Structure
Active ingredient: Latanoprost 0,05 mg
Excipients:
Benzalkonium chloride 0.20 mg
Sodium chloride 4.10 mg
Sodium dihydrogen phosphate monohydrate 4.60 mg
Sodium hydrogen phosphate anhydrous 4.74 mg
Water for injection up to 1 ml
Pharmacodynamics:
Latanoprost - an analogue of prostaglandin F2? - is a selective agonist of FP receptors (prostaglandin F) and reduces intraocular pressure (IOP) by increasing the outflow of aqueous humor, mainly by the uveoscleral route, as well as through the trabecular network. IOP reduction begins approximately 3-4 hours after drug administration, the maximum effect is observed after 8-12 hours, the effect persists for at least 24 hours. It was established that latanoprost does not significantly affect the production of aqueous humor and the blood-brain barrier. When used in therapeutic doses, latanoprost does not have a significant pharmacological effect on the cardiovascular and respiratory systems.
Indications:
Reducing increased intraocular pressure in adults and children (over the age of 1 year) with open-angle glaucoma or increased ophthalmotonus.
Pharmacokinetics:
Latanoprost (molecular weight 432.58) is a prodrug esterified with an isopropyl group, inactive; after hydrolysis to an acid form, it becomes biologically active. Absorption The prodrug is well absorbed through the cornea and is completely hydrolyzed when it enters aqueous humor. Distribution Studies in humans have shown that the maximum concentration in aqueous humor is reached 2 hours after instillation. After instillation to monkeys, latanoprost is distributed mainly in the anterior chamber of the eye, conjunctiva and eyelids.
Only a small amount of latanoprost reaches the posterior chamber of the eye. Biotransformation The active form of latanoprost is practically not metabolized in the eye, but undergoes biotransformation in the liver. Withdrawal The plasma half-life is 17 minutes. Animal studies have shown that the main metabolites (1,2-dinore and 1,2,3,4-tetranoromethabolites) do not (or have low) biological activity and are excreted mainly in urine. Children Exposure to latanoprost is approximately 2 times higher in children aged 3 to 12 years compared with adult patients and 6 times higher in children under 3 years of age. However, the safety profile of the drug is not different in children and adults. The time to reach the maximum concentration of latanoprost acid in the blood plasma is 5 minutes for all age groups. The half-life of latanoprost acid in children is the same as in adults. In equilibrium concentration, no latanoprost acid in the blood plasma is cumulated.
Side effects:
Most adverse reactions were noted by the organ of vision. In an open 5-year safety study, 33% developed iris pigmentation (see Special Instructions). Other adverse reactions from the organ of vision, as a rule, are transient and are noted immediately after instillation. The frequency of adverse reactions was graded as follows: very often (> 1/10); often (greater than or equal to 1/100, <1/10); infrequently (greater than or equal to 1/1000, <1/100); rarely (greater than or equal to 1/10 000, <1/1000); very rarely (<1/10 000); the frequency is unknown (based on the available data, the frequency cannot be estimated). Infections and infestations Frequency unknown: herpetic keratitis.
On the part of the organ of vision Very often: hyperpigmentation of the iris, conjunctival hyperemia, mild to moderate eye irritation (burning sensation, sand sensation in the eyes, itching, tingling and foreign body sensation), eyelash changes (increase in length, thickness, amount and pigmentation).
Often: transient pinpoint erosion of the epithelium (mostly asymptomatic), blepharitis, eye pain. Infrequently: edema of the eyelids, dryness of the mucous membrane of the eye, keratitis, blurred vision, conjunctivitis. Rarely: iritis / uveitis (mainly in predisposed patients), macular edema, eyelid edema, corneal edema, corneal erosion, periorbital edema, eyelid skin darkening, eyelid skin reaction, change in eyelash growth direction, thickening, darkening and lengthening of eyelashes, dichyiasis photophobia. Very rarely: changes in the periorbital region and in the eyelash region, leading to a deepening of the furrow of the upper eyelid. Frequency unknown: iris cyst, conjunctival pseudopemphigoid. From the nervous system. Frequency unknown: dizziness, headache. From the side of the heart Infrequently: angina pectoris, palpitations. Frequency unknown: unstable angina pectoris. On the part of the respiratory system Rarely: bronchospasm (including exacerbation of the disease in patients with a history of bronchial asthma), shortness of breath. On the part of the skin and subcutaneous tissue Infrequently: rash. Rarely: skin itching. Very rare: darkening of the skin of the eyelids and local skin reactions on the eyelids. From the musculoskeletal system and connective tissue Frequency unknown: myalgia, arthralgia. General disorders and local reactions Very rarely: chest pain.
Special storage conditions
Store the opened bottle at a temperature not exceeding 25 ° C. After opening the bottle - 1 month.
Special conditions:
Latanoprost can gradually change eye color by increasing the brown pigment content in the iris. Before starting treatment, patients should be informed of a possible irreversible change in eye color. The use of a drug in one eye can cause irreversible heterochromia. Such a change in eye color was mainly observed in patients with unevenly colored irises, namely, blue-brown, gray-brown, yellow-brown and green-brown. In studies of latanoprost, darkening usually began during the first 8 months of treatment, rarely during the second and third years, and was not observed after four years of treatment. The progression of iris pigmentation decreased over time and stabilized after 5 years.
Data on increased pigmentation over 5 years are not available. In an open 5-year study of latanoprost safety, 33% of patients developed iris pigmentation (see the section “Side effects”). In most cases the color change of the iris was insignificant and often was not clinically detected. The frequency of occurrence ranged from 7 to 85% in patients with unequal irises, prevailing in patients with yellow-brown irises. Changes in patients with uniformly colored blue irises were not observed, in rare cases, changes were noted with uniformly colored irises of gray, green and hazel.
The change in eye color is due to an increase in the melanin content in the stromal melanocytes of the iris, and not an increase in the number of melanocytes themselves. In typical cases brown pigmentation appears around the pupil and concentrically extends to the periphery of the iris. In this case, the entire iris or parts thereof acquire a brown color. After discontinuation of therapy, further pigmentation was not observed. According to available clinical data, the color change was not associated with any symptoms or pathological disorders. The drug does not affect the nevus and lentigo of the iris.
According to the results of 5-year clinical studies, pigment accumulation in the sclero-corneal trabecular network or other parts of the anterior chamber of the eye was not noted. It was shown that darkening of the iris does not lead to undesirable clinical consequences, therefore, the use of latanoprost with the occurrence of such darkening can be continued. However, such patients should be monitored regularly and, depending on the clinical situation, treatment may be discontinued. The experience of using latanoprost in the treatment of angle-closure and congenital glaucoma, pigmentary glaucoma, open-angle glaucoma in patients with pseudo-aphakia is limited. There is no information on the use of latanoprost in the treatment of secondary glaucoma due to inflammatory eye diseases and neovascular glaucoma. Latanoprost does not affect the size of the pupil.
Due to the fact that information on the use of latanoprost in the postoperative period of cataract extraction is limited, caution should be exercised when using the drug in this category of patients. Caution should be exercised when using a history of latanoprost in patients with herpetic keratitis. In acute herpetic keratitis, as well as in the presence of anamnestic information about chronic recurrent herpetic keratitis, it is necessary to avoid the appointment of latanoprost. Macular edema, including cystic edema, was observed during latanoprost therapy mainly in patients with aphakia, pseudo-aphakia, rupture of the posterior lens capsule , or in patients with risk factors for cystic macular edema (in particular, with diabetic retinopathy and retinal vein occlusion). Caution should be exercised when using latanoprost in patients with aphakia, pseudo-aphakia with rupture of the posterior capsule or anterior chamber intraocular lenses, as well as in patients with known risk factors for cystic edema of the macula.
Caution should be exercised when using latanoprost in patients with risk factors for the development of iritis / uveitis. The experience of using latanoprost in patients with bronchial asthma is limited, but in some cases in the post-registration period, an exacerbation of the course of asthma and / or the appearance of shortness of breath was noted . Caution should be exercised when using latanoprost in this category of patients (see also the section “Side effects”).
Cases of darkening of the skin of the periorbital region were noted , which in a number of patients were reversible with continued therapy with latanoprost. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Changes in eyelashes were reversible and passed after the cessation of therapy. Trilaktan® contains benzalkonium chloride, often used as a preservative in ophthalmic drugs. Benzalkonium chloride can cause eye irritation, pinpoint keratopathy and / or toxic ulcerative keratopathy, as well as be absorbed by soft contact lenses and discolor them.
Careful monitoring of the condition of patients with dry eye syndrome or other diseases of the cornea is required with prolonged use of latanoprost. Before using the drug, it is necessary to remove contact lenses and reinstall them no earlier than 15 minutes after instillation (see also the section “Dosage and administration”). Children Information on the efficacy and safety of latanoprost in children younger than one year is limited.
There is no experience with the use of the drug in premature infants (gestational age less than 36 weeks). There is no information on the safety of the long-term use of latanoprost in children. In primary congenital glaucoma in children from 0 to 3 years, surgical intervention (goniotomy / trabeculotomy) remains the standard treatment method. Effect on the ability to drive vehicles and mechanisms As with other ophthalmic drugs, temporary visual impairment is possible; prior to its restoration it is not recommended to drive vehicles or work with mechanisms.
Contraindications:
Hypersensitivity to latanoprost or other components of the drug. Age up to 1 year (efficacy and safety not established). With caution Afakia, pseudo-aphakia with rupture of the posterior lens capsule; patients with risk factors for macular edema (in the treatment of latanoprost, cases of the development of macular edema, including cystoid edema, have been described ); inflammatory, neovascular glaucoma (due to lack of sufficient experience with the use of the drug); bronchial asthma; a history of herpetic keratitis. Avoid the use of the drug in patients with an active form of herpetic keratitis and recurrent herpetic keratitis, especially associated with the administration of prostaglandin F2 alpha analogues. The drug should be used with caution in patients with risk factors for the development of iritis / uveitis. There is limited data on the use of the drug in patients who are planning surgery for cataracts. In this regard, in this group of patients, the drug must be used with caution. Pregnancy and lactation Pregnancy The safety of latanoprost during pregnancy in humans has not been established. Latanoprost may have toxic effects on pregnancy, the fetus, and the newborn. Use during pregnancy is contraindicated. Breastfeeding Latanoprost and its metabolites may pass into breast milk. Use during breastfeeding is contraindicated. If it is necessary to use the drug, breastfeeding must be stopped. Fertility No effects of latanoprost on male and female fertility have been found in animal studies.
Drug interaction:
With the simultaneous instillation of two prostaglandin analogs into the eyes, a paradoxical increase in IOP is described, therefore the simultaneous use of two or more prostaglandins, their analogues or derivatives is not recommended. Pharmaceutically incompatible with eye drops containing thiomersal - precipitation.
Dosage:
Dosage regimen in adults (including the elderly) One drop per affected eye (a) once a day. The optimal effect is achieved when using the drug in the evening. You should not instill the drug more than 1 time per day, since it is shown that more frequent administration reduces the hypotensive effect. If you skip one dose, treatment is continued according to the usual scheme. As with any eye drops, in order to reduce the possible systemic effect of the drug, immediately after the instillation of each drop it is recommended to press for 1 minute on the lower lacrimal opening located at the inner corner of the eye on the lower eyelid. This procedure must be performed immediately after installation. Before instillation, it is necessary to remove contact lenses and install them no earlier than 15 minutes after administration (see also the section “Special Instructions”). If you need to use other eye drops at the same time, their use should be distinguished by a 5-minute interval. Dosage regimen in children Latanoprost is used in children in the same dose as in adults. Data on the use of the drug in premature infants (gestational age <36 weeks) are not available. Data in children <1 year of age are very limited.
Overdose:
In addition to irritation of the mucous membrane of the eyes, conjunctival hyperemia or episclera, other undesirable changes in the organ of vision in case of an overdose of latanoprost are not known. In case of accidental ingestion of latanoprost, the following information should be considered: one bottle with 2.5 ml of solution contains 125 μg of latanoprost. More than 90% of the drug is metabolized during the first passage through the liver. Intravenous infusion at a dose of 3 μg / kg in healthy volunteers did not cause any symptoms, however, with a dose of 5.5-10 μg / kg, nausea, abdominal pain, dizziness, fatigue, hot flashes and sweating were observed. In patients with moderate bronchial asthma, the introduction of latanoprost into the eyes at a dose 7 times higher than the therapeutic did not cause bronchospasm. In case of an overdose, symptomatic treatment is performed.
