Тафлотан®

General characteristics. Structure:

Active ingredient: 15 mkg of a tafluprost.

Excipients: глицерол - 22.5 mg, hydrophosphate sodium a dihydrate - 2 mg, dinatrium эдетат - 0.5 mg, polysorbate of 80 - 0.75 mg, Acidum hydrochloricum and/or sodium hydroxide (for correction pH), water for and - to 1 ml.

Pharmacological properties:

Pharmacodynamics. Protivoglaukomny drug, the fluorinated F2α prostaglandin analog. Action mechanism. Acid of a tafluprost, being its biologically active metabolite, has high activity and selectivity concerning a FP prostanoid receptor of the person. Affinity of acid of a tafluprost to a FP receptor is 12 times higher, than affinity of a latanoprost. Pharmakodinamichesky researches on monkeys showed what тафлупрост reduces the intraocular pressure (VGD), strengthening uveoskleralny outflow of watery moisture.

Pharmakodinamichesky effect. Experiments on monkeys with the normal and raised VGD showed what тафлупрост is effective medicine for decrease in VGD. In a research on studying VGD-ponizhayushchego of effect of metabolites of a tafluprost, it was revealed that only acid of a tafluprost considerably reduces VGD.

Researches on the rabbits treated within 4 weeks with ophthalmologic solution of a tafluprost of 0.0015% of 1 times/days showed that the blood stream in an optic disk considerably (for 15%) amplified in comparison with initial level, at measurement for the 14 and 28 day with use laser a speckle-flougrafii.

Clinical effect. Decrease in VGD begins within 2-4 hours after the first installation of drug, and the maximum effect is reached approximately in 12 h. Duration of effect remains, at least, during 24 h. The leading researches on use of the tafluprost containing preservative a benzalkoniya chloride showed that тафлупрост it is effective as monotherapy, and also has the additive effect at its use as additional therapy to Timololum. In a 6-month research it is shown essential VGD-ponizhayushchy effect of a tafluprost in various temporary points during the day: from 6 to 8 mm of mercury., in comparison with latanoprosty, the reducing VGD on 7-9 mm of mercury. In other 6-month clinical trial тафлупрост lowered VGD by 5-7 mm of mercury., and Timololum on 4-6 mm of mercury. VGD-ponizhayushchy the effect of a tafluprost remained as well at increase in duration of these researches up to 12 months. In the 6 weeks research VGD-ponizhayushchy the effect of a tafluprost was compared to effect of its indifferent filler at use in total with Timololum. In comparison with initial indicators (measurement was taken after 4 week courses of treatment with Timololum) additional VGD-ponizhayushchy the effect made 5-6 mm of mercury. in Timololum-tafluprost to group and 3-4 mm of mercury. - in group Timololum - an indifferent filler.

In a small cross research, with the 4 weeks period of treatment, it was shown similar VGD-ponizhayushchy effect of dosage forms with preservative and without preservative - more than 5 mm of mercury.

Besides, in a 3-month research in the USA when comparing, structure of a tafluprost without preservative with Timololum, also without preservative, it was established that тафлупрост VGD lowered by 6.2-7.4 mm hg in different temporary points whereas values for Timololum varied between 5.3 and 7.5 mm hg.

Pharmacokinetics. Absorption. After instillation of eye drops тафлупрост 0.0015% in a tube dropper, without preservative, 1 times/days on 1 drop in both eyes within 8 days, concentration of a tafluprost in plasma were low and had a similar profile for the 1 and 8 day. Cmax in plasma was reached in 10 min. after instillation, and decreased to level, lower, than the lower limit of detection (10 pg/ml) less than for 1 h after administration of drug. The average sizes Cmax (26.2 and 26.6 pg/ml) and AUC0 last (394.3 and 431.9 пг/мин/мл) were almost identical for the 1 and 8 day that demonstrates that already within the first week of treatment, stable concentration of drug was reached. Between dosage forms with preservative and without preservative no statistically significant distinctions in system bioavailability were revealed.

In a research on rabbits, absorption of a tafluprost in watery moisture, after single instillation of ophthalmologic solution of a tafluprost of 0.0015% with preservative and without preservative, was comparable.

Distribution. Linkng of acid of a tafluprost with a seralbumin of the person of in vitro makes 99% at concentration of acid of a tafluprost of 500 ng/ml.

In a research on monkeys, specific distribution marked by the radioactivity of a tafluprost in an iris, a ciliary body or in an eye choroid, including a retinal pigmental epithelium was not noted that testifies to low affinity of drug to a melaninovy pigment.

The Autoradiografichesky research on rats, showed that the highest concentration of radioactivity was observed in a cornea, and then in centuries, a sclera and an iris of the eye. Systemically radioactivity extended to the lacrimal device, the sky, a gullet, a GIT, kidneys, a liver, bilious and a bladder.

Metabolism. The main way of metabolism of a tafluprost in a human body, the tested hydrolysis of in vitro with education pharmacological an active metabolite, acid of a tafluprost which then is metabolized by means of a glyukuronization or beta oxidation with formation pharmacological of inactive 1,2 diholes and 1,2,3,4 tetraholes of acids of a tafluprost which can be exposed to a glyukuronization or a hydroxylation. The fermental system of P450 cytochrome does not participate in metabolism of acid of a tafluprost. In the research conducted on fabrics of a cornea of a rabbit with the refined enzymes it was revealed that the main esterase of the acid of a tafluprost which is responsible for radio hydrolysis is the karboksilesteraza. Butyrylcholinesterase, but not acetylcholinesterase, can also promote hydrolysis.

Removal. In a research on rats, after single instillation of a 3H-tafluprost (0.005% of ophthalmologic solution, 5 мкл / an eye) in both eyes within 21 days, about 87% of the general radioactive dose were revealed in excrement. With urine about 27-38% of the general dose, with a stake - about 44-58% were removed.

Indications to use:

For decrease in the increased intraocular pressure at patients with an open angle glaucoma and an oftalmogipertenziya as monotherapy at patients:

— to which the eye drops which are not containing preservative are shown;

— with insufficient reaction to drugs of the first line of therapy;

— not transferring drugs of the first line or having contraindications to these drugs.

As additional therapy to beta adrenoblockers.

Тафлупрост it is intended for patients 18 years are more senior.

Route of administration and doses:

The recommended dose - 1 drop of eye drops of Taflotan® in a conjunctival sac of the affected eye (eyes) of 1 times/days, in the evening.

Drug in the specified dose it is necessary to dig in strictly 1 times/days since more frequent use can reduce effect of decrease in VGD.

Only for single use. One tube dropper is enough contents for an instillation in both eyes. The remained drug has to be thrown out immediately after use.

Dose adjustment is not required from patients of advanced age.

Safety and efficiency of a tafluprost at children and teenagers aged up to 18 years is not established, data on use are not available.

Efficiency and safety of a tafluprost at patients with disturbances of functions of a liver and/or kidneys are not studied therefore in need of use of drug for this category of patients care is required.

Route of administration. To reduce risk of darkening of skin a century, patients should delete excess of solution from skin.

As well as at use of other eye drops lacrimonasal occlusion - soft closing after drug instillation is recommended a century. It can reduce system absorption of the medicines administered through eyes.

At use of several ophthalmologic drugs of local action, intervals between their use have to make not less than 5 min.

Features of use:

Use at pregnancy and feeding by a breast. Data on use of a tafluprost for pregnant women are not enough. Тафлупрост can make an adverse pharmacological effect on the course of pregnancy and/or on the child's fruit/newborn. In this regard Taflotan® should not be applied at pregnancy, except for cases, when there is no other options of treatment.

Women of childbearing age should not appoint Taflotan® if they do not apply adequate contraceptives.

It is unknown whether are allocated тафлупрост or its metabolites with breast milk at the person. Тафлотан® it is not necessary to apply during breastfeeding.

In pilot studies on animals toxic impact of a tafluprost on reproductive system is shown. In a research on rats it was established what after topical administration тафлупрост is allocated with breast milk. Fertility of female and men's individuals of rats, ability to pairing and birth rate remained invariable at introduction of a tafluprost to 100 mkg/kg/days in / century.

Prior to treatment of patients it is necessary to warn about a possibility of overgrowth of eyelashes, darkenings of skin a century and strengthenings of pigmentation of an iris of the eye of an eye. Some of the specified changes can be permanent, and it can result in distinctions in outward of eyes if only one eye was exposed to treatment.

Change of pigmentation of an iris of the eye happens slowly, and within several months can remain imperceptible. Discoloration of eyes is observed preferential at patients with irises of the eye of the mixed flowers, for example, if eyes brown-blue, gray-brown, yellowy-brown or green-brown. Treatment only of one eye can lead to a resistant heterochromia.

There is no experience of use of a tafluprost in cases of neovascular, closed-angle, narrow or inborn angle glaucoma. There is only a limited experience of treatment tafluprosty patients with an aphakia, pigmental or pseudo-exfoliative glaucoma.

It is recommended to be careful at treatment tafluprosty patients with an aphakia, the artifakiya damaged by the back capsule of a crystalline lens or implantation of a crystalline lens in an anterior chamber of an eye and also patients with the established risk factors of development of kistoidny macular hypostasis or an iritis/uveitis.

There is no experience of use of drug for patients with heavy asthma. In this regard patients of this group should be treated with care.

Influence on ability to driving of motor transport and to control of mechanisms

Тафлупрост does not exert impact on ability to control of vehicles and work with mechanisms. As well as at use of any other ophthalmologic means, after installation of drug there can be short-term misting of sight. In this case the patient has to wait so far sight completely will be recovered and only after that to drive the car or to work with the mechanical equipment.

Side effects:

In clinical trials over 1400 patients were treated tafluprosty with preservative - either as monotherapy, or as additional drug to treatment by Timololum of 0.5%. The hyperemia of eyes was the most often revealed side effect connected with treatment. It was noted approximately at 13% of the patients who were taking part in clinical trials of a tafluprost in Europe and the USA. In most cases the hyperemia was moderate and led to the treatment termination on average at 0.4% of patients. In a 3-month research III of a phase, in the USA when comparing structure of a tafluprost of 0.0015% without preservative, with Timololum, also without preservative, the hyperemia of eyes was noted at 4.1% (13/320) patients receiving тафлупрост.

The following side effects connected with treatment were registered during clinical trials of a tafluprost in Europe and the USA after their maximum expansion up to 24 months.

From an organ of sight: often (from> 1/100 to <1/10) - an itch of eyes, irritation of eyes, eye pain, a hyperemia of conjunctivas/a eyes, changes of eyelashes (increase in length, thickness and number of eyelashes), a syndrome of a dry eye, feeling of a foreign body in eyes, discoloration of eyelashes, an erythema a century, a superficial dot keratitis, photophobia, the raised slezootdeleniye, sight misting, decrease in visual acuity, and the increased pigmentation of an iris of the eye; infrequently (from> 1/1000 to <1/100) - pigmentation a century, the century, an asthenopia, a chemosis, emergence separated from eyes, a blepharitis, an inflammation of an anterior chamber, a sensation of discomfort in eyes, a crape of an anterior chamber of an eye, pigmentation of a conjunctiva, conjunctival follicles, allergic conjunctivitis and atypical feeling in an eye swelled.

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

From skin and hypodermic fabrics: infrequently (from> 1/1000 to <1/100) - a hypertrichosis a century.

Interaction with other medicines:

No cross interaction with other drugs at treatment of people as concentration of a tafluprost in a system blood-groove, after instillation of drug in eyes, extremely low therefore special researches on studying of specific interaction of a tafluprost with other medicines were not conducted is expected.

In clinical trials тафлупрост it was applied along with Timololum, at the same time no symptoms of cross interaction were noted.

Contraindications:

— hypersensitivity to drug components.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature from 2 °C to 8 °C. A period of validity - 3 years. After opening of a package about a tube droppers to store at a temperature not above 25 °C. To store a tube dropper in a package. A period of validity - 4 weeks. After a tube dropper disposable it is necessary to throw out together with the available rest.

Issue conditions:

According to the recipe

Packaging:

0.3 ml - a tube dropper (10), soldered in the form of a plastic tape - packages from the laminated aluminum foil (3) - packs cardboard.