Xalacom, eye drops 2.5ml

Composition

Eye drops in the form of a clear, colorless solution.

Auxiliary substances:

benzalkonium chloride (50% solution) – 200 mcg,

sodium hydrogen phosphate anhydrous – 2.89 mg,

sodium dihydrogen phosphate monohydrate – 6.39 mg,

sodium chloride – 4.1 mg,

water d/and – up to 1 ml of

the drugs act

by different mechanism for the reduction of elevated intraocular pressure in latanoprost and timolol combination eye drops Xalacom provide a more effective reduction of IOP in patients compared with the application of each of the active substances separately.

Latanoprost increases the outflow of watery moisture without affecting its production. Timolol reduces the formation of watery moisture in the ciliary epithelium, while not adversely affecting the work of the heart muscle.

Latanoprost easily penetrates through the cornea of the eye, concentrating as much as possible in watery moisture approximately 2 hours after instillation (with monotherapy). It is almost not metabolized in the eye tissues. The half-life of latanoprost acid is 17 minutes. Metabolites are excreted in the urine and have no pronounced biological activity.

In aqueous humor, timolol is maximally concentrated one hour after instillation of the drug (with monotherapy). Timolol is partially absorbed systemically, after 10-20 minutes manifesting in the blood plasma at a concentration of 1 ng / ml. The plasma half-life is about 6 hours. It is excreted in the urine.

After instillation of eye drops with Xalac, the concentration of latanoprost acid in aqueous humor may increase after 1-4 hours (in comparison with monotherapy).

Pharmacokinetics

No pharmacokinetic interaction was established between latanoprost and timolol maleate, although 1-4 hours after Xalacom use, the concentration of latanoprost acid in aqueous humor was approximately 2 times higher than with monotherapy.

Latanoprost

Suction

Latanoprost, being a prodrug, penetrates well through the cornea, while it is hydrolyzed to a biologically active form (acid). Cmax in aqueous humor is reached 2 hours after topical application. The systemic bioavailability of latanoprost acid after topical application of eye drops is 45%.

The distribution_of Vd is 0.16±0.02 l / kg. Latanoprost acid is detected in aqueous humor during the first 4 hours, and in blood plasma-only during the first hour after topical application. Binding to plasma proteins is 87%.

Metabolism

Latanoprost undergoes hydrolysis in the cornea of the eye under the influence of esterases to form a biologically active acid. Latanoprost acid entering the systemic circulation is mainly metabolized in the liver by beta-oxidation of fatty acids to form 1,2-dinor-and 1,2,3,4-tetranor-metabolites.

Deduction

Latanoprost acid is rapidly eliminated from the blood plasma. T_1/2 is 17 min. The plasma clearance is 0.4 l/h/kg. The systemic clearance is approximately 7 ml / min / kg. Metabolites are mainly excreted by the kidneys: after topical application, about 88% of the dose is excreted in the urine.

Timolol Maleate

Absorption

of_cmax of timolol maleate in aqueous humor is achieved after 1 h. Part of the dose is subjected to systemic absorption and 10-20 minutes after topical application of the drug,1 drop in each eye 1 time/day (300 mcg/day) in blood plasma reaches a_cmaxof 1 ng / ml.

Metabolism and elimination

Timolol maleate is actively metabolized in the liver. T_1/2 of timolol maleate from plasma is about 6 h. Metabolites, as well as some unchanged timolol maleate, are excreted by the kidneys.

Indications

Xalacom is used to reduce elevated intraocular pressure in open-angle glaucoma. It is also prescribed for increased ophthalmotonus.

Use during pregnancy and lactation

Controlled adequate studies of the use of the drug in pregnant women have not been conducted. Use is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

Latanoprost and its metabolites can be excreted in breast milk; timolol maleate has also been detected in breast milk when used as eye drops. If it is necessary to use the drug during lactation, the question of stopping breastfeeding should be decided, taking into account the risk of serious adverse reactions in newborns who are breastfed, as well as the importance of using the drug for the mother.

Use in pediatrics

The safety and efficacy of Xalacom in children has not been established.

Contraindications

• Reactive airway diseases (including bronchial asthma or an indication of its presence in the anamnesis).
• Severe COPD.
• Sinus bradycardia.
• AV blockage of II and III degrees.
• Clinically significant heart failure.
• Cardiogenic shock.
• Hypersensitivity to the components of the drug.

Use the drug with caution when: :

• Inflammatory, neovascular, angle-closure, or congenital glaucoma.
• Open-angle glaucoma in combination with pseudophakia.
• Pigmented glaucoma (due to lack of sufficient experience with the drug).
• Aphakia, pseudophakia with rupture of the posterior lens capsule.
• In patients with known risk factors for macular edema (cases of macular edema, including cystoid edema, have been described during treatment with latanoprost).

Side effects

Clinical studies have not revealed any side effects specific to Xalacom eye drops. But it is possible to develop side effects associated with the use of latanoprost and timolol.

The frequency of adverse reactions is classified as follows: very common ≥10%, often ≥1% and

From the side of the organ of vision: very often – increased pigmentation of the iris; often – visual impairment, blepharitis, cataracts, conjunctivitis, conjunctival lesions (follicles, papillary reactions of the conjunctiva, spot hemorrhages, etc. ), corneal lesions (erosion, pigmentation, keratitis, spot keratitis, etc. ), refractive errors, conjunctival hyperemia, eye irritation (including burning and itching in the eyes), eye pain, photophobia, loss of visual fields, increased tear formation.

From the endocrine system: often – diabetes mellitus.

From the side of metabolism: often-hypercholesterolemia.

Mental disorders: often-depression.

From the nervous system: often-headache.

From the side of the cardiovascular system: often-increased blood pressure.

From the skin and subcutaneous tissues: often-hypertrichosis, rash, pruritus and skin changes (irritation, dermatochalasis, etc. ).

From the musculoskeletal system: often-arthritis.

Infections and infestations: often – sinusitis, upper respiratory tract infections, and other infections.

The following are other adverse reactions that have been observed with monotherapy with individual components of Xalac® (in addition to those indicated above).

Latanoprost

From the side of the visual organ: eye irritation (burning sensation, sand sensation in the eyes, itching, tingling and foreign body sensation); transient point erosion of the corneal epithelium, eyelid edema, keratitis; lengthening, thickening, increasing the number and strengthening of pigmentation of eyelashes and downy hair; iritis/uveitis; macular edema (in patients with aphakia, in patients with pseudophakia with rupture of the posterior lens capsule or in patients with risk factors for macular edema), in including cystoid; changes in the direction of eyelash growth, sometimes causing eye irritation; blurred vision, photophobia, changes in the periorbital region and eyelids, leading to a deepening of the furrow of the upper eyelid, periorbital edema, cysts of the iris.

From the cardiovascular system: exacerbation of angina in patients with CHD, palpitation.

From the skin and subcutaneous tissues: rash, darkening of the skin of the eyelids and local skin reactions on the eyelids.

Nervous system disorders: dizziness.

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

From the musculoskeletal system: muscle pain, joint pain.

Infections and infestations: herpetic keratitis.

Other: non-specific chest pain.

Timolol (in the form of eye drops)

Allergic reactions: systemic allergic reactions, including anaphylaxis, angioedema, anaphylactic reactions, urticaria, pruritus, localized and generalized rash.

From the side of metabolism: hidden symptoms of hypoglycemia in patients with diabetes mellitus.

Mental disorders: behavioral changes and mental disorders, including confusion, hallucinations, anxiety, disorientation, nervousness, symptoms of depression, memory loss, insomnia, depression, and nightmares.

Nervous system disorders: cerebral ischemia, acute cerebral circulatory disorders, dizziness, increased symptoms of myasthenia gravis, paresthesia, drowsiness, headache, fainting.

From the side of the visual organ: cystoid macular edema, decreased corneal sensitivity; symptoms and signs of eye irritation (for example, burning sensation, itching, sand sensation in the eyes, increased lacrimation, redness), blepharitis, keratitis, blurred vision, dryness of the eye mucosa, corneal erosion, vascular detachment after filtration surgery; ptosis, visual disturbances, including refractive changes and diplopia.

From the side of the organ of hearing and vestibular apparatus: tinnitus.

From the cardiovascular system: arrhythmia, bradycardia, AV block, chronic heart failure, cardiac arrest, intracardiac conduction block, palpitation sensation, angina progression, intermittent claudication, cold hands and feet, decreased blood pressure, Raynaud’s syndrome.

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

From the digestive system: diarrhea, dry mouth, impaired taste, dyspepsia, nausea, vomiting, abdominal pain, retroperitoneal fibrosis.

From the skin and subcutaneous tissues: alopecia, pseudopemphigoid, skin rash, psoriasis-like rash or exacerbation of psoriasis.

Musculoskeletal disorders: SLE, myalgia.

From the side of the reproductive system: decreased libido, impotence, sexual dysfunction, and Peyronie’s disease.

Others: anorexia, asthenia/fatigue, chest pain, swelling.

In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.

Interaction

No special studies have been conducted on the interaction of drugs with Xalac eye drops.

If calcium channel blockers, beta-blockers, antiarrhythmic drugs (including amiodarin and quinidine), cardiac glycosides from the digitalis group, cholinomimetics, narcotic analgesics, monoamine oxidase inhibitors, and drugs that reduce the activity of catecholamines are used simultaneously with timolol, a pronounced slowing of the heart rate and a decrease in blood pressure may develop.

Topical use of two beta-blockers or two prostaglandins is not recommended.

In case of episodes of spontaneous hypoglycemia in the anamnesis, with diabetes mellitus (especially labile), with the use of insulin or drugs that reduce the level of glucose in the blood, beta-blockers should be prescribed with caution. The drug can mask the manifestations of acute hypoglycemia.

In some cases, dilation of the pupil was noted when timolol was used together with epinephrine, despite the fact that Xalacom as a monotherapy agent practically does not affect the pupil size.

How to take, course of use and dosage

Adults and the elderly are recommended to instill 1 drop 1 time a day in one or both eyes.

If one dose is missed, the next dose should be administered at the usual time.

Overdose

Latanoprost

Symptoms: in addition to eye irritation and conjunctival hyperemia, other undesirable changes on the part of the visual organ with an overdose of latanoprost are not known.

In case of accidental ingestion of latanoprost, it should be taken into account that 1 bottle with 2.5 ml of the solution contains 125 mcg of latanoprost. More than 90% of the drug is metabolized during the” first pass ” through the liver. IV infusion at a dose of 3 mcg / kg in healthy volunteers did not cause any symptoms, but when administered at a dose of 5.5-10 mcg/kg, nausea, abdominal pain, dizziness, fatigue, hot flashes and sweating were observed. These symptoms resolve within 4 hours after stopping the infusion. In patients with moderate bronchial asthma, the use of latanoprost at a dose 7 times higher than the therapeutic dose did not cause bronchospasm.

Timolol Maleate

Symptoms: cases of unintentional overdose of timolol maleate eye drops have been described, resulting in effects similar to those with systemic beta-blockers: dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest.

In vitro studies have shown that timolol maleate is readily eliminated from plasma or whole blood by dialysis. In patients with renal insufficiency, timolol maleate dialysis was worse.

Treatment: in case of overdose of Xalacom, symptomatic therapy is performed.

Special instructions

The drug should be used no more than once a day, because more frequent use leads to a weakening of the effect of reducing IOP.

If the patient is using other eye drops at the same time, they should be applied at intervals of at least 5 minutes.

Benzalkonium chloride, which is contained in Xalacom eye drops as a preservative, is adsorbed in the material from which soft contact lenses are made. Lenses should be removed before instillation of drops. You can put them back on in at least 15 minutes.

Latanoprost

Latanoprost can cause a gradual increase in the content of brown pigment in the iris. The change in eye color is caused by an increase in the number of melanin in the stromal melanocytes of the iris, and not by an increase in the number of melanocytes themselves. In typical cases, brown pigmentation appears around the pupil and extends concentrically to the periphery of the iris. In this case, the entire iris or parts of it turn brown. In most cases, the discoloration is minor and may not be detected clinically. Increased pigmentation of the iris of one or both eyes is observed mainly in patients with mixed iris color, containing brown in the base. The drug does not affect the nevi and lentigo of the iris; the accumulation of pigment in the trabecular network or anterior chamber of the eye is not noted.

When determining the pigmentation of the iris for more than 5 years, there were no undesirable consequences of increased pigmentation, even with continued therapy with latanoprost. In patients, the degree of IOP reduction was the same regardless of the degree of iris pigmentation. Therefore, treatment with latanoprost can be continued even in cases of increased iris pigmentation, but patients should be regularly monitored and, depending on the clinical situation, treatment may be discontinued.

Increased pigmentation of the iris is usually observed during the first year after the start of treatment, rarely after the second or third year. After the fourth year of treatment, this effect was not observed. The rate of pigmentation progression decreases over time and stabilizes after 5 years. In the longer term, the effects of increased iris pigmentation have not been studied. After discontinuation of treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible.

In connection with the use of latanoprost, cases of darkening of the skin of the eyelids, which can be reversible, have been described.

Latanoprost can cause gradual changes in the eyelashes and downy hair, such as lengthening, thickening, increasing pigmentation, increasing density, and changing the direction of lash growth. Changes to the eyelashes are reversible and disappear after treatment is stopped.

Patients who use drops to treat only one eye may develop heterochromia.

Timolol Maleate

Topical beta-blockers may cause the same adverse reactions as systemic beta-blockers.

Patients with a history of severe heart disease should be constantly monitored for the timely detection of symptoms of heart failure. With topical application of timolol maleate, progression of Prinzmetal angina pectoris, peripheral and central circulatory disorders, hypotension, bradycardia, fatal heart failure, severe reactions from the respiratory system (including bronchospasm with a fatal outcome in patients with bronchial asthma) may occur.

Before performing extensive surgery, the feasibility of gradual withdrawal of beta-blockers should be discussed. Drugs in this group interfere with the heart’s ability to respond to reflex beta-adrenergic stimulation, which can increase the risk of anesthesia. Cases of prolonged severe arterial hypotension during anesthesia and difficulties in restoring and maintaining cardiac activity are described. During surgery, the effects of beta-blockers can be eliminated with sufficient doses of adrenergic agonists.

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

Beta-blocker therapy can mask the symptoms of hyperthyroidism, and abrupt discontinuation of treatment can cause an exacerbation of this disease.

When treated with beta-blockers in patients with atopic or severe anaphylactic reactions to various allergens in the anamnesis, it is possible to increase the response with repeated contact with these allergens. At the same time, epinephrine (epinephrine) in the usual doses used to stop anaphylactic reactions may be ineffective.

In rare cases, timolol maleate causes increased muscle weakness in patients with Myasthenia gravis or myasthenic symptoms (for example, diplopia, ptosis, generalized weakness).

When using agents that reduce intraocular pressure, vascular detachment after filtration procedures is described.

Influence on the ability to drive vehicles and work with mechanisms

The use of eye drops may cause temporary blurred vision. Until this effect disappears, patients should not drive a car or use complex equipment.

Form of production

Xalakom. Eye drops.

Storage conditions

In a dark place, at a temperature of 2-8 °C

Shelf life

2 years

Active ingredient

Latanoprost, Timolol

Conditions of release from pharmacies

By prescription

Dosage form

eye drops