Trilactan, eye drops 0.005% 2.5ml 3 pcs.

Pharmacotherapeutic group

Antiglaucoma drug – prostaglandin F2α analogue synthetic

ATX code

S01EE

Pharmacodynamics:

Latanoprost, a prostaglandin F2α analog, is a selective FP (prostaglandin F) receptor agonist and reduces intraocular pressure (IOP) by increasing aqueous humor outflow primarily by the uveoscleral route as well as through the trabecular meshwork. IOP lowering starts approximately 3-4 hours after the drug is injected; the maximum effect is observed after 8-12 hours and the action lasts for at least 24 hours.

Latanoprost has been found to have no significant effect on aqueous humor production and the blood-ophthalmic barrier.

Latanoprost has no significant pharmacological effect on the cardiovascular and respiratory systems when used in therapeutic doses. Pharmacokinetics:

Latanoprost (molecular weight 43258) is a prodrug esterified with isopropyl group is inactive; after hydrolysis to acidic form it becomes biologically active.

Intake

The prodrug is well absorbed through the cornea and is fully hydrolyzed when exposed to aqueous moisture.

Distribution

Studies in humans have shown that the maximum concentration in aqueous humor is reached 2 hours after instillation. After instillation in monkeys, latanoprost is predominantly distributed in the anterior chamber of the eye, the conjunctiva and the eyelids. Only a small amount of latanoprost reaches the posterior chamber of the eye.

Biotransformation

The active form of latanoprost is virtually unmetabolized in the eye but is biotransformed in the liver.

Elimation

The plasma elimination half-life is 17 minutes.

The animal studies have shown that the major metabolites (12-dinor- and 1234-tetranormetabolites) have no (or low) biological activity and are excreted mainly in the urine.

Children

Exposure to latanoprost is approximately 2 times higher in children aged 3 to 12 years compared to adult patients and 6 times higher in children younger than 3 years.

However, the safety profile of the drug does not differ between children and adults. The time to reach the maximum plasma concentration of latanoprost acid is 5 minutes for all age groups. The elimination half-life of latanoprost acid in children is the same as in adults. At equilibrium concentration there is no plasma cumulation of latanoprost acid.

Indications

Active ingredient

Composition

1 ml of the drug contains:

The active ingredient:

Latanoprost 0.05 mg

Excipients:

Benzalkonium chloride 0.20 mg

Sodium chloride 4.10 mg

Sodium dihydrophosphate monohydrate 4.60 mg

/p>

Sodium hydrophosphate anhydrous 4.74 mg

Injection water up to 1 ml.

How to take, the dosage

Dosing regimen in adults (including the elderly)

But one drop in the affected eye(s) once a day. The optimal effect is achieved when the drug is used in the evening.

The product should not be instilled more than once a day because more frequent instillation has been shown to decrease the hypotensive effect.

If a dose is missed, treatment continues as usual. As with any eye drops in order to decrease possible systemic effect of the drug it is recommended to press the lower lacrimal point situated at the inner corner of the eye on the lower eyelid for 1 minute immediately after instillation of each drop. This procedure should be done immediately after instillation.

Contact lenses must be removed before instillation and inserted no earlier than 15 minutes after instillation (see also section on “Special considerations”). If other eye drops are to be administered at the same time, their application should be separated by 5 minute intervals.

Dosing regimen in children

Latanoprost is used in children in the same dose as in adults. There are no data on the use of the drug in preterm infants (gestational age < 36 weeks). Data in children < 1 year old are very limited.

Principle of administration:

1. Take the stop and the vial out of the pack.

2. Open the bottle with the stop.

3 Snap the stop onto the neck of the bottle.

4. Place the stopper on the eyelid so the drip tip is in front of the eyeball to dispense the desired amount of product.

5. Remove the stopper from the neck of the bottle.

6. Close the bottle cap.

Interaction

A paradoxical increase in IOP has been described when two prostaglandin analogues or derivatives are simultaneously injected into the eye, so the simultaneous use of two or more prostaglandin analogues or derivatives is not recommended.

Pharmaceutically incompatible with eye drops containing thiomersal – precipitation.

Special Instructions

Latanoprost may gradually change eye color by increasing the brown pigment content of the iris. Patients should be informed of a possible irreversible change in eye color prior to treatment. Use of the drug in one eye may cause irreversible heterochromia. Such eye color change was mostly observed in patients with unevenly colored irises, namely: brown-blue gray-brown, yellow-brown and green-brown. In the latanoprost studies, darkening generally began within the first 8 months of treatment, rarely during the second and third years, and was not noted after four years of treatment.

The progression of iris pigmentation decreased over time and stabilized after 5 years. There were no data on increased pigmentation at 5 years. In an open 5-year safety study of latanoprost, 33% of patients developed iris pigmentation (see side effects section). In most cases, iris discoloration was insignificant and often was not clinically detectable. The incidence ranged from 7% to 85% in patients with unequal iris color, predominantly in patients with yellow-brown irises. There were no changes in patients with uniformly colored blue irises, and in rare cases changes were noted in uniformly colored green-gray and brown irises.

The change in eye color is due to an increase in melanin content in the stromal melanocytes of the iris, not an increase in the number of melanocytes themselves. In typical cases, brown pigmentation appears around the pupil and spreads concentrically to the periphery of the iris. The entire iris or its parts turn brown. No further pigmentation has been observed after withdrawal of therapy. The color change was not associated with any symptoms or pathological abnormalities, according to the clinical data available.

The drug has no effect on iris nevi and lentigos. According to the results of 5-year clinical studies, accumulation of pigment in the sclerogenic trabecular network or other parts of the anterior chamber of the eye was not observed. Iris darkening has not been shown to lead to undesirable clinical consequences, so the use of latanoprost can be continued if such darkening occurs. However, these patients should be monitored regularly, and depending on the clinical situation, treatment may be discontinued.

Latanoprost has limited experience in the therapy of closed angle and congenital pigmentary glaucoma in open angle glaucoma patients with pseudoaphakia.

There are no data on the use of latanoprost in the treatment of secondary glaucoma due to inflammatory eye disease and neovascular glaucoma.

Latanoprost has no effect on pupil size.

Because data on the use of latanoprost in the postoperative period of cataract extraction are limited, caution should be exercised when using the drug in this patient population.

Caution should be exercised when using latanoprost in patients with a history of herpetic keratitis. Patients with acute herpetic keratitis as well as those with a history of chronic recurrent herpetic keratitis should avoid the use of latanoprost.

Macular edema including cystic edema has been observed during treatment with latanoprost primarily in patients with aphakia pseudoaphakia. posterior lens capsule rupture or in patients with risk factors for cystic macular edema (particularly in diabetic retinopathy and retinal vein occlusion). Caution should be exercised when using latanoprost in patients with aphakia pseudoaphakia with posterior capsular rupture or anterior chamber intraocular lenses and in patients with known risk factors for cystic macular edema.

Caution should be exercised when using latanoprost in patients with risk factors for iritis/veitis.

The use of latanoprost in patients with bronchial asthma is limited, but in some cases in the post-registration period an aggravation of the course of asthma and/or the appearance of dyspnea have been noted. Caution should be exercised when using latanoprost in this category of patients (see also section “Side effects”). There have been cases of periorbital skin darkening, which in some patients were reversible with continuation of therapy with latanoprost.

Latanoprost can cause gradual changes to eyelashes and downy hair such as lengthening, thickening, increasing pigmentation, increasing density and changing the direction of eyelash growth. Eyelash changes were reversible and went away after discontinuation of therapy.

Trilactan® contains benzalkonium chloride, often used as a preservative in ophthalmic medications. Benzalkonium chloride may cause ocular irritation pitting keratopathy and/or toxic ulcerative keratopathy and may be absorbed by soft contact lenses and discolor them. Close monitoring of patients with dry eye syndrome or other corneal conditions is required during long-term use of latanoprost. Contact lenses should be removed before using the drug and inserted again not earlier than 15 minutes after instillation (see also section “Dosage and administration”).

In children

There is limited information on the efficacy and safety of latanoprost in children younger than one year of age. There is no experience of using the drug in premature infants (gestational age less than 36 weeks).

There are no data on the safety of long-term use of latanoprost in children. In primary congenital glaucoma in children from 0 to 3 years old, surgical intervention (goniotomy/trabeculotomy) remains the standard treatment.

As with other ophthalmic drugs, temporary visual impairment may occur; until recovery, driving or operating machinery is not recommended.

Contraindications

High sensitivity to latanoprost or other components of the drug. Age under 1 year (efficacy and safety have not been established).

Aphakia pseudoaphakia with rupture of the posterior lens capsule; patients with risk factors for macular edema (cases of macular edema including cystoid edema have been described with treatment with latanoprost); inflammatory neovascular glaucoma (due to lack of sufficient experience with the drug); bronchial asthma; history of herpetic keratitis.

The drug should be avoided in patients with an active form of herpetic keratitis and recurrent herpetic keratitis especially associated with taking prostaglandin F2α analogues. The drug should be used with caution in patients with risk factors for iritis/veitis. There are limited data on the use of the drug in patients scheduled for surgical intervention for cataract. In this connection the drug should be used with caution in this group of patients.

Side effects

The majority of adverse reactions have been reported in the visual organ. In an open 5-year safety study, 33% developed iris pigmentation (see section “Special Precautions”). Other visual adverse reactions are usually transient and occur immediately after instillation. Grading of adverse reactions by frequency of occurrence was performed as follows: very common (≥1/10); common (≥1/100 < 1/10); infrequent (≥1/1000 < 1/100); rare (≥1/10 000 < 1/1000); very rare (< 1/10 000); frequency is unknown (based on available data the frequency cannot be estimated).

Infections and invasions

Frequency unknown: herpetic keratitis.

Visually transmitted disorders

Very common: iris hyperpigmentation conjunctival hyperemia Eye irritation of mild to moderate degree (burning sensation of sand in the eyes itching tingling and feeling of foreign body) changes in eyelashes (increased thickness of the number and pigmentation).

Often: transient pitting erosions of the epithelium (mostly asymptomatic) blepharitis pain in the eye.

Infrequent: swelling of the eyelids dryness of the mucous membrane of the eye keratitis blurred vision conjunctivitis.

Rarely: iritis/veitis (mainly in predisposed patients) macular edema eyelid edema corneal erosion corneal periorbital edema darkening of eyelid skin reactions changes in the direction of eyelash growth thickening darkening and lengthening of eyelashes distichiasis photophobia.

Very rare: changes in the periorbital area and in the area of the eyelashes resulting in deepening of the sulcus of the upper eyelid.

Prevalence unknown: iris cyst pseudopemphigoid of the conjunctiva.

Nervous system disorders

Prevalence unknown: dizziness headache.

Heart side

Infrequent: angina pectoris palpitations.

Prevalence unknown: unstable angina pectoris.

Respiratory disorders

Rarely: bronchospasm (including exacerbation in patients with a history of bronchial asthma) dyspnea.

Skin and subcutaneous tissue disorders

Infrequent: rash.

Rarely: skin itching.

Very rare: darkening of the eyelid skin and local skin reactions on the eyelids.

Musculoskeletal and connective tissue disorders

Prevalence unknown: myalgia arthralgia.

General disorders and local reactions

Very rare: chest pain.

Overdose

In addition to ocular mucosal irritation, conjunctival hyperemia or episclera are not known to cause other adverse visual changes in latanoprost overdose.

In case of accidental oral administration of latanoprost, the following information should be considered: One bottle with 25 ml of solution contains 125 mcg of latanoprost. More than 90% of the drug is metabolized on first passage through the liver. Intravenous infusion at a dose of 3 mcg/kg in healthy volunteers did not cause any symptoms; however, when a dose of 55-10 mcg/kg was administered, nausea, abdominal pain, dizziness, fatigue, hot flashes and sweating were observed. In patients with bronchial asthma of moderate severity, administration of latanoprost in the eye at a dose of 7 times the therapeutic dose did not cause bronchospasm.

In case of overdose symptomatic treatment is carried out.

Pregnancy use

Pregnancy

The safety of latanoprost during pregnancy in humans has not been established. Latanoprost may have toxic effects on the fetus and the newborn. Use during pregnancy is contraindicated.

Breast-feeding period

Latanoprost and its metabolites may penetrate into breast milk. Use during breastfeeding is contraindicated. Breast-feeding should be stopped if it is necessary to use the drug.

Fertility

The effects of latanoprost on male and female fertility have not been found in animal studies.

Similarities