Latassopt eye drops solution 0.05 mg/ml dropper bottle 2.5 ml

Instructions Latassopt eye drops solution 0.05 mg/ml dropper bottle 2.5 ml

Composition

active ingredient: latanoprost;

1 ml of solution contains latanoprost 0.05 mg;

excipients: sodium hydrogen phosphate, dodecahydrate; sodium dihydrogen phosphate, dihydrate; sodium chloride; benzalkonium chloride; purified water.

Dosage form

Eye drops, solution.

Main physicochemical properties: transparent colorless or almost colorless solution.

Pharmacotherapeutic group

Ophthalmic preparations. Antiglaucoma preparations and miotics. Prostaglandin analogues. ATX code S01E E01.

Pharmacological properties

Pharmacodynamics

The active substance of the drug latanoprost, a prostaglandin F2a analogue, is a selective agonist of the prostanoid FP receptor, which reduces intraocular pressure by increasing the outflow of aqueous humor. The reduction of intraocular pressure in humans begins approximately 3–4 hours after the use of latanoprost, and the maximum effect is observed after 8–12 hours. The hypotensive effect lasts for at least 24 hours.

Basic studies have shown that latanoprost is effective as monotherapy. In addition, clinical studies of the combination use of latanoprost have been conducted, which have shown that it is effective in combination with beta-blockers (timolol). Short-term (1 or 2 weeks) studies demonstrate that the effect of latanoprost is additive when used in combination with adrenergic agonists (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide) and at least partially additive when used with cholinergic agonists (pilocarpine).

Clinical studies have shown that latanoprost does not significantly affect the production of intraocular fluid. No effect of latanoprost on the blood-ophthalmic barrier was detected.

Latanoprost did not cause fluorescein leakage in the posterior segment of human pseudophakic eyes during short-term treatment.

No significant pharmacological effects of latanoprost at clinical doses on the cardiovascular and respiratory systems were detected.

Children.

The efficacy of latanoprost in pediatric patients (≤ 18 years) was demonstrated in a 12-week, double-blind, clinical trial of latanoprost versus timolol in 107 patients diagnosed with intraocular hypertension and pediatric glaucoma. In this study, the gestational age of the neonates was at least 36 weeks. Patients received 0.005% latanoprost once daily or 0.5% timolol (or optionally 0.25% for patients < 3 years of age) twice daily. The primary efficacy endpoint was the mean reduction in intraocular pressure (IOP) from baseline at week 12 of the study. The mean IOP reductions in the latanoprost and timolol groups were similar. In all age groups studied (birth to 3 years, 3 to 12 years and 12 to 18 years), the mean IOP reduction at week 12 of the study was similar in patients treated with latanoprost and patients treated with timolol. However, data on the efficacy of latanoprost in the age group of patients from birth to 3 years were obtained for only 13 patients and no significant efficacy was shown in the 4 patients who represented the age group from birth to 1 year in the clinical study. Data on use in premature newborns (born before 36 weeks of gestation) are not available.

IOP reduction rates in the subgroup of patients with primary congenital glaucoma/infantile glaucoma (PCG) were similar in patients treated with latanoprost and patients treated with timolol. Results in the non-PCG subgroup (i.e. patients with e.g. juvenile open-angle glaucoma, aphakic glaucoma) and PCG patients were similar.

The effect on IOP was evident after the first week of treatment (see table) and was maintained throughout the 12-week study, similar to that seen in adults.

Table: IOP reduction (mmHg) at week 12 of the study by active treatment group and initial diagnosis

SD – standard error.

Adjusted estimated indicator based on the analysis of covariance (ANCOVA) model.

Pharmacokinetics

Latanoprost (molecular weight 432.58) is the isopropyl ester of the active substance, i.e. a prodrug that is inactive in itself, but after hydrolysis to form latanoprost acid, it becomes biologically active.

Distribution.

Prodrugs penetrate the cornea well, and all drugs that enter the intraocular fluid are hydrolyzed while passing through the cornea.

Biotransformation and excretion.

Studies in humans have shown that the maximum concentration in the intraocular fluid is reached approximately 2 hours after topical application. Latanoprost acid is practically not metabolized in the eye. The main metabolism of latanoprost occurs in the liver. The half-life from blood plasma is 17 minutes.

Children.

An open-label study of the pharmacokinetics of latanoprost acid plasma concentrations in adult and pediatric patients (from newborns to children up to 18 years of age) with intraocular hypertension and glaucoma was conducted. Patients of all age groups were treated with 0.005% latanoprost, 1 drop in each eye for a minimum of 2 weeks. The systemic exposure to latanoprost acid was approximately twice as high in patients aged 3 to 12 years and 6 times higher in children up to 3 years of age than in adults, while maintaining a wide safety margin for latanoprost with respect to the occurrence of systemic adverse effects. The median time to reach its maximum plasma concentration was 5 minutes after a dose of latanoprost in all age groups. The median plasma half-life was short (less than 20 minutes), similar for children and adults, suggesting no accumulation of latanoprost acid in the circulation at steady state.

Indication

Reduction of elevated intraocular pressure in patients, including elderly patients, with open-angle glaucoma and elevated intraocular pressure.

Reduction of elevated intraocular pressure in pediatric patients with elevated intraocular pressure and pediatric glaucoma.

Contraindication

Hypersensitivity to the active substance or to any other components of the medicinal product.

Interaction with other medicinal products and other types of interactions

There are no comprehensive data on the interaction of latanoprost with other drugs.

Paradoxical increases in intraocular pressure have been reported following concomitant ocular administration of two prostaglandin analogues. Therefore, the concomitant use of two or more prostaglandins, prostaglandin analogues or their derivatives is not recommended.

Drug interaction studies have only been conducted in adult patients.

Application features

Latanoprost may cause a gradual change in eye color by increasing the amount of brown pigment in the iris. Patients should be informed of the possibility of permanent eye color change before treatment is initiated. Treatment of only one eye may result in permanent heterochromia.

Eye colour changes are observed mainly in patients with mixed iris colours, e.g. blue-brown, grey-brown, yellow-brown or green-brown. In studies with latanoprost, the onset of colour changes usually occurred within the first 8 months of treatment, rarely during the second or third year and was not observed after the fourth year of treatment. The progression of iris pigmentation decreases over time and stabilises after 5 years. The effect of increased pigmentation after 5 years of treatment with latanoprost has not been evaluated. In an open-label 5-year safety study with latanoprost, 33% of patients experienced increased iris pigmentation (see section 4.8). Iris colour changes are in most cases minor and often clinically unnoticeable. The incidence in patients with mixed iris colours ranged from 7% to 85%, with patients with yellow-brown irises having the highest incidence. Eye color changes were not observed in patients with uniform blue eye color and were rare in patients with uniform gray, green, or brown eye color.

In the presence of nevi or freckles on the iris, no changes were noted under the influence of treatment. In clinical studies, no accumulation of pigment was observed in the trabecular meshwork or in any other part of the anterior chamber of the eye. The results of 5 years of clinical use of latanoprost indicate that increased iris pigmentation does not cause clinical complications and its use can be continued in case of changes in iris pigmentation. However, patients should undergo regular examinations and, if the clinical situation requires it, the use of the drug should be discontinued.

Experience with latanoprost is limited in chronic angle-closure glaucoma, open-angle glaucoma in pseudophakic patients, and pigmentary glaucoma. There are currently no data on the use of latanoprost in inflammatory and neovascular glaucoma or in inflammatory eye diseases. Latanoprost has no or negligible effect on the pupil, but there are no data on its use in acute attacks of angle-closure glaucoma. Therefore, it is recommended to use the drug with caution in such conditions until more data are available.

There are limited data on the use of latanoprost in the perioperative period of cataract surgery. The drug should be used with caution in such patients.

The drug should be used with caution in patients with a history of herpetic keratitis, but its use should be avoided in cases of active keratitis caused by the herpes simplex virus and in patients with a history of recurrent herpetic keratitis, especially associated with prostaglandin analogues.

Cases of macular edema have been reported (see section 4.8), mainly in aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, and in patients with known risk factors for cystic macular edema (such as diabetic retinopathy and retinal vein occlusion). The drug should be used with caution in aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystic macular edema.

The drug can be used with caution in patients with known risk factors for the development of iritis/uveitis.

Experience with the use of latanoprost in patients with bronchial asthma is limited, although some cases of exacerbation of bronchial asthma and/or dyspnoea have been reported in the post-marketing period. Until sufficient clinical experience has been gained, the drug should be used with caution in patients with bronchial asthma (see also section "Adverse reactions").

Periorbital skin discoloration has been observed, with the majority of cases reported in patients from Japan. Currently available data suggest that periorbital skin discoloration is not permanent and in some cases has resolved with continued latanoprost treatment.

Latanoprost may gradually change the eyelashes and vulva around the eye in which it was injected and in surrounding areas; these changes include an increase in the length, thickness, pigmentation and number of hairs in the eyelashes or vulva, and the growth of eyelashes in the wrong direction. The changes in the eyelashes are reversible and disappear after stopping the drug.

The medicinal product contains benzalkonium chloride, which is often used as a preservative in ophthalmic products. There is no difference in the adverse reaction profile in children compared to adults according to the limited available data. In general, however, the ocular response to an irritant is greater in children than in adults. Irritation may lead to treatment failure in children. Benzalkonium chloride has been reported to cause eye irritation, a symptom of dry eye, and may affect the tear film and corneal surface. The medicinal product should be used with caution in patients with dry eyes and in patients who may have corneal damage. Patients should be closely monitored during prolonged use. Contact lenses may absorb benzalkonium chloride and should be removed before application of the medicinal product but may be reinserted 15 minutes later (see section 4.2).

Ability to influence reaction speed when driving vehicles or other mechanisms

Latassopt has a minor influence on the speed of reaction when driving or using other mechanisms. As with other drugs, instillation of eye drops may cause temporary blurred vision. Until this effect has passed, patients should not drive or use other mechanisms.

Use during pregnancy or breastfeeding

Pregnancy.

The safety of latanoprost in pregnant women has not been established. Its pharmacological action poses a potential risk to the course of pregnancy, to the fetus or to the newborn. Therefore, the drug should not be used during pregnancy.

Latanoprost and its metabolites may pass into breast milk, therefore, women who are breastfeeding should discontinue the use of the drug or discontinue breastfeeding.

Method of administration and doses

The medicine is intended for topical use (in the conjunctival sac).

Adults (including the elderly).

The recommended dose is 1 drop in the affected eye once a day. The optimal effect is achieved when the drug is used in the evening.

The drug should not be used more often than once a day, as it has been shown that more frequent use reduces the effectiveness of reducing intraocular pressure.

If a dose is missed, treatment should be continued by taking the next dose at the usual time.

As with any eye drops, to reduce possible systemic absorption during instillation, it is recommended to compress the lacrimal sac in the medial canthus of the eye for 1 minute (punctal occlusion). This should be done immediately after instillation of each drop.

Contact lenses should be removed before instilling eye drops; they can be put back on after 15 minutes.

When using multiple topical ophthalmic agents, the drugs should be applied at least 5 minutes apart.

Children

The drug can be used in pediatric patients at the same dosage as in adults.

Data on the efficacy and safety of the drug in the age group up to 1 year are very limited (4 patients) (see section "Pharmacological properties"). There are no available data on the use in premature infants (born before 36 weeks of gestation).

In children aged birth to 3 years, who suffer mainly from primary congenital glaucoma, surgical intervention (e.g., trabeculotomy/goniotomy) remains the first-line treatment.

The long-term safety of latanoprost in children has not been established.

Overdose

Symptoms.

Apart from eye irritation and conjunctival hyperemia, no other ocular side effects have been reported with latanoprost overdose.

Treatment.

The following information may be useful in the event of accidental ingestion of the medicinal product. One vial contains 125 mcg of latanoprost. More than 90% is metabolized during the first pass through the liver. Intravenous infusion of latanoprost at a dose of 3 mcg/kg to healthy volunteers did not cause any symptoms, but at a dose of 5.5–10 mcg/kg it caused nausea, abdominal pain, dizziness, increased fatigue, hot flashes and sweating.

When topically applied to the eyes, doses of latanoprost 7 times higher than the clinical dose were administered to patients with moderate bronchial asthma, no bronchostenosis was observed.

In case of overdose of the drug, symptomatic treatment should be carried out.

Adverse reactions

The majority of adverse events are related to the eyes. In an open-label 5-year safety study of latanoprost, 33% of patients experienced changes in iris pigmentation (see section 4.4), while other ophthalmic adverse events are usually transient and occur after administration.

Adverse reactions are categorized according to their frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000) and very rare (< 1/10000), not known (cannot be determined based on available data).

Infectious and parasitic diseases:

rarely – herpetic keratitis*§.

From the nervous system:

uncommon – headache*, dizziness*.

On the part of the organs of vision:

very common - hyperpigmentation of the iris, mild or moderate conjunctival hyperemia, eye irritation (burning sensation with a feeling of "sand in the eyes", itching, burning and sensation of a foreign body in the eye), changes in eyelashes and vellus hair of the eyelids (increase in length, thickness, pigmentation and number of eyelashes); common - punctate keratitis, mostly asymptomatic, blepharitis, eye pain, photophobia, conjunctivitis*; uncommon - eyelid edema, dry eyes, keratitis*, blurred vision, macular edema, including cystic macular edema*, uveitis*; Rare: iritis*, corneal edema*, corneal erosion, periorbital edema, trichiasis*, distichiasis, iris cyst*§, local skin reaction on the eyelids, darkening of the palpebral skin of the eyelids, ocular conjunctival pseudopemphigoid*§; very rare: periorbital changes and eyelid changes leading to deepening of the eyelid fold.

From the heart:

uncommon – angina pectoris, palpitations, very rare – unstable angina*.

From the respiratory system, chest organs and mediastinum:

uncommon – bronchial asthma*, dyspnoea*, rare – exacerbation of bronchial asthma.

Skin and subcutaneous tissue disorders:

infrequently - skin rash; rarely - itching.

Musculoskeletal and connective tissue disorders:

uncommon – myalgia*, arthralgia*.

General disorders and administration site conditions:

uncommon – chest pain*.

* Adverse reaction to latanoprost identified in the post-marketing period.

§ The frequency of adverse reactions to latanoprost was estimated using the “Rule of Three”.

Cases of corneal calcification in association with the use of phosphate-containing eye drops have been reported very rarely in some patients with significantly damaged corneas.

In two short-term clinical studies (<12 weeks) involving 93 (25 and 68) paediatric patients, the safety profile of latanoprost was similar to that in adults and no new adverse events were identified. The short-term safety profiles in the different paediatric patient subgroups were also similar (see section 5.1). Adverse events such as nasopharyngitis and fever were more common in paediatric patients than in adults.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.

Expiration date

3 years.

After opening the bottle, use the drug within 28 days.

Storage conditions

Store at 2-8°C in the original packaging and out of reach of children. After first opening, store at a temperature not exceeding 25°C.

Packaging

2.5 ml in a dropper bottle; 1 dropper bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

WORLD MEDICINE ILACH SAN. VE TIJ. A.Sh./WORLD MEDICINE ILAC SAN. VE TIC. AS

Location of the manufacturer and its business address

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey/15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.