a certain amount of unchanged timolol maleate is excreted in the urine.

Indications

Reducing elevated IOP in patients with open-angle glaucoma or elevated intraocular pressure in case of insufficient efficacy of other drugs for topical IOP lowering.

Contraindications

Hypersensitivity to latanoprost, timolol maleate or any other components of the drug;

COPD severe course;

sinus bradycardia;

AV blockade II-III degree;

symptomatic heart failure, cardiogenic shock;

reactive airway disease, including asthma (or indication of its presence in history).

Precautions

inflammatory, neovascular, closure or congenital glaucoma;

open-angle glaucoma in combination with psevdofakiey;

pigmentary glaucoma (due to lack of sufficient experience in the application of the drug);

aphakia, psevdoafakiya a posterior lens capsule rupture, patients with known risk factors for macular edema (latanoprost for the treatment described cases of macular edema, including cystoid in).

Pregnancy and breast-feeding

Adequate controlled studies in pregnant women have been conducted. The drug should be used during pregnancy only when the potential benefits outweigh the potential risk to the fetus.

Latanoprost and its metabolites may be released into breast milk. Timolol maleate, when used in the form of eye drops, is also found in breast milk. Given the risk of developing serious adverse reactions in infants who are breastfed, 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 Ksalakom® account the following undesirable reaction with a frequency ≥1%.

On the part of the organ of vision: blurred vision, blepharitis, cataract, conjunctivitis, lesions of the conjunctiva (the follicles, papillary reaction of the conjunctiva, petechiae, etc..), Corneal lesions (erosion, pigmentation, punctate keratitis, etc.), Refraction disorder, bloodshot eyes, eye irritation, eye pain, increased pigmentation of the iris, keratitis, photophobia, visual field loss.

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

Disorders of metabolism and nutrition: diabetes mellitus, hypercholesterolaemia.

Psychiatric disorders: depression.

From the nervous system: headache.

Vascular disorders: hypertension.

For the skin and subcutaneous tissue: hypertrichosis, rashes and skin changes (irritation dermatohalazion et al.).

On the part of the musculoskeletal system and connective tissue disorders: arthritis.

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

latanoprost

From a sight organ: eye irritation (burning sensation, feeling of sand in the eyes, itching, stinging and foreign body sensation); transient point erosion of the epithelium, eyelid edema, corneal edema and erosions; lengthening, thickening, increase in number and increased pigmentation of eyelashes and vellus hair; iritis / uveitis; macular edema, including cystoid; change of direction of growth of eyelashes sometimes cause irritation to the eyes; blurred vision.

For the skin and subcutaneous tissue: skin rash, darkening of the eyelid skin and the local skin reaction on the eyelids.

From the nervous system: dizziness.

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

On the part of the musculoskeletal system and connective tissue disorders: pain in muscles / joints.

General and local reactions: non-specific chest pain.

Timolol maleate (eye drops)

Immune system: systemic allergic reaction including anaphylaxis, angioedema, urticaria, localized and generalized rash.

Disorders of metabolism and nutrition: Anorexia, hidden symptoms of hypoglycemia in diabetic patients.

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

From the nervous system: cerebral ischemia, acute cerebrovascular accident, dizziness, increased symptoms of myasthenia gravis, paresthesia, drowsiness, fainting.

From a sight organ: cystoid macular edema, decreased corneal sensitivity; choroidal detachment following filtration surgery; ptosis, blurred vision, including changes in refraction and diplopia.

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

From the heart: arrhythmia, bradycardia, cardiac arrest, heart failure, heart block, palpitation, angina progression.

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

From the respiratory system: bronchospasm (mainly in patients with prior bronhospasticheskimi disease), cough, shortness of breath, nasal congestion, pulmonary edema and respiratory insufficiency.

On the part of the digestive tract: diarrhea, dry mouth, dyspepsia, nausea, retroperitoneal fibrosis.

For the skin and subcutaneous tissue disorders: alopecia, psevdopemfigoid, psoriasiform rash or exacerbation of psoriasis.

On the part of the musculoskeletal system and connective tissue disorders: systemic lupus erythematosus.

Reproductive system and breast: impotence, Peyronie's disease.

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

Interaction

Interaction Ksalakom® drug with other drugs has not been studied specifically.

In applying the drug Ksalakom® patients receiving beta-blocker inside, possibly a greater reduction in IOP or increased systemic manifestations of beta-blockers, so simultaneous topical application of two or more beta-blockers is not recommended.

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

With simultaneous use of timolol maleate with adrenaline sometimes developed mydriasis.

With the combination of timolol maleate with medications listed below possible additive effect with the development of systemic hypotension and / or bradycardia:

- BPC;

- Means for causing reduction of catecholamines, and beta-blockers;

- Antiarrhythmics;

- Cardiac glycosides.

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

Dosing and Administration

Adults (including elderly) - 1 drop into the affected eye (s) one time per day.

Overdose

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

latanoprost

Apart from ocular irritation and conjunctival hyperemia, and other undesirable changes in the body of an overdose are not known latanoprost.

In case of accidental admission into latanoprost should consider the following information: 1 vial with 2.5 ml solution contains 125 micrograms latanoprost. More than 90% of the drug is metabolized at the first pass through the liver. In / in infusion at a dose of 3 mg / kg in healthy volunteers did not cause any symptoms, but when the dose 5,5-10 mg / kg were observed nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. In patients with moderate bronchial asthma administering latanoprost in the eye in a dose of 7 times exceeding the therapeutic one, does not cause bronchospasm.

timolol maleate

There are cases of unintentional overdose of eye drops of timolol maleate, resulting in systemic effects were observed, similar to those in systemic administration of beta-blockers: dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. (See. "Side effects" section).

The in vitro study demonstrated that dialysis timolol easily derived from plasma or whole blood.

In patients with renal insufficiency timolol dialyzed worse.

Treatment: In case of overdose, symptomatic treatment.

special instructions

Xalacom® The drug should be used no more than once a day, as more frequent administration of latanoprost leads to a weakening of the IOP-lowering effect.

If you forget one dose, the next dose should be administered at the usual time.

If the patient simultaneously uses different eye drops, they should be applied at intervals of at least 5 minutes.

The composition includes a preparation Xalacom ® benzalkonium chloride which can be absorbed by contact lenses. Before burying drops contact lenses must be removed and re-install them after 15 minutes.

Latanoprost. It may cause a gradual increase of the brown pigment in the iris. Changing eye color due to increased melanin content in the stromal melanocytes of the iris and not to an increase in the number of melanocytes themselves. In typical cases, a brown pigmentation around the pupil appears and extends concentrically to the periphery of the iris. The entire iris or parts become brown. In most cases the color change is small and can not be established clinically. Increased pigmentation of the iris of one or both eyes is observed mainly in patients with mixed color of the iris containing a brown basis. The drug has no effect on nevi and lentigines iris; Pigment accumulation in the trabecular meshwork or not observed in the anterior chamber.

When determining the degree of pigmentation of the iris for more than 5 years did not reveal adverse effects of increased pigmentation even with continued treatment latanoprost. Patients degree of IOP reduction was similar, regardless of the presence or absence of increased pigmentation of the iris. Therefore, treatment of latanoprost can be continued in case of increased pigmentation of the iris. Such patients should be regularly monitored and, depending on the clinical situation, the treatment may be discontinued.

Increased pigmentation of the iris usually occurs within the first year after the start 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 stabilized after 5 years. In more remote terms the effects of increased iris pigmentation has not been studied. After cessation of treatment gain brown pigmentation of the iris is not mentioned, but the change in eye color may be irreversible.

In connection with the use of latanoprost described cases of skin darkening age, which may be reversible.

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

Patients applying drops only one eye may develop heterochromia.

timolol maleate

When applied topically, beta-blockers may occur such as undesirable reactions as when administered systemically. Patients with severe heart disease history should be constantly watching for timely detection of symptoms of heart failure. The local application of timolol maleate may experience the following reactions on the part of the heart and respiratory system: angina Prinzmetal progression, as well as peripheral and central circulatory disorders, hypotension, heart failure, fatal, severe reactions on the part of the respiratory system, including bronchospasm fatal in patients with asthma, bradycardia.

Before performing extensive surgery should discuss the feasibility of phasing out the beta-blockers. Drugs in this group violate the heart's ability to reflex response to beta-adrenergic stimulation, which can increase the risk of general anesthesia. There are cases of protracted severe hypotension during anesthesia, and difficulty in restoring and maintaining heart rate. During surgery, the beta-blocker effects can be eliminated by sufficient doses of adrenergic agonists.

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

Therapy Beta-blockers may mask some of the main symptoms and signs of hyperthyroidism. Abrupt discontinuation of treatment may cause a worsening of the disease.

In the treatment of beta-blockers in patients with atopy or serious anaphylactic reactions to different allergens in history may increase response when re-exposed to these allergens. In this adrenaline at normal doses that are used for the relief of anaphylactic reactions, it may be ineffective.

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

In the application of funds, lowering IOP is described choroidal detachment after filtration procedures.

Effects on ability to drive and use other mechanisms. The use of eye drops can cause a transient blurring of vision. While this effect persists, patients should not drive a car or use complex technology.

Conditions of supply of pharmacies

On prescription.

Storage conditions

In the dark place at a temperature of 2-8 ° C. Open a bottle - if t is not higher than 25 ° C, use within 4 weeks.

Keep out of the reach of children.

Shelf-life

2 years.

Do not use beyond the expiration date printed on the package.