Xaloptic eye drops 50 mcg/ml bottle with dropper 2.5 ml

Instructions for use Xaloptic eye drops 50 mcg/ml bottle with a 2.5 ml dropper

Composition

active ingredient: latanoprost;

1 ml of solution contains 50 mcg of latanoprost;

Excipients: benzalkonium chloride; sodium dihydrogen phosphate, monohydrate; disodium phosphate anhydrous; sodium chloride; water for injections.

Dosage form

Eye drops, solution.

Main physicochemical properties: transparent, colorless liquid, practically free from foreign particles.

Pharmacotherapeutic group

Antiglaucoma drugs and miotics. Prostaglandin analogues.

ATX code S01E E01.

Pharmacological properties

Pharmacodynamics.

The active substance latanoprost, a prostaglandin F2α analogue, is a selective agonist of the FP prostanoid receptor, which reduces intraocular pressure (IOP) by increasing the outflow of aqueous humor. The reduction in IOP in humans begins approximately 3-4 hours after administration and reaches a maximum after 8-12 hours. The reduction in pressure is maintained for at least 24 hours.

Studies show that the primary mechanism of action is an increase in uveoscleral outflow.

During short-term treatment, latanoprost did not result in leakage of fluorescein into the posterior segment of the eye of pseudophakic patients.

It was found that in clinical doses, latanoprost does not have significant pharmacological effects on the cardiovascular and respiratory systems.

Children

The efficacy of latanoprost in pediatric patients ≤ 18 years of age 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 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 the use of the drug in premature newborns (born before 36 weeks of gestation) are not available.

IOP reduction rates in the subgroup of patients with primary congenital glaucoma (PCG)/infantile glaucoma were similar in patients treated with latanoprost and in 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 in adults.

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

SD - standard error.

†Adjusted estimate based on analysis of covariance (ANCOVA) model.

Pharmacokinetics.

Latanoprost is a prodrug in the form of an isopropyl ester, which is inactive in itself but becomes biologically active upon hydrolysis to latanoprost acid.

The prodrug is well absorbed through the cornea, and all of the drug that enters the aqueous humor is hydrolyzed during passage through the cornea.

Studies show that the maximum concentration of the drug in the aqueous humor in humans is reached approximately 2 hours after topical administration. Latanoprost acid is practically not metabolized in the eyes. The main metabolism occurs in the liver. The half-life from blood plasma in humans is 17 minutes.

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 in all age groups were treated with 0.005% latanoprost, one 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, but there was a wide safety margin for systemic adverse effects. The median time to peak plasma concentrations was 5 minutes after dosing 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 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 component of the drug.

Interaction with other medicinal products and other types of interactions

There are no comprehensive data on interactions with other drugs.

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

Latanoprost can be used concomitantly with other classes of topical ophthalmic formulations intended to lower IOP. If more than one ophthalmic drug is used topically, they should be administered at least five minutes apart.

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. Before starting treatment, patients should be warned about the possibility of permanent changes in eye color. Treatment of only one eye may result in irreversible heterochromia.

This change in eye color is observed mainly in patients with mixed iris color, i.e. blue-brown, gray-brown, yellow-brown, or green-brown eyes.

The change in colour usually begins within the first 8 months of treatment, but may occur later in a small number of patients. The progression of iris pigmentation decreases over time and stabilises after 5 years. The effect of increased pigmentation after 5 years of treatment has not been evaluated. In a 5-year safety study with latanoprost, increased iris pigmentation was reported in 33% of patients (see section 4.8). Iris colour changes are in most cases minor and often clinically unnoticeable. The incidence in patients with mixed iris colour ranged from 7% to 85%, with patients with yellow-brown iris colour having the highest incidence. Eye colour changes were not observed in patients with uniform blue eyes and were rare in patients with uniform grey, green or brown eyes.

The color change is due to an increase in melanin content in the stromal melanocytes of the iris, rather than an increase in the number of melanocytes. Typically, the brown pigmentation around the pupil spreads concentrically to the periphery of the affected eye, but the entire iris or parts of it may become even browner. No further increase in the amount of brown pigment in the iris has been observed after discontinuation of treatment.

The use of the drug did not affect nevi and freckles of the iris. No accumulation of pigment in the trabecular meshwork or elsewhere in the anterior chamber was observed. Increased pigmentation of the iris has no negative clinical consequences, and the use of latanoprost can be continued even if such pigmentation appears. However, patients should be constantly monitored and, if the clinical situation requires it, treatment with latanoprost 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 the use of the drug 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.

Latanoprost 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 oedema 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 oedema (such as diabetic retinopathy and retinal vein occlusion). Latanoprost 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 oedema.

Latanoprost should be used with caution in patients with known risk factors for iritis/uveitis.

There is no experience in patients with severe asthma, although some cases of exacerbation of asthma and/or dyspnea have been reported in the post-marketing period. Until sufficient clinical experience has been gained, the drug should be prescribed with caution to patients with asthma (see also section "Adverse reactions").

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

Latanoprost may gradually change the eyelashes and vulva around the injected eye and in surrounding areas; these changes include increased length, thickness, pigmentation, and number of hairs in the eyelashes or vulva, as well as growth of eyelashes in the wrong direction. Changes in eyelashes are reversible and disappear after stopping the drug.

Xaloptic contains benzalkonium chloride, which is often used as a preservative in ophthalmic preparations. Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. It may also cause eye irritation and discolouration of soft contact lenses. Patients with dry eyes or diseases in which the cornea is damaged should be carefully monitored during frequent or prolonged use of Xaloptic. Contact lenses may absorb benzalkonium chloride and should be removed before using Xaloptic but may be reinserted 15 minutes later (see section 4.2).

Use during pregnancy or breastfeeding

Pregnancy

The safety of this medicinal product for use 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, latanoprost should not be used during pregnancy.

Breastfeeding period

Latanoprost and its metabolites may pass into breast milk, therefore, nursing mothers should discontinue treatment with Xaloptic or discontinue breastfeeding.

Ability to influence reaction speed when driving vehicles or other mechanisms

The use of eye drops, as with other ophthalmic medications, may cause temporary blurred vision. Until this effect has passed, patients should not drive or operate machinery.

Method of administration and doses

The recommended dose for adults (including elderly patients) is 1 drop in the affected eye once daily. The optimal effect is observed when latanoprost is administered in the evening.

The dose of latanoprost should not exceed that indicated for a single administration, as more frequent administration has been shown to reduce the IOP-lowering effect.

If one dose is missed, the next dose should be administered as scheduled.

To reduce systemic absorption when administering eye drops, it is recommended to press the lacrimal sac in the middle of the canthus for one minute (nasolacrimal duct occlusion). This should be done immediately after instillation of the drops.

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

If multiple topical ophthalmic solutions are used, they should be instilled at least 5 minutes apart.

Children.

Xaloptic eye drops can be used in pediatric patients at the same dosage as for 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 the drug in children has not been established.

Overdose

Other adverse reactions, apart from eye irritation and conjunctival hyperemia, are not known in case of latanoprost overdose.

The following information may be useful in the event of accidental ingestion of Xaloptic. One vial contains 125 mcg of latanoprost. More than 90% is metabolized during the first pass through the liver. Intravenous infusion of the drug 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 increased sweating.

However, when topically applied to the eyes at doses of latanoprost 7 times higher than the clinical dose of Xaloptic, bronchostenosis was not observed in patients with moderate bronchial asthma.

In case of overdose with latanoprost, treatment should be symptomatic.

Side effects

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

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), frequency unknown (cannot be estimated from the available data).

Infectious and parasitic diseases

Rare: herpetic keratitis.

From the nervous system

Uncommon: headache, dizziness

From the organs of vision

Very common: hyperpigmentation of the iris; mild to moderate conjunctival hyperemia, eye irritation (burning sensation with a sensation of "sand in the eyes", itching, burning and foreign body sensation in the eye); changes in eyelashes and vellus hair of the eyelids (increase in length, thickness, pigmentation and number of eyelashes) (the vast majority of cases were observed in Japanese patients).

Common: punctate keratitis, mostly asymptomatic; blepharitis; eye pain; photophobia; conjunctivitis.

Uncommon: eyelid edema; dry eyes; keratitis; blurred vision; macular edema, including cystoid macular edema; uveitis.

Rare: iritis; corneal edema; corneal erosion; periorbital edema; trichiasis (eyelash growth in the wrong direction, sometimes leading to eye irritation); distichiasis (appearance of an extra row of eyelashes near the meibomian gland ducts); iris cyst; local skin reaction on the eyelids; darkening of the palpebral skin of the eyelids; ocular conjunctival pseudopemphigoid.

Very rare: periorbital and eyelid changes leading to deepening of the eyelid crease.

From the heart

Uncommon: angina pectoris; palpitations.

Very rare: unstable angina.

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchial asthma, dyspnoea.

Rare: exacerbation of bronchial asthma.

Skin and subcutaneous tissue disorders

Uncommon: skin rash.

Rare: itching.

Musculoskeletal and connective tissue disorders

Uncommon: myalgia, arthralgia.

General disorders and administration site conditions

Uncommon: chest pain.

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

From the gastrointestinal tract:

Uncommon: nausea, vomiting.

Children

In two short-term clinical studies (<12 weeks) involving 93 (25 and 68) paediatric patients, the safety profile 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). The following adverse events were observed more frequently in paediatric patients than in adults: nasopharyngitis and fever.

Expiration date

3 years.

After first opening the bottle – 4 weeks.

Storage conditions

Store in a place protected from light at a temperature of 2 to 8 °C.

Do not freeze.

After opening the bottle, the drug must be used within 4 weeks.

Store the opened bottle at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

2.5 ml in a bottle with a dropper and a cap with a guarantee ring; 1 bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

Taezhun FARM. Co. Ltd./Taejoon Pharm. Co., Ltd

Pharmaceutical Works «POLPHARMA» SA

Responsible for the release of the series:

Pharmaceutical Works «POLPHARMA» SA

Production of GLP, primary and secondary packaging, quality control and batch release:

Farmigea S.p.A.

Farmigea SpA

Location of the manufacturer and address of its place of business.

109-30, Gyeonggi-ro, Namsa-myeon, Cheoin-gu, Yongin-si, Gyeonggi-do, Korea/

109-30, Gayeongi-ro, Namsa-myeon, Heoin-gu, Yeongjin-si, Korea.

19, Pelplinska Str., 83-200 Starogard Gdanski, Poland./

19 Pelplinski Street, 83-200, Starogard Gdański, Poland.

Via Giovan Battista Oliva 6-8, Pisa, 56121, Italy

Via Giovan Battista Oliva 6-8, Pisa, 56121, Italy