Taflotan, eye drops 0.0015% 0.3 ml 30 pcs

Tafluprost is a fluorinated analogue of prostaglandin F2α. As its biologically active metabolite, tafluprost acid is highly active and selective for the human FP-prostanoid receptor. The affinity of tafluprost acid to the FP-receptor is 12 times higher than the affinity of latanoprost. Pharmacodynamic studies in monkeys have shown that tafluprost reduces intraocular pressure by increasing uveoscleral outflow of aqueous humor.

Pharmacodynamic Effect

The experiments in monkeys with normal and elevated intraocular pressure (IOP) have demonstrated that tafluprost is an effective drug for reducing IOP. In a study examining the IOP-lowering effects of tafluprost metabolites, tafluprost acid alone was found to significantly lower IOP.

The study, on rabbits treated for 4 weeks with tafluprost ophthalmic solution, 0.0015%, once daily, showed that blood flow in the optic disc was significantly (15%) increased compared to baseline, when measured at day 14 and 28 using laser speckle flowography.

The clinical effect

The decrease in intraocular pressure begins within 2-4 hours after the first instillation of the drug, and the maximum effect is achieved after about 12 hours. The duration of the effect lasts for at least 24 hours. Leading studies on the use of tafluprost containing the preservative benzalkonium chloride have shown that tafluprost is effective as monotherapy and also has an additive effect when used as an additional therapy to timolol. In a 6-month study, tafluprost, at various time points during the day, demonstrated a significant, IOP-lowering effect: 6 to 8 mmHg, compared with latanoprost, which reduced IOP by 7 to 9 mmHg.

In another 6-month clinical trial, tafluprost reduced IOP by 5 to 7 mmHg and timolol by 4 to 6 mmHg. The IOP-lowering effect of tafluprost also persisted when the duration of these studies was increased to 12 months. In a 6-week study, the IOP-lowering effect of tafluprost was compared with that of its indifferent filler when used in combination with timolol. Compared with baseline values (measured after 4 weeks of treatment with timolol), the additional IOP-lowering effect was 5-6 mm Hg in the timolol-tafluprost group and 3-4 mm Hg in the timolol-idifferent filler group. In a small cross-sectional study, with a 4-week treatment period, the drug forms with and without the preservative showed a similar IOP-lowering effect of more than 5 mm Hg.

In addition, in a 3-month study in the United States, when comparing, the formulation of tafluprost without preservative with timolol. also without preservative, tafluprost was found to reduce IOP by 6.2-7.4 mmHg at different time points, whereas values for timolol varied between 5.3 and 7.5 mmHg.

Pharmacokinetics

Absorption

. After instillation of tafluprost eye drops, 0.0015% in a tube dropper, without preservative, once daily, one drop in both eyes for 8 days, its plasma concentrations were low and had a similar profile on days 1 and 8. Plasma concentrations peaked 10 minutes after instillation and declined to a level lower than the lower limit of detection (10 pg/ml) in less than an hour after administration. The mean Cmax (26.2 and 26.6 pg/ml) and AUCo-last (394.3 and 431.9 pg/ml) values were almost identical on days 1 and 8, indicating that within the first week of treatment, a stable drug concentration was already achieved. No statistically significant differences in systemic bioavailability were observed between dosage forms with and without a preservative.
In a study on rabbits, the absorption of tafluprost into aqueous humor, after a single instillation of tafluprost ophthalmic solution, 0.0015% with and without a preservative, was comparable.

Distribution

In a study on monkeys, there was no specific distribution of radioactively labeled tafluprost in the iris, ciliary body, or ocular vasculature, including the retinal pigment epithelium, indicating a low affinity of the drug for melanin pigment.

Autoradiographic study in rats showed that the highest concentration of radioactivity was observed in the cornea, followed by the eyelids, sclera and iris. Systemically, radioactivity spread to the lacrimal system, palate, esophagus, gastrointestinal tract, kidneys, liver, gallbladder, and bladder. The in vitro binding of tafluprost acid to human serum albumin is 99% for 500 ng/mL of tafluprost acid.

Biotransformation

. The major pathway of metabolism of tafluprost in humans tested in vitro is hydrolysis to form the pharmacologically active metabolite, tafluprost acid, which is then mstabolized by glucuronidation or beta-oxidation to form pharmacologically inactive 1,2-dinor and 1,2,3,4-tetranor tafluprost acids, which can be glucuronidated or hydroxylated. The cytochrome P450 enzyme system (CYP) is not involved in metabolism of tafluprost acid. In a study performed on rabbit corneal tissue with refined enzymes, carboxylesterase was found to be the major esterase responsible for ester hydrolysis of tafluprost acid. Butyrylcholinesterase, but not acetylcholinesterase, can also contribute to hydrolysis.

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

Indications

Active ingredient

Composition

1 ml of eye drops contains:

the active ingredients:

tafluprost 15 mcg;

excipients:

glycerol – 22.5 mg,

sodium hydrophosphate dihydrate – 2 mg,

dinatrate edetate – 0.5 mg,

polysorbate 80 – 0.75 mg,

Hydrochloric acid and/or sodium hydroxide (for pH correction),

d/i water – up to 1 ml.

How to take, the dosage

The recommended dose is one drop of Taflotan eye drops into the conjunctival sac of the affected eye (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 reducing intraocular pressure.

Daily use only. The contents of one tube of dropper are sufficient to be injected into both eyes. The remaining product must be discarded immediately after use.

Application in elderly patients

There is no need to change the dose when treating elderly patients.

Application in children and adolescents

The safety and effectiveness of Tafluprost in children and adolescents under 18 years of age has not been established. No data are available.

Use in renal/liver disorders

There have been no studies on the effects of tafluprost on patients with renal/liver disorders, so caution should be exercised when treating this patient population.

Method of Administration

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 – gently closing the eyelids after instillation of the medication – is recommended. This may reduce the systemic absorption of medications administered through the eye.

If multiple topical ophthalmic medications are used, there should be at least 5-minute intervals between applications.

Interaction

No cross interactions with other drugs are to be expected because systemic concentrations of tafluprost are extremely low after eye injection. There have been no specific studies of specific cross-interactions of tafluprost with other medical products.

Tafluprost has been used concomitantly with timolol in clinical studies with no evidence of cross-interactions.

Special Instructions

Patients should be warned of the possibility of excessive eyelash growth, darkening of the eyelid skin, and increased pigmentation of the irises before treatment begins. Some of these changes may be permanent, and this can lead to differences in the appearance of the eyes if only one eye is treated.

Irispigmentation changes are slow and may not be noticed for several months. Color changes of the eyes occur mostly in patients with irises of mixed colors, for example, if the eyes are brownish-blue, grayish-brown, yellow-brown, or green-brown. There may be a risk of lifelong heterochromia if only one eye is treated.
There is no experience with tafluprost in cases of neovascular, closed angle, narrow angle or congenital glaucoma.There is only limited experience with tafluprost in patients with aphakia, pigmentary or pseudoexfoliative glaucoma.
Caution is advised when treating with tafluprost in patients with aphakia, artifactia, damaged posterior lens capsule or anterior chamber lens or in patients with established risk factors for cystoid macular edema or iritis/veitis.

There is no experience with the drug in patients with severe asthma. Therefore, patients in this group should be treated with caution.
Benzalkonium chloride, which is commonly used as a preservative in ophthalmic preparations, has been reported to cause pitting keratopathy and/or toxic ulcerative keratopathy. Because Taflotan contains benzalkonium chloride in vials, close monitoring is necessary in cases of frequent or prolonged use in patients with dry eyes and in cases where the cornea is at risk.
Benzalkonium chloride can also cause eye irritation and discoloration of soft contact lenses. Contact with soft contact lenses should be avoided. Remove contact lenses before applying the product and insert them again at least 15 minutes after instillation.

Impact on driving and operating machinery

Tafluprost has no effect on the ability to drive and operate machinery. As with any other ophthalmologic agent, brief blurring of vision may occur after installation of the drug. In this case the patient should wait until the vision is restored, and only then drive a car or operate mechanical equipment.

Contraindications

Hypersensitivity to Thafluprost or any of the inert fillers of Thaflothane.

Side effects

In clinical trials, more than 1,400 patients were treated with tafluprost with preservative – either as monotherapy or as an adjunct to treatment with timolol, 0.5%. The most frequently identified treatment-related side effect was ocular hyperemia. It was reported in approximately 13% of patients participating in clinical trials of tafluprost in Europe and the United States. In most cases, the hyperemia was moderate and led to treatment discontinuation in an average of 0.4% of patients. In a 3-month phase III study in the United States comparing, tafluprost formulation 0.0015% without preservative, with timolol, also without preservative, eye hyperemia was noted 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:

Ophthalmic

Frequent (> 1/100 to < 1/10): Itchy eyes, eye irritation, eye pain, conjunctival/eye hyperemia, eyelash changes (increased length, thickness, and number of lashes), dry eye syndrome, foreign body sensation in eyes, color changes in eyelashes, eyelid erythema, superficial pitting keratitis, photophobia, increased tear production, blurred vision, reduced visual acuity, and increased iris pigmentation.

Infrequent (> 1/1000 to < 1/100): eyelid pigmentation, eyelid edema, asthenopia, conjunctival edema, ocular discharge, blepharitis, anterior chamber inflammation, eye discomfort sensation, anterior chamber flare, conjunctival pigmentation, conjunctival follicles, allergic conjunctivitis, and atypical feeling in the eye.

Nervous system disorders

Frequent (> 1/100 to < 1/10): Headache

Skin and subcutaneous tissue disorders

Infrequent (> 1/1000 to < 1/100): hypertrichosis of the eyelids

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Overdose

Symptoms: There have been no reports of overdose.

After injection of the drug into the eye an overdose is unlikely.

In case of overdose, treatment should be symptomatic.

Pregnancy use

Women of childbearing potential/ contraception
Women of childbearing potential should not use tafloprost unless they are using adequate contraception.

Pregnancy
There are insufficient 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/infant. Animal studies have demonstrated toxic effects on the reproductive system. Therefore, Taflotan should not be used during pregnancy unless there are no other treatment options.

Breastfeeding
It is not known whether tafluprost or its metabolites penetrate human breast milk. In a study in rats, excretion of tafluprost into breast milk after topical administration was determined. Therefore, taflutane should not be used during breastfeeding.

Fertility
In female and male rats, mating ability and fertility remained unchanged when tafluprost was administered up to 100 µg/kg/day intravenously.