Prolatan eye drops 0.005% bottle 2.5 ml No. 3

Instructions Prolatan eye drops 0.005% bottle 2.5 ml No. 3

Composition

active ingredient: latanoprost;

1 ml of solution contains 0.05 mg of latanoprost;

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

Dosage form

Eye drops.

Main physicochemical properties: transparent colorless solution.

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 prostanoid FP receptor, which reduces intraocular pressure by increasing the outflow of aqueous humor. The reduction in intraocular pressure in humans begins approximately 3-4 hours after administration of the drug, 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 combination use of the drug have been conducted. These included studies that demonstrated the efficacy of latanoprost when used in combination with beta-blockers (timolol). Short-term (1-2 weeks) studies show that the effect of latanoprost is additive when used in combination with adrenergic agonists (epinephrine dipivalyl), oral carbonic anhydrase inhibitors (acetazolamide) and at least partially additive when used with cholinergic agonists (pilocarpine).

Clinical studies have shown that latanoprost has no statistically significant effect on aqueous humor production. No effect of latanoprost on the blood-ophthalmic barrier has been found.

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 of age was demonstrated in a 12-week, double-blind clinical trial comparing it to 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 in adults.

Table 1.

SD - standard error.

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

Pharmacokinetics

Prodrugs penetrate the cornea well, and all of them that enter the intraocular fluid are hydrolyzed during passage through the cornea.

Studies in humans have shown that the maximum concentration in the intraocular fluid is reached approximately 2 hours after topical administration. There is virtually no metabolism of lanotanoprost acid in the eye. The main metabolism of the drug occurs in the liver. In humans, the plasma half-life 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 in all age groups were treated with 0.005% latanoprost 1 drop in each eye for at least 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 a wide safety margin for systemic adverse effects was maintained. 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 in children and adults, suggesting no accumulation of latanoprost acid in the circulation at steady state.

Indication

Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma and elevated intraocular pressure.

Reducing elevated intraocular pressure in children with elevated intraocular pressure and pediatric glaucoma.

Contraindication

Known hypersensitivity to any of the components of the drug.

Interaction with other medicinal products and other types of interactions

There are no comprehensive data on the interaction of the drug with other medicines.

Paradoxical increases in intraocular pressure 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.

Drug interaction studies have only been conducted in adult patients.

Application features

The drug may cause a gradual change in eye color by increasing the amount of brown pigment in the iris. Before starting treatment, patients should be informed of the possibility of permanent eye color change. Treatment of only one eye may result in permanent heterochromia.

Eye colour changes are observed mainly in patients with mixed iris colours, such as 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 the drug has not been evaluated. In an open-label 5-year safety study with latanoprost, 33% of patients were reported to have 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.

The color change is due to an increase in melanin content in the stromal melanocytes of the iris, and not to an increase in the number of melanocytes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the affected eye, but the entire iris or parts of it may become more brown. After discontinuation of treatment, no further increase in brown pigmentation of the iris has been observed. To date, there is no evidence in clinical studies that this phenomenon is associated with any symptoms or pathological changes.

Experience with latanoprost in chronic angle-closure glaucoma, open-angle glaucoma in patients with pseudophakia, and pigmentary glaucoma is limited. There are currently no data on the use of the drug in inflammatory and neovascular glaucoma or in inflammatory eye diseases. The drug 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.

There are limited data on the use of the drug in the perioperative period for 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 in patients with bronchial asthma is limited, although some cases of exacerbation of bronchial 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 bronchial 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.

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 discontinuation of the drug.

The product contains benzalkonium chloride, which is often used as a preservative in ophthalmic products. 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. With frequent or prolonged use of the product, patients with dry eyes or diseases in which the cornea is damaged should be carefully monitored. Contact lenses may absorb benzalkonium chloride, so they should be removed before using the product, but can be reinserted 15 minutes later (see section "Method of administration and dosage").

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 newborn. Therefore, the drug should not be used during pregnancy.

Breast-feeding.

Latanoprost and its metabolites may pass into breast milk, so women who are breastfeeding should stop breastfeeding before treatment with this drug.

Reproductive function (fertility).

Latanoprost, according to animal studies, does not affect male or female fertility.

Women planning a pregnancy.

The physician should be informed immediately if the patient plans to become pregnant or thinks she is pregnant and is using latanoprost 0.005% eye drops, solution. The drug should be used in women of childbearing age only under the supervision of a physician.

Contraception in men and women.

Data is missing.

Ability to influence reaction speed when driving vehicles or other mechanisms

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

Method of administration and doses

Recommended dose for adults, including the elderly

Recommended therapy: 1 drop in the affected eye once a day. The optimal effect is achieved when the drug is used in the evening.

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 press the lacrimal sac in the medial canthus of the eye for 1 minute (punctal occlusion). This should be done each time, immediately after instillation.

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

When using multiple topical ophthalmic agents other than latanoprost, they should be applied at least 5 minutes apart.

Children.

The drug can be used in pediatric patients with 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 safety of long-term use in children has not been established.

Overdose

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

The following information may be useful in the event of accidental ingestion. 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 sweating.

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

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

Adverse reactions

The majority of adverse events are related to the visual system. 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 only with the use of the drug.

Infectious and parasitic diseases: herpetic keratitis.

Nervous system disorders: headache, dizziness.

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

Cardiac disorders: palpitations, angina pectoris, including unstable angina.

Respiratory, thoracic and mediastinal disorders: wheezing, exacerbation of bronchial asthma and dyspnoea.

Skin and subcutaneous tissue disorders: skin rash, itching.

Musculoskeletal and connective tissue disorders: myalgia; arthralgia.

General disorders and administration site conditions: chest pain.

There have been isolated reports of corneal calcification in patients who have had significant corneal damage associated with the use of phosphate-containing eye drops.

Side effects in children

The safety profiles in the different paediatric subgroups studied were similar to those in adults. Adverse reactions observed more frequently in children than in adults were nasopharyngitis and pyrexia.

Reporting of suspected adverse reactions

Once a medicinal product has been authorised, reporting of suspected adverse reactions is an important procedure. This allows monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals can report all suspected adverse reactions via the national reporting system.

Patients, in case of undesirable manifestations, adverse reactions or in case of lack of therapeutic effect, can inform the Contact Person of the company "Sentiss Pharma Private Limited", India in Ukraine by phone: +38044 585-04-60 or by e-mail: info@regata.in.ua.

Expiration date

2 years.

Storage conditions

Store at 2 – 8 °C, protected from light.

After opening the bottle, store for no more than 4 weeks at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

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

Vacation category

According to the recipe.

Producer

SENTISS PHARMA PVT. LTD., India/

SENTISS PHARMA PVT. LTD., India.

Address

Village Khera Nihla, Tehsil Nalagarh, Distt. Solan, Himachal Pradesh, 174 101 India/

Village Khera Nihla, Tehsil Nalagarh, Distt. Solan, Himachal Pradesh, 174 101, India.

Applicant

SENTISS PHARMA PVT. LTD., India/

SENTISS PHARMA PVT. LTD., India.

Applicant's location

212/D-1, Ashirwad Commercial Complex, Green Park, New Delhi, 110016, India/

212/D-1, Ashirwad Commercial Complex, Green Park, New Delhi, 110016, India.