Taflotan drops 0.0015%, 0.3ml No. 30

To reduce increased intraocular pressure in patients with open-angle glaucoma and ophthalmic hypertension as monotherapy in patients:

• which are indicated for eye drops that do not contain a preservative;

• with insufficient response to first-line drugs;

• intolerant of first-line drugs or having contraindications to these drugs.

As an adjunct therapy to beta-blockers.

Tafluprost is intended for patients over 18 years of age.

The recommended dose is 1 drop of TaflotanЃ into the conjunctival sac of the affected eye (s) 1 time / day, in the evening.

The drug in the indicated dose should be instilled strictly 1 time / day, because more frequent use can reduce the effect of lowering IOP.

For single use only. The contents of one dropper tube are sufficient for instillation in both eyes. The remaining drug should be disposed of immediately after use.

No dose adjustment is required in elderly patients.

The safety and efficacy of tafluprost in children and adolescents under the age of 18 has not been established, data on its use are not available.

The efficacy and safety of tafluprost in patients with impaired liver and / or kidney function have not been studied, therefore, if it is necessary to use the drug in this category of patients, caution is required.

Mode of application

To reduce the risk of darkening of the eyelid skin, patients should remove excess solution from the skin.

As with other eye drops, nasolacrimal occlusion is recommended - gentle closure of the eyelids after instillation of the drug. This can reduce the systemic absorption of drugs administered by instillation into the conjunctival sac.

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

Eye drops in the form of a clear, colorless solution.

1 ml

tafluprost 15 mcg

Excipients: glycerol - 22.5 mg, sodium hydrogen phosphate dihydrate - 2 mg, disodium edetate - 0.5 mg, polysorbate 80 - 0.75 mg, hydrochloric acid and / or sodium hydroxide (for pH correction), water d / i - up to 1 ml.

hypersensitivity to the components of the drug.

pharmachologic effect

An antiglaucoma drug, a fluorinated analogue of prostaglandin F2 ?.

Mechanism of action

The acid of tafluprost, being its biologically active metabolite, has high activity and selectivity for the human FP-prostanoid 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), increasing the uveoscleral outflow of aqueous humor.

Pharmacodynamic effect

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

Studies on rabbits treated for 4 weeks with an ophthalmic solution of tafluprost 0.0015% 1 time / day showed that the blood flow in the optic nerve head increased significantly (by 15%) compared to the initial level, when measured on days 14 and 28 using a laser speckle flowgraphs.

Clinical effect

The decrease in IOP begins within 2-4 hours after the first instillation of the drug, the maximum effect is achieved after about 12 hours.The duration of the effect lasts for at least 24 hours. effective as a monotherapy, and also has an additive effect when used as an adjunct therapy to timolol. A 6-month study showed a significant IOP-lowering effect of tafluprost at various time points throughout the day: from 6 to 8 mm Hg. Art., compared with latanoprost, which reduces IOP by 7-9 mm Hg. Art.

In another 6-month clinical study, tafluprost reduced IOP by 5-7 mm Hg. Art., and timolol by 4-6 mm Hg. Art. The IOP-lowering effect of tafluprost also persisted with an increase in the duration of these studies to 12 months. In a 6-week study, the IOP-lowering effect of tafluprost was compared to that of an indifferent filler when used in conjunction with timolol. Compared to the baseline (measured after a 4-week course of treatment with timolol), the additional IOP-lowering effect was 5-6 mm Hg. Art. in the timolol-tafluprost group and 3-4 mm Hg. Art. - in the group timolol-indifferent filler.

In a small crossover study with a 4-week treatment period, a similar IOP-lowering effect of preservative and non-preservative dosage forms was demonstrated - more than 5 mm Hg. Art.

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

Pharmacokinetics

Suction

After instillation of eye drops tafluprost 0.0015% in a dropper tube, without preservative, 1 time / day, 1 drop in both eyes for 8 days, plasma concentrations of tafluprost were low and had a similar profile on days 1 and 8. Cmax in plasma was reached 10 minutes after instillation and decreased to a level lower than the lower detection limit (10 pg / ml) in less than 1 hour after drug administration. The average values ??of Cmax (26.2 and 26.6 pg / ml) and AUC0-last (394.3 and 431.9 pg / min / ml) were almost the same on days 1 and 8, which indicates that a stable concentration was achieved already during the first week of treatment. drug. There were no statistically significant differences in systemic bioavailability between preservative and non-preservative dosage forms.

In a study on rabbits, the absorption of tafluprost into aqueous humor after a single instillation of an ophthalmic solution of tafluprost 0.0015% with a preservative and without a preservative was comparable.

Distribution

The in vitro binding of tafluprost acid to human serum albumin is 99% at a tafluprost acid concentration of 500 ng / ml.

In a study in monkeys, there was no specific distribution of radioactively labeled tafluprost in the iris, ciliary body or in the choroid of the eye, including the retinal pigment epithelium, which indicates a low affinity of the drug for the melanin pigment.

An autoradiographic study in rats showed that the highest concentration of radioactivity was observed in the cornea, and then in the eyelids, sclera and iris. Systemically, radioactivity spread to the lacrimal apparatus, palate, esophagus, gastrointestinal tract, kidneys, liver, gallbladder and bladder.

Metabolism

The main metabolic pathway of tafluprost in the human body, tested in vitro, is hydrolysis with the formation of a pharmacologically active metabolite, tafluprost acid, which is then metabolized by glucuronization or beta-oxidation to form pharmacologically inactive 1,2-dinor and 1,2,3,4- tetranor acids of tafluprost, which can undergo glucuronidation or hydroxylation. The enzyme system of cytochrome P450 is not involved in the metabolism of tafluprost acid. In a study carried out on the tissues of the cornea of ??a rabbit with refined enzymes, it was found that the main esterase responsible for the ester hydrolysis of tafluprost acid is carboxylesterase. Butyrylcholinesterase, but not acetylcholinesterase, can also promote hydrolysis.

Withdrawal

In a study on rats, after a single instillation of 3H-tafluprost (0.005% ophthalmic solution, 5 ?l / eye) in both eyes for 21 days, about 87% of the total radioactive dose was found in excrement. About 27-38% of the total dose was excreted with urine, with feces - about 44-58%.

Side effect

In clinical trials, over 1400 patients were treated with tafluprost with a preservative, either as monotherapy or as an adjunct to timolol 0.5%. The most commonly reported treatment-related side effect was conjunctival injection. It was observed in about 13% of patients who took part in clinical trials of tafluprost in Europe and the United States. In most cases, hyperemia was moderate and led to discontinuation of treatment in an average of 0.4% of patients. In a 3-month phase III study in the United States, comparing the composition of tafluprost 0.0015% without preservative with timolol, also without preservative, conjunctival injection was observed in 4.1% (13/320) of patients receiving tafluprost.

The following treatment-related side effects have been reported in clinical trials of tafluprost in Europe and the United States after their maximum extension to 24 months.

Within each group of effects, combined by frequency of occurrence, side effects are presented according to their severity in descending order.

From the nervous system: often (from? 1/100 to <1/10) - headache.

From the side of the organ of vision: often (from? 1/100 to <1/10) - itchy eyes, eye irritation, eye pain, conjunctival injection, changes in eyelashes (increase in the length, thickness and number of eyelashes), dry eye syndrome, foreign sensation body in the eyes, discoloration of eyelashes, erythema of the eyelids, superficial punctate keratitis, photophobia, increased lacrimation, blurred vision, decreased visual acuity, increased pigmentation of the iris; infrequently (from? 1/1000 to <1/100) - eyelid pigmentation, eyelid edema, asthenopia, conjunctival edema, the appearance of discharge from the eyes, blepharitis, an inflammatory reaction in the moisture of the anterior chamber, a feeling of discomfort in the eyes, conjunctival pigmentation, conjunctival follicles, allergic conjunctivitis and atypical sensation in the eye; frequency unknown (cannot be determined from the available data) - iritis / uveitis,deepening of the crease of the eyelid.

Very rare cases of corneal calcifications have been reported in association with the use of phosphate-containing eye drops in some patients with significant corneal involvement.

From the respiratory system: the frequency is unknown (cannot be determined on the basis of available data) - exacerbation of bronchial asthma, shortness of breath.

Skin and subcutaneous tissue disorders: infrequently (from? 1/1000 to <1/100) - eyelid hypertrichosis.

Application during pregnancy and lactation

There is insufficient data on the use of tafluprost in pregnant women. Tafluprost may have adverse pharmacological effects on pregnancy and / or on the fetus / newborn baby. In this regard, TaflotanЃ should not be used during pregnancy, unless there are no other treatment options.

Women of childbearing age should not be prescribed TaflotanЃ if they are not using adequate contraception.

It is not known whether tafluprost or its metabolites are excreted in human breast milk. TaflotanЃ should not be used during breastfeeding.

In a study on rats, it was found that after topical application, tafluprost is excreted in breast milk.

The fertility of female and male rats, the ability to mate and fertility remained unchanged with the introduction of tafluprost up to 100 ?g / kg / day IV.

Application for violations of liver function

The efficacy and safety of tafluprost in patients with impaired liver function have not been studied, therefore, if it is necessary to use the drug in this category of patients, caution is required.

Application for impaired renal function

The efficacy and safety of tafluprost in patients with impaired renal function have not been studied, therefore, if it is necessary to use the drug in this category of patients, caution is required.

Application in children

Tafluprost is intended for patients over 18 years of age.

Use in elderly patients

No dose adjustment is required in elderly patients.

special instructions

Before starting treatment, patients should be warned about the possibility of excessive eyelash growth, darkening of the eyelid skin and increased pigmentation of the iris. Some of these changes can be permanent, which can lead to differences in the appearance of the eyes if only one eye has been treated.

The change in the pigmentation of the iris is slow and may not be noticeable for several months. Eye discoloration occurs predominantly in patients with mixed-colored irises, for example, if the eyes are brownish blue, taupe, tan, or greenish brown. Treatment of only one eye can lead to persistent heterochromia.

There is no experience of using tafluprost in cases of neovascular, closed-angle, narrow-angle or congenital glaucoma. There is only limited experience in the treatment of patients with aphakia, pigmentary or pseudoexfoliative glaucoma with tafluprost.

Caution is advised when treating tafluprost in patients with aphakia, pseudophakia, damaged posterior lens capsule or lens implantation into the anterior chamber of the eye, as well as in patients with established risk factors for developing cystic macular edema or iritis / uveitis.

There is no experience of using the drug in patients with severe asthma. In this regard, patients in this group should be treated with caution.

Influence on the ability to drive vehicles and use mechanisms

Tafluprost does not affect the ability to drive vehicles and work with mechanisms. As with the use of any other ophthalmic agents, short-term blurred vision may occur after instillation of the drug. In this case, the patient must wait until vision is fully restored and only then drive a car or work with mechanical equipment.

Overdose

Overdose cases were not reported. After instillation of the drug into the eye, overdose is unlikely.

Treatment: in case of an overdose, symptomatic therapy is performed.

Drug interactions

No cross-interaction with other drugs is expected, since the concentration of tafluprost in the systemic circulation after instillation of the drug in the eye is extremely low, therefore, special studies to study the specific interaction of tafluprost with other drugs have not been conducted.

In clinical trials, tafluprost was used concomitantly with timolol, and no symptoms of cross-talk were observed.