Alatopran

Alatopran

Latanoprost, Timolol

Reduction of increased IOP in patients with open-angle glaucoma or increased ophthalmotonus with insufficient effectiveness of other drugs for topical use that reduce IOP.

Adults (including the elderly) — 1 drop in the affected eye (a) 1 time per day.

hypersensitivity to latanoprost, timolol maleate or other components of the drug,

Severe COPD,

sinus bradycardia,

AV-block of II-III degree,

clinically pronounced heart failure, cardiogenic shock,

reactive diseases of the respiratory tract, including bronchial asthma (or an indication of its presence in the anamnesis).

With caution:

inflammatory, neovascular, angle-closure, or congenital glaucoma,

open-angle glaucoma in combination with pseudophakia,

pigmented glaucoma (due to lack of sufficient experience in the use of the drug),

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

When using the drug Alatopran^® The following adverse reactions have been reported with a frequency of ≥1%.

On the part of the visual organ: visual impairment, blepharitis, cataracts, conjunctivitis, conjunctival lesions (follicles, papillary reactions of the conjunctiva, spot hemorrhages, etc.), corneal lesions (erosion, pigmentation, spot keratitis, etc.), refractive errors, eye hyperemia, eye irritation, eye pain, increased iris pigmentation, keratitis, photophobia, loss of visual fields.

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

Metabolic and nutritional disorders: diabetes mellitus, hypercholesterolemia.

Mental disorders: depression.

From the nervous system: headache.

Vascular disorders: hypertension.

From the skin and subcutaneous tissues: hypertrichosis, rash, and skin changes (irritation, dermatochalasia, etc.).

From the musculoskeletal system and connective tissue: arthritis.

The following are other adverse events that have been observed with monotherapy with individual components of the drug Alatopran^® (in addition to those mentioned above).

Latanoprost

On the part of the visual organ: eye irritation (burning sensation, feeling of sand in the eyes, itching, tingling and foreign body sensation), transient spot erosion of the epithelium, edema of the eyelids, edema and corneal erosion, elongation, thickening, increase in the number and increase in pigmentation of eyelashes and downy hair, iritis/uveitis, macular edema, including cystoid, change in the direction of eyelash growth, sometimes causing eye irritation, blurred vision.

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

From the nervous system: vertigo.

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 and connective tissue: muscle/joint pain.

General and local reactions: non-specific chest pain.

Timolol maleate (in the form of eye drops)

On the part of the immune system: systemic allergic reactions, including anaphylaxis, angioedema, urticaria, localized and generalized rash.

Metabolic and nutritional disorders: anorexia, hidden symptoms of hypoglycemia in diabetic patients.

Mental disorders: behavioral changes 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 myasthenia gravis, paresthesia, drowsiness, fainting.

On the part of the visual organ: cystoid macular edema, decreased corneal sensitivity, vascular detachment after filtration surgery, ptosis, visual disturbances, including changes in refraction and diplopia.

On the part of the organ of hearing and the vestibular apparatus: noise in the ears.

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

Vascular disorders: intermittent lameness, cold hands and feet, hypotension, 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 gastrointestinal tract: diarrhea, dry mouth, dyspepsia, nausea, retroperitoneal fibrosis.

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

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

On the part of the reproductive system and mammary glands: impotence, Peyronie's disease.

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

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

Latanoprost

In addition to eye irritation and conjunctival hyperemia, other undesirable changes on the part of the visual organ in an overdose of latanoprost are unknown.

In case of accidental ingestion of latanoprost, the following information should be taken into account: 1 bottle with 2.5 ml of the solution contains 125 mcg of latanoprost. More than 90% of the drug is metabolized at the first pass through the liver. Intravenous 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. In patients with moderate bronchial asthma, the administration of latanoprost in the eyes at a dose 7 times higher than the therapeutic dose did not cause bronchospasm.

Timolol Maleate

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

In the study in vitro It has been shown that during dialysis, timolol is easily removed from plasma or whole blood.

In patients with renal insufficiency, timolol was dialyzed worse.

Treatment: in case of overdose, symptomatic treatment is performed.

The composition of the drug Alatopran^® it contains 2 active components-latanoprost and timolol maleate. The mechanism for reducing increased intraocular pressure (IOP) in these components is different, which provides an additional reduction in IOP compared to the effect achieved when using each of these components in the form of monotherapy.

Latanoprost - analog of PGF_2α - it is a selective agonist of prostanoid FP receptors and reduces IOP by increasing the outflow of watery moisture, mainly by the uveoscleral route, as well as through the trabecular network. It was found that latanoprost does not significantly affect the production of watery moisture and the hematophthalmic barrier. During short-term treatment, latanoprost does not cause fluorescin to seep into the posterior segment of the eye in pseudophakia. When used in therapeutic doses of latanoprost has no significant pharmacological effects on the cardiovascular system and the respiratory system.

Timolol- non-selective β₁- and?₂- an adrenoblocker that does not have significant internal sympathomimetic activity-does not have a direct depressive effect on the myocardium or a local anesthetic (membrane-stabilizing) effect.

Beta-adrenoceptor blockade causes a decrease in cardiac output in healthy people and patients with heart disease. In patients with severe myocardial dysfunction, beta-blockers can inhibit the stimulating effect of the sympathetic nervous system, which is necessary for the adequate functioning of the heart.

Blockade of beta-adrenoreceptors in the bronchi and bronchioles leads to an increase in airway resistance under the influence of the parasympathetic nervous system. Such an effect can be dangerous for patients with asthma and other bronchospastic diseases (see the sections "Contraindications" and "Special instructions").

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

The exact mechanism of IOP reduction under the action of timolol maleate is not established. The results of tonography and fluorophotometry indicate that the main mechanism of action may be associated with a decrease in the formation of watery moisture. However, some studies have also shown a slight increase in outflow.

The effect of the combination of latanoprost and timolol maleate begins within an hour, and the maximum effect is observed within 6-8 hours.

With repeated use, an adequate reduction in IOP persists for 24 hours after administration.

Pharmacokinetic interaction between latanoprost and timolol maleate was not established, although 1-4 hours after the use of the combined drug, the concentration of latanoprost acid in the watery moisture was about 2 times higher than with monotherapy.

Latanoprost

Suction. Latanoprost, being a prodrug form, is absorbed through the cornea, where it is hydrolyzed to a biologically active acid. It was found that the concentration in the watery moisture reaches a maximum about 2 hours after topical application.

Distribution. V_d is (0.16±0.02) l/kg. Latanoprost acid is detected in the watery moisture during the first 4 hours, and in the plasma-only during the first hour after topical application.

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

Output. Latanoprost acid is rapidly removed from the plasma (T_1/2 =17 min). The system clearance is approximately 7 ml/min/kg. The metabolites are mainly excreted by the kidneys: after topical application, approximately 88% of the administered dose is excreted in the urine.

Timolol maleate. The concentration of timolol maleate in the watery moisture reaches a maximum about 1 h after the application of eye drops. Part of the dose is subjected to systemic absorption, and C_max in plasma, the concentration of 1 ng / ml is reached in 10-20 minutes after the use of the drug, one drop in each eye once a day (300 mcg/day). T_1/2 Timolol maleate from plasma is about 6 h. Timolol maleate is actively metabolized in the liver. The metabolites, as well as a certain amount of unchanged timolol maleate, are excreted in the urine.

• Beta-blockers in combinations
• Prostaglandins, thromboxanes, leukotrienes and their antagonists in combinations
• Ophthalmic products in combinations

Interaction of the drug Alatopran^® with other drugs, it was not specifically studied.

When using the drug Alatopran^® patients receiving beta-blockers orally may have a more pronounced decrease in IOP or an increase in the systemic manifestations of beta-blockers, so the simultaneous local use of two or more beta-blockers is not recommended.

When two PG analogues are instilled into the eyes simultaneously, a paradoxical increase in IOP is described, so the simultaneous use of two or more PG, their analogues or derivatives is not recommended.

With the simultaneous use of timolol maleate with epinephrine, mydriasis sometimes developed.

When combined with the following drugs, timolol maleate may have an additive effect with the development of systemic hypotension and / or severe bradycardia:

- BCC,

- drugs that cause a decrease in the level of catecholamines, or beta-blockers,

- antiarrhythmic drugs,

- cardiac glycosides.

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