Taflotan - instructions for use, dose, side effects, contraindications

Active substanceTafluprostTafluprost

Similar drugsTo uncover

Taflotan®

drops d / eye

Santen, AO Finland

Dosage form: & nbspeye drops

Composition:

1 ml of eye drops contains:

Active substance:

Tafluprost 15 μg Excipients:

Glycerol 22.5 mg sodium phosphate dihydrate 2 mg Disodium edetate 0.5 mg Polysorbate 80 0.75 mg, sodium hydroxide and / or hydrochloric acid to correct pH, water for injections to 1 mL.

Description:A clear, colorless solution.

Pharmacotherapeutic group:Antiglaucoma drugs and myotics, prostaglandin analogues.

ATX: & nbsp

Tafluprost

Pharmacodynamics:

Mechanism of action

Tafluprost is a fluorinated analogue of prostaglandin F2_a. Tafluprost acid, being a biologically active metabolite has high activity and selectivity for FPhuman prostanoid receptor. The affinity of tafluprost acid for FP-receptor is 12 times higher than the affinity of latanoprost. Pharmacodynamic studies on monkeys have shown that tafluprost reduces intraocular pressure, enhancing the outgrowth outflow of watery moisture.

Pharmacodynamic effect

Experiments on monkeys with normal and elevated intraocular pressure (IOP) demonstrated that Tafluprost is an effective drug for reducing IOP. In a study on the IHD-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 tufluprost solution, 0.0015%, once a day, showed that blood flow in the optic nerve disk significantly (by 15%) increased in comparison with baseline, when measured at 14 and 28 day using laser speckle of flowery.

Clinical effect

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 is maintained for at least 24 hours. Leading research on the use of preservative-containing tafluprost benzalkonium chloride, showed that tafluprost is effective as a monotherapy, and also has an additive effect when applied as an adjunct 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 mm Hg. in comparison with latanoprost, which reduces IOP by 7-9 mm Hg. ..

In another 6-month clinical trial tafluprost decreased IOP by 5-7 mm Hg. art., and timolol for 4-6 mm Hg. The IOP-lowering effect of tafluprost was also maintained 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 the effect of its indifferent excipient when used in conjunction with timolol. Compared with baseline (measurement was performed after a 4-week course of treatment with timolol), the additional IOP-lowering effect was 5-6 mm Hg. Art. in timolol-tafluprost group and 3-4 mm Hg. Art. in the group timolol-indifferent filler. In a small cross-over study, with a 4-week treatment period, dosage forms with a preservative and no preservative showed a similar IHD-lowering effect - more than 5 mm Hg. Art.

In addition, in a 3-month study in the United States, when compared, the composition 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, whereas the values for timolol varied between 5.3 and 7.5 mm Hg.

Pharmacokinetics:

Absorption

After instillation of eye drops tafluprost, 0.0015% in a dropper tube, no preservative, once a day, one drop in both eyes for 8 days, its plasma concentrations were low and had a similar profile on days 1 and 8. The plasma concentrations reached a maximum 10 minutes after instillation, and decreased to a level lower than the lower detection limit (10 pg / ml) less than one hour after the administration of the drug. The mean values of Stach (26.2 and 26.6 pg / ml) and AUCo-last (394.3 and 431.9 pg / min / ml) were almost the same on days 1 and 8, indicating that during the first week of treatment, a stable concentration of the drug was achieved. Between drug forms with a preservative and without a preservative, no statistically significant differences in systemic bioavailability were found.

In a rabbit study, the absorption of tafluprost into watery moisture, after a single instillation of an ophthalmic solution of tafluprost, 0.0015% with a preservative and no preservative, was comparable.

Distribution

In the monkey study, there was no specific distribution of radiolabeled 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.

Autoradiography in rats showed that the highest concentration of radioactivity was observed in the cornea, followed by eyelids, sclera, and the iris. Systemic radioactivity spread to the tear apparatus, the sky, esophagus, gastrointestinal tract, kidneys, liver, gallbladder and urinary bladder. Binding of tafluprost acid to human serum albumin in vitro is 99% for 500 ng / ml of tafluprost acid.

Biotransformation

The main way of metabolism of tafluprost in the human body, tested in vitro - hydrolysis to form a pharmacologically active metabolite, tafluprost acid, which is then metabolized by glucuronidation or beta oxidation to form pharmacologically inactive 1,2-dinor and 1,2,3,4-tetranor acids of tafluprost that can be glucuronated or hydroxylated. Enzymatic system of cytochrome P450 (CYP) does not participate in the metabolism of tafluprost acid.In a study carried out on rabbit corneal tissues with refined enzymes, it was found that carboxyl esterase is the main esterase responsible for the etheric hydrolysis of tafluprost acid. Butyrylcholinesterase, but not acetylcholinesterase, can also promote hydrolysis.

Excretion

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

Indications:

To reduce increased intraocular pressure in patients with open-angle glaucoma and ophthalmic hypertension. As monotherapy in patients about which shows eye drops that do not contain a preservative about with insufficient response to first-line drugs about who do not tolerate first-line drugs or who have contraindications to these drugs

As an additional therapy to beta-blockers.

Tafluprost is intended for patients over 18 years of age.

Contraindications:

Hypersensitivity to the components of the drug.

Pregnancy and lactation:

Women with childbearing potential / contraception

Women with childbearing potential should not use Taflotan® if they do not use adequate contraception.

Pregnancy

There is 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 / newborn baby. Studies in animals have demonstrated toxic effects on the reproductive system. Therefore, Taflotan® should not be used during pregnancy, unless there are no other treatment options.

Lactation

It is not known whether the tafluprost or its metabolites into human milk. In a study on rats, excretion of tafluprost into breast milk was established after topical application. Therefore, Taflotan® should not be used during breastfeeding.

Fertility

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

Dosing and Administration:

The recommended dose is one drop of eye drops of Taflotan® in the conjunctival sac of the affected eye (eye) once a day, in the evening.

The dose should be installed strictly once a day, as more frequent use can reduce the effect of reducing intraocular pressure.

Only for single use. The contents of one tube-dropper is sufficient for burying in both eyes. The remaining drug should be discarded immediately after use.

Application in elderly patients

In the treatment of elderly patients, there is no need to change the dose.

Application in children and adolescents

The safety and effectiveness of Tafluprost in children and adolescents under the age of 18 years is not established. No data available.

Use in cases of impaired kidney / liver function

Studies on the effects of tafluprost on patients with renal / hepatic disorders have not been conducted, so care should be taken when treating this category of patients.

Method of application

To reduce the risk of darkening the skin of the eyelids, patients should remove excess solution from the skin. As with the application of other eye drops, nasolacrimal occlusion is recommended - soft eyelid closure afterinstillation drug. This can reduce the systemic absorption of medications injected through the eyes.

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

Side effects:

In clinical trials, more than 1,400 patients were treated with tafluprost with a preservative - either as monotherapy, or as an additional drug for treatment with timolol, 0.5%. The most common side effect associated with treatment was eye hyperemia. It was noted in approximately 13% of patients who participated in clinical studies of tafluprost in Europe and the US. In most cases, congestion was moderate, and resulted in discontinuation of treatment on average in 0.4% of patients. In a 3-month phase III study, in the United States, when compared, 0.0015% tufluprost-free formulation with a thymol, as well as without a preservative, eye hyperemia was noted in 4.1% (13/320) of patients who received Tafluprost. The following treatment-related side effects were documented during the clinical trials of Tafluprost in Europe and the US after they were maximally expanded to 24 months:

Ophthalmic

Frequently encountered (from >= 1/100 to <1/10): itchy eyes, eye irritation, eye pain, conjunctiva / eye hyperemia, eyelash changes (increase in length, thickness and number of eyelashes), dry eye syndrome, foreign body sensation in the eyes, eyelid color change, erythema eyelid, superficial pinpoint keratitis, photophobia, increased lacrimation, blurred vision, reduced visual acuity, and increased iris pigmentation.

Infrequent (from >= 1/1000 to <1/100): eyelid pigmentation, eyelid edema, asthenopia, edema of the conjunctiva, the appearance of the discharge from the eyes, blepharitis, anterior chamber inflammation, a feeling of discomfort in the eyes, anterior chamber flax, conjunctival pigmentation, conjunctival follicles, allergic conjunctivitis, and atypical sensation in the eye.

Nervous system disorders

Frequently encountered (from >= 1/100 to <1/10): headache

Skin and subcutaneous tissue disorders

Infrequent (from >= 1/1000 to <1/100): hypertrichosis century.

Overdose:

There were no reports of overdose cases. After the instillation of the drug in the eye, an overdose is unlikely. If an overdose occurs, treatment should be symptomatic.

Interaction:

No cross interactions with other drugs are expected in the treatment of humans, since the concentration of tafluprost in the systemic blood stream, after instillation into the eye, is extremely low, so no special studies have been conducted to study the specific interaction of tafluprost with other drugs.

In clinical trials tafluprost was used concomitantly with timolol, and no signs of cross-interaction were noted.

Special instructions:

Before the treatment, patients should be warned about the possibility of excessive growth of eyelashes, darkening of the skin of the eyelids and increased pigmentation of the iris. Some of these changes can be permanent, and this can lead to differences in the appearance of the eyes, if only one eye was treated.

The change in the pigmentation of the iris occurs slowly, and for several months can remain invisible. Eye color changes are observed mainly in patients with iridescent colors of mixed colors, for example, if the eyes are brownish-blue, gray-brown, yellow-brown or green-brown.Treatment of only one eye can lead to persistent heterochromia.

There is no experience with tafluprost in cases of neovascular, occlusive, narrow-angle or congenital glaucoma. There is only limited experience in the treatment of tafluprost patients with aphakia, pigmentary or pseudoexfoliation glaucoma. It is advisable to use caution in the treatment of tafluprost patients with aphakia, artifics damaged by the posterior lens capsule, or lens implantation in the anterior chamber of the eye, as well as patients with established risk factors for cystoid macular edema or iritis / uveitis.

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

Effect on the ability to drive transp. cf. and fur:

Tafluprost does not affect the ability to drive a car and work with machinery. As with any other ophthalmic products, after instillation of the drug, a brief blurring of vision may occur. In this case, the patient must wait until the vision is fully restored,and only then drive a car or operate a mechanical equipment.

Form release / dosage:

Drops of the eye 0.0015%.

Packaging:

By 0.3 ml per plastic a transparent tube-dropper.

10 tubes of intravenous form of plastic tape, put in packages of laminated aluminum foil.

3, 9 packages together with instruction on medical application is placed in cardboard pack.

Storage conditions:

Store at a temperature of 2 ° C - 8 ° C. After opening the package - at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

After opening the package with a tube-dropper:

- Store the dropper in the bag.

- Eye drops should be stored at a temperature of no higher than 25 ° C.

- After a single use, the tube-dropper should be discarded with the remaining residue.

Shelf life:

3 years

After the first opening of the package - 4 weeks.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002287

Date of registration:28.10.2013

The owner of the registration certificate: Santen, AO Santen, AO Finland

Manufacturer: & nbsp

SANTEN, OY Finland

Representation: & nbspSANTEN AS SANTEN AS Finland

Information update date: & nbsp05.09.2015

Illustrated instructions

Instructions

Taflotan® (Taflotan®)