Taflopress Rompharm eye drops 0.015mg/ml vials, 2.5ml

Composition

Composition per 1 ml of the drug:

Active ingredient: tafluprost-0.0150 mg;

excipients: disodium edetate-0.50 mg, glycerol-18.00 mg, boric acid-5.00 mg, tyloxapol-1.50 mg, polyquaternium-1-0.01 mg,1 M solution of hydrochloric acid or 1 M solution of sodium hydroxide-up to pH 6.0 ± 0.1, purified water – up to 1.00 ml

Pharmacological action

Pharmacotherapy group: Anti – glaucoma agent-prostaglandin F2-alpha synthetic analog.

ATX Code: S01EE05

Pharmacological properties

Pharmacodynamics

Tafluprost is a fluorinated analog_{of prostaglandin f2a}. Tafluprost acid, a biologically active metabolite of tafluprost, is highly active and selective against the human prostanoid FP receptor. The affinity of tafluprost acid for the FP receptor is 12 times higher than that of latanoprost. Pharmacodynamic studies in monkeys have shown that tafluprost reduces intraocular pressure (IOP) by increasing the uveoscleral outflow of aqueous humor.

Experiments on monkeys with normal and elevated IOP have shown that tafluprost is an effective drug for reducing IOP. In a study examining the IOP-lowering effect of tafluprost metabolites, it was found that only tafluprost acid significantly reduced IOP.

A study in rabbits showed that when tafluprost was applied as 0.0015% eye drops once a day for 4 weeks, blood flow in the optic nerve disc increased significantly (by 15%) compared to the initial value measured on days 14 and 28 using laser speckle flowography.

Clinical efficacy

Reduction of IOP begins 2-4 hours after the first instillation of tafluprost, and the maximum effect is achieved after about 12 hours. The duration of the effect persists for at least 24 hours. In a 6-month study, tafluprost showed a significant effect of reducing IOP at different time points from 6 to 8 mm Hg compared to latanoprost, which reduces IOP by 7-9 mm Hg. In another 6-month clinical study, tafluprost reduced IOP by 5-7 mm Hg compared to timolol, which reduces IOP by 4-6 mm Hg. The effect of reducing IOP of tafluprost also persisted with increasing the duration of these studies up to 12 months.

In a 6-week study, the effect of reducing IOP of tafluprost was compared with its indifferent filler when used with timolol. Compared to baseline values after a 4-week course of timolol use, the additional effect of reducing IOP was 5-6 mm Hg in the timolol-tafluprost group and 3-4 mm Hg in the timolol-indifferent filler group. In a small cross-sectional study with a 4-week treatment period, tafluprost dosage formulas with or without preservative showed a similar effect in reducing IOP-more than 5 mmHg.

In a 3-month study in the United States, when comparing the drug formula of tafluprost without preservative with timolol (also without preservative), it was found that tafluprost reduced IOP by 6.2-7.4 mmHg at different time points, while the values for timolol varied between 5.3 and 7.5 mmHg.

Absorption rate

After instillation of tafluprost,0.0015% eye drops, once a day, one drop in both eyes for 8 days, tafluprost acid concentrations in blood plasma were low and had a similar profile on days 1 and 8. The maximum concentration in blood plasma (cmax) was reached 10 minutes after instillation and decreased below the lower detection limit (10 pg/ml) less than 1 hour after use of the drug. Mean values of_cmax (24.4 and 31.4 pg / ml) and AUC_0-last (405.9 and 581.1 pg*min/ml) were almost identical on days 1 and 8, indicating that a stable tafluprost concentration was achieved during the first week of treatment. No statistically significant differences in systemic bioavailability were found between the preservative-free and non-preservative formulations.

In a rabbit study, the absorption of tafluprost in aqueous humor was comparable after a single instillation of tafluprost,0.0015% eye drops, with or without preservative.

Distribution

The monkey study did not reveal a specific distribution of radioactively labeled tafluprost in the iris, ciliary body, or vasculature of the eye, including the retinal pigment epithelium, which indicates a low affinity of tafluprost for the melanin pigment. In an autoradiographic study in rats, the highest concentration of radioactivity was observed in the cornea, followed by the eyelids, sclera, and iris. Systemically, radioactivity was distributed to the lacrimal apparatus, palate, esophagus, gastrointestinal tract, kidneys, liver, gallbladder, and bladder.

The binding of tafluprost acid to human serum albuminin vitro was 99% for 500 ng / ml of tafluprost acid.

Metabolism

In vitro studies have shown that the main route of tafluprost metabolism in humans is hydrolysis to form a pharmacologically active metabolite, tafluprost acid, which is further metabolized by glucuronidation or beta-oxidation. Beta-oxidation products,1,2-dinor and 1,2,3,4-tetranor of tafluprost acid, which are pharmacologically inactive, can be glucuronated or hydroxylated. The cytochrome P450 (CYP) enzyme system is not involved in tafluprost acid metabolism. In a study conducted on rabbit cornea tissue, it was found that the main esterase responsible for the essential hydrolysis of tafluprost to tafluprost acid is carboxylesterase. Butyrylcholinesterase, but not acetylcholinesterase, can also promote hydrolysis.

Deduction

In a rat study, after a single instillation of 3H-tafluprost (0.005% eye drops; 5 µl/eye) in both eyes for 21 days, about 87% of the total radioactive dose was detected in the excrement. Approximately 27-38% of the total dose was excreted by the kidneys, and approximately 44-58% of the dose was excreted through the intestines.

Indications

Increased intraocular pressure in patients with open-angle glaucoma and ophthalmohypertension:

– as monotherapy in patients with insufficient response to first-line drugs or in the presence of intolerance to first-line drugs or contraindications to these drugs;

– as an adjunct therapy to beta-blockers.

Use during pregnancy and lactation

Pregnancy

There are no data on the use of tafluprost in pregnant women. Tafluprost may have adverse pharmacological effects on the course of pregnancy and/or on the fetus / newborn. Animal studies have revealed reproductive toxicity. Therefore, tafluprost should not be used during pregnancy unless there are no other treatment options available.

Women with preserved reproductive potential should not use tafluprost if they do not use adequate contraceptives.

Breast-feeding period

It is not known whether tafluprost or its metabolites pass into breast milk. In studies on rats, the penetration of tafluprost into breast milk after topical application was established. Therefore, tafluprost should not be used during breastfeeding.

Fertility

Intravenous use of tafluprost at doses up to 100 mcg / kg / day did not affect mating ability and fertility in female and male rats.

Contraindications

-Hypersensitivity to the Active ingredient tafluprost or to any of the excipients of the drug.

– Age up to 18 years (no data on clinical use).

With caution

Tafluprost should be used with caution in patients with aphakia, pseudophakia with rupture of the posterior lens capsule or with anterior chamber intraocular lenses, as well as in patients with established risk factors for cystoid macular edema or iritis/uveitis.

Tafluprost should be used with caution in patients with aphakia and pigmented or pseudoexfoliative glaucoma.

Tafluprost should be used with caution in patients with neovascular, closed-angle, narrow-angle or congenital glaucoma.

Tafluprost should be used with caution in patients with severe bronchial asthma, in patients with impaired renal/hepatic function.

There is a possibility of hair growth in areas where tafluprost solution is constantly in contact with the skin surface.

Side effects

In clinical trials using tafluprost either as monotherapy or as an adjunct to timolol 0.5%, the most commonly reported treatment-related adverse event was ocular hyperemia. It was observed in approximately 13% of patients participating in clinical trials of tafluprost in Europe and the United States. In most cases, hyperemia was moderate and resulted in discontinuation of treatment in an average of 0.4% of patients.

Adverse events associated with the use of tafuprost are presented below, according to the involvement of organs, organ systems, and frequency of occurrence.

The frequency of adverse reactions is determined as follows: very common (> 1/10), > common (>1/100 and >< 1/10), infrequent(> 1/1000 and >< 1/100), rare (≥ 1/10000 and < 1/1000), very rare (<1/10000), frequency unknown (frequency cannot be determined from available data).

From the nervous system

Often: headache.

On the part of the organ of vision

is Oftenitchy eyes, eye irritation, eye pain, redness of the eye/conjunctiva, eyelash changes (increased length, thickness and number of lashes), dry eyes, change the color of the eyelashes, foreign body sensation in eyes, eyelid erythema, superficial keratitis point (PTK), blurred vision, increased lacrimation, reduced visual acuity, photophobia, and increased pigmentation of the iris.

Infrequently: asthenopia, conjunctival edema, blepharitis, cellular opalescence of anterior chamber moisture, conjunctival follicles, allergic conjunctivitis, inflammatory reaction in anterior chamber moisture, conjunctival pigmentation, eye discomfort, eyelid pigmentation, eyelid edema, eye discharge, atypical sensation in the eye.

Frequency unknown (cannot be estimated from available data): iritis/uveitis, eyelid crease aggravation, retinal macular edema/cystic macular edema.

Very rare cases of calcification in corneal tissue have been reported due to the use of phosphate-containing eye drops in some patients with significant corneal damage.

Respiratory, thoracic and mediastinal

disorders The frequency is unknown: exacerbation of bronchial asthma, shortness of breath.

Skin and subcutaneous tissue disorders

Infrequently: hypertrichosis of the eyelids.

Interaction

Due to the low concentration of tafluprost in the blood plasma after instillation of the drug, no cross-interactions with other drugs are expected.

Studies on the specific interactions of tafluprost with other drugs have not been conducted.

When tafluprost was co-administered with timolol in clinical studies, there were no signs of interaction.

How to take, course of use and dosage

Doses

The recommended dose is one drop of Taflopress Rompharm into the conjunctival sac of the affected eye once a day, in the evening. The dose should be instilled strictly once a day, since more frequent use may reduce the effect of lowering IOP.

Method of application

To prevent possible contamination of the solution, patients should not allow the tip of the bottle to touch the eyelids, the skin around the eyes or any other surfaces.

To reduce the risk of darkening the skin of the eyelids, patients should remove excess solution from the skin. As with other eye drops, short-term nasolacrimal occlusion or gentle closing of the eyelids after instillation of the drug is recommended. This may reduce the systemic absorption of the drug.

When using several ophthalmic medications, the intervals between their use should be at least 5 minutes.

Special patient groups

Elderly patients

No dose adjustment is required in elderly patients.

Children

The safety and efficacy of tafluprost in children under 18 years of age have not been established.

Impaired renal/hepatic function

There are no data on the use of tafluprost in patients with renal/hepatic insufficiency. In this regard, caution should be exercised when using the drug in these groups of patients.

Overdose

After instillation of the drug in the eye, overdose is unlikely. In case of overdose, treatment should be symptomatic.

Description

Colorless, transparent solution.

Special instructions

Before starting treatment, patients should be informed about the possibility of eyelash growth, darkening of the eyelid skin and increased pigmentation of the iris. Some of these changes may be permanent and may lead to differences between the eyes if the drug is only instilled in one eye.

Changes in the pigmentation of the iris occur slowly and may remain unnoticeable for several months. The change in eye color is mainly observed in patients with mixed-colored irises, for example, if the eyes are brown-blue, gray-brown, yellow-brown or green-brown. Treating only one eye can lead to persistent heterochromia.

There is no experience of using tafluprost in neovascular, closed-angle, narrow-angle or congenital glaucoma.

There is limited experience with tafluprost in patients with aphakia and pigmented or pseudoexfoliative glaucoma.

Tafluprost should be used with caution in patients with aphakia, pseudophakia with rupture of the posterior lens capsule or with anterior chamber intraocular lenses, as well as in patients with established risk factors for cystoid macular edema or iritis/uveitis.

There is no experience of using tafluprost in patients with severe bronchial asthma and in patients with impaired renal/hepatic function, so the drug should be used with caution in these patients.

There is a possibility of hair growth in areas where tafluprost solution is constantly in contact with the skin surface.

Influence on the ability to drive vehicles and mechanisms

Tafluprost does not affect the ability to drive vehicles and mechanisms. As with the use of any other ophthalmic agents, short-term blurred vision may occur after instillation of the drug, so it is necessary to refrain from driving vehicles and performing activities that require increased concentration of attention and speed of psychomotor reactions until vision is restored.

Form of production

Eye drops 0.015 mg / ml.

2.5 ml of the drug is placed in a polymer bottle with a capacity of 5 ml with a dropper plug, closed with a polymer lid with a safety ring. One bottle together with the instructions for use is placed in a cardboard box.

Storage conditions

At a temperature of 2-8 °C, in the original packaging.

After opening the bottle, store at a temperature not exceeding 25 °C.

Keep out of the reach of children!

Shelf

life is 3 years. After the first opening of the bottle – 4 weeks. Do not use after the expiration date!

Active ingredient

Tafluprost

Conditions of release from pharmacies

By prescription

Dosage form

eye drops