Latanoprost-Optik, eye drops 0.005% 5 ml

Pharmacotherapeutic group:

Antiglaucoma agent – prostaglandin F2α analogue synthetic

ATX code:
S01EE01

Pharmacological properties

Pharmacodynamics

Latanoprost, an analogue of prostaglandin F2α, is a selective agonist of FP (prostaglandin F) receptors and decreases intraocular pressure (IOP) by increasing aqueous outflow, mainly by uveoscleral and trabecular network. IOP reduction starts about 3-4 hours after the drug is injected; the maximum effect is observed after 8-12 hours; the action lasts for at least 24 hours.

It was determined that latanoprost has no significant effect on aqueous humor production and hemato-ophthalmic barrier.

When used in therapeutic doses latanoprost has no significant pharmacological effect on cardiovascular and respiratory systems.

Pharmacokinetics

Latanoprost (molecular weight 432.58) is a prodrug esterified with isopropyl group, inactive; after hydrolysis to the acid form it becomes biologically active.

Absorption

The prodrug is well absorbed through the cornea and is completely hydrolyzed upon contact with 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, 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.

Excretion

The plasma elimination half-life is 17 minutes.

Animal studies have shown that the major metabolites (1,2-dinor- and 1,2,3,4-tetranormetabolites) have no (or low) biological activity and are excreted mainly with the urine.

Children

Latanoprost exposure is approximately 2 times greater in children aged 3 to 12 years compared to adult patients and 6 times greater in children younger than 3 years.

However, the safety profile of the drug does not differ in 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 cumulation of latanoprost acid in blood plasma.

Indications

Reduction of elevated intraocular pressure in adults and children (over 1 year of age) with open-angle glaucoma or increased ophthalmotonus.

Active ingredient

Latanoprost

Composition

The active ingredient: lathanoprost – 0.05 mg

Excipients:

• benzalkonium chloride in terms of anhydrous substance – 0.20 mg,
• sodium chloride – 4.10 mg,
• hydrous sodium hydrophosphate – 4.74 mg,
• purified water – up to 1.0 ml.

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How to take, the dosage

Topically.

Dosing regimen in adults (including elderly)

One drop in the affected eye (a) once a day. The optimal effect is achieved if the drug is used in the evening.

The drug should not be instilled more than once a day because it has been shown that more frequent instillation reduces the hypotensive effect.

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

Contact lenses must be removed before instillation and inserted not earlier than 15 minutes after instillation (see also section “Special precautions”). If other eye drops must be administered simultaneously, their administration should be separated by 5 minute intervals.

Dosing regimen in children

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

Interaction

A paradoxical increase in IOP has been described when two prostaglandin analogues are simultaneously injected into the eye, so the simultaneous use of two or more prostaglandins, their 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. Before treatment patients should be informed about a possible irreversible change in eye color.

Use of the drug on one eye may cause irreversible heterochromia. This change in eye color was mainly observed in patients with unevenly colored irises, namely: brown-blue, gray-brown, yellow-brown and green-brown.

In studies of latanoprost, darkening generally began during 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 was no evidence of 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, predominating in patients with yellow-brown irises.

No changes were observed in patients with uniformly blue-colored irises; in rare cases, changes were noted in uniformly gray, green, and brown-colored irises.

Eye color changes are due to increased melanin content in stromal iris melanocytes, rather than 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 noted after therapy has been withdrawn. According to the available clinical data the color change was not associated with any symptoms or pathological disorders.

The drug has no effect on nevi and iris lentigines. According to the results of 5-year clinical studies, accumulation of pigment in the sclerorhoidal trabecular network or other parts of the anterior chamber of the eye was not observed.

It has been shown that iris darkening does not lead to undesirable clinical consequences, so the use of latanoprost can be continued if such darkening occurs. Nevertheless, such patients should be monitored regularly and, depending on the clinical situation, treatment may be discontinued.

Experience with latanoprost in the therapy of closed-angle and congenital glaucoma, pigmentary glaucoma, and open-angle glaucoma in patients with pseudoaphakia is limited.

There is no information 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.

Due to the limited data on the use of latanoprost in the postoperative period of cataract extraction, 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.

In acute herpetic keratitis as well as in the presence of anamnestic evidence of chronic recurrent herpetic keratitis, administration of latanoprost should be avoided.
Macular edema including cystic edema has been observed during treatment with latanoprost primarily in patients with aphakia, pseudoaphakia, lens posterior 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 capsule rupture or anterior chamber intraocular lenses, or 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.

Experience with latanoprost in patients with bronchial asthma is limited, but in some cases exacerbation of asthma and/or dyspnea have been noted in the post-registration period.

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 that were reversible in some patients with continuation of latanoprost therapy.

Latanoprost may cause gradual changes in eyelashes and downy hair such as lengthening, thickening, increased pigmentation, increased density and changes in direction of eyelash growth. Eyelash changes were reversible and went away after therapy was discontinued.

Latanoprost-Optic contains benzalkonium chloride, often used as a preservative in ophthalmic medications. Benzalkonium chloride can cause eye irritation, pitting and/or toxic ulcerative keratopathy, and can also be absorbed by soft contact lenses and discolor them.

Close monitoring of patients with dry eye syndrome or other corneal diseases is required during long-term use of latanoprost. Contact lenses should be removed before the drug application and inserted again not earlier than 15 min after instillation (see also section “Dosage and administration”).

Children

The data on efficiency and safety of latanoprost usage in children under one year old is limited. There is no experience of using the drug in premature children (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 method of treatment.

Effect on the ability to drive vehicles and mechanisms
As with other ophthalmic drugs, temporary visual impairment is possible; it is not recommended to drive vehicles or operate machinery until its recovery.

Contraindications

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

Cautions

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 during treatment with latanoprost); inflammatory, neovascular glaucoma (due to insufficient 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 cataract surgery.

In this group of patients the drug should be used with caution.

Side effects

Most adverse reactions have been reported on the visual organ. In an open 5-year safety study 33% developed iris pigmentation (see section “Special Precautions”).

Other adverse reactions on the visual organ are usually transient and occur immediately after instillation. The frequency of adverse reactions was graded as follows: very common (≥1/10); common (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency is unknown (based on the available data the frequency cannot be estimated).

Infections and invasions

Frequency unknown: Herpetic keratitis.

Visual organs

Very common: iris hyperpigmentation, conjunctival hyperemia, mild to moderate eye irritation (burning sensation, feeling of sand in the eye, itching, tingling and feeling of a foreign body), changes in eyelashes (increased length, thickness, amount and pigmentation).

Often: transient pinpoint epithelial erosions (mostly asymptomatic), blepharitis, pain in the eye.

Infrequent: edema of eyelids, dry mucous membrane of the eye, keratitis, blurred vision, conjunctivitis.

Rare: iritis/veitis (mainly in predisposed patients), macular edema, eyelid edema, corneal edema, corneal erosion, periorbital edema, darkening of eyelid skin, reactions from the skin of eyelids, change of lash growth direction, thickening, darkening and lengthening of lashes, distichiasis, photophobia.

Very rarely: changes in the periorbital area and eyelash area resulting in deepening of the upper eyelid sulcus.

Frequency unknown: iris cyst, conjunctival pseudopemphigoid.

Nervous system disorders

Frequency unknown: dizziness, headache.

Heart

Infrequent: angina pectoris, palpitations.

Frequency unknown: unstable angina.

Respiratory organs

Rarely: bronchospasm (including exacerbation of the disease in patients.

Rare: bronchospasm (including exacerbation in patients with bronchial asthma in anamnesis), shortness of breath.

Skin and subcutaneous tissue

Infrequent: rash.

Rarely: skin itching.

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

Musculoskeletal and connective tissue

Frequency unknown: myalgia, arthralgia.

General disorders and local reactions

Very rare: pain in the chest.

Overdose

In addition to ocular mucosal irritation, conjunctival or episcleral hyperemia, no other adverse visual changes are known to occur with latanoprost overdose.

If latanoprost is accidentally ingested the following information should be considered: One bottle of 2.5 ml solution contains 125 mcg of latanoprost. More than 90% of the drug is metabolized during the first passage through the liver.

Intravenous infusion at a dose of 3 mcg/kg in healthy volunteers caused no symptoms, but nausea, abdominal pain, dizziness, fatigue, hot flashes, and sweating were observed when a dose of 5.5-10 mcg/kg was given. In patients with bronchial asthma of moderate severity the administration of latanoprost in the eye at a dose of 7 times therapeutic did not cause bronchospasm.

In case of overdose symptomatic treatment is performed.

Pregnancy use

Pregnancy

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

Breastfeeding period

Latanoprost and its metabolites may penetrate into breast milk. Use during breastfeeding is contraindicated. If it is necessary to take the drug, breastfeeding should be stopped.

Fertility

No effect of latanoprost on male and female fertility was found in animal studies.

Similarities

Xalatan, Xalatamax, Glauprost, Glaumax, Prolatan, Prolatan eye drops, Trilactan