Composition, form of production and packaging
Eye drops in the form of a clear, colorless solution.
tafluprost 15 mcg
[PRING] 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 / u - up to 1 ml.
0.3 ml - a tube-dropper (10), soldered in the form of a plastic tape - packages from the laminated aluminum foil (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
An antiglaucoma preparation, a fluorinated analogue of prostaglandin F 2? .
Mechanism of action. The acid of tafluprost, being its biologically active metabolite, has a high activity and selectivity for the human FP-prostanoid receptor. The affinity of tafluprost acid for the FP receptor is 12 times higher than the affinity of latanoprost. Pharmacodynamic studies in monkeys have shown that tafluprost reduces intraocular pressure (IOP), enhancing the outgrowth outflow of aqueous humor.
Pharmacodynamic effect. Experiments on monkeys with normal and elevated IOP demonstrated 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% 1 time / day showed that the blood flow in the optic nerve disk significantly (by 15%) increased in comparison with baseline, when measured on days 14 and 28 using a laser speckle-flougraphy.
Clinical effect. Decrease in IOP begins within 2-4 hours after the first installation of the drug, and the maximum effect is reached after about 12 hours. The duration of the effect is maintained for at least 24 hours. Leading studies on the use of tafluprost containing benzalkonium chloride preservative 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, a significant IHD-lowering effect of tafluprost at various time points during the day is shown: from 6 to 8 mm Hg. in comparison with latanoprost, which reduces IOP by 7-9 mm Hg. Art. In another 6-month clinical trial, tafluprost reduced IOP by 5-7 mm Hg. st, and timolol 4-6 mm Hg. Art. 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, a similar IHD-lowering effect of dosage forms with a preservative and no preservative-more than 5 mm Hg-was demonstrated. Art.
In addition, in a 3-month study in the United States, when comparing the tafluprost formulation 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 вЂ‹вЂ‹for timolol varied between 5.3 and 7.5 mm Hg.
After instillation of eye drops, tufluprost 0.0015% in a dropper 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. C max in plasma was reached 10 min after instillation, and decreased to a level lower than the lower detection limit (10 pg / ml) less than 1 h after the administration of the preparation. The mean C max values вЂ‹вЂ‹(26.2 and 26.6 pg / ml) and AUC 0-last (394.3 and 431.9 pg / min / ml) were almost the same on days 1 and 8, indicating that within the first week of treatment, stable concentration of the drug. 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 tufluprost 0.0015% with a preservative and no preservative, was comparable.
The binding of tafluprost acid to human serum albumin in vitro is 99% with an acid concentration of tafluprost 500 ng / ml.
In a monkey study, there was no specific distribution of radioactivity-labeled tafluprost in the iris, ciliary body, or in the choroid, including the retinal pigment epithelium, indicating a low affinity for melanin pigment.
Autoradiography 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 tear apparatus, the sky, esophagus, gastrointestinal tract, kidneys, liver, gallbladder and urinary bladder.
The main way of metabolism of tafluprost in the human body, the tested hydrolysis in vitro 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-tetranoric acids tafluprost, which can be subjected to glucuronisation or hydroxylation. The enzymatic system of cytochrome P450 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.
In a study in rats, after a single instillation of 3 N-tafluprost (0.005% ophthalmic solution, 5 Ојl / eye) in both eyes for 21 days, about 87% of the total radioactive dose was detected in feces. About 27-38% of the total dose was excreted in the urine, with feces about 44-58%.
To reduce the increased intraocular pressure in patients with open-angle glaucoma and ophthalmic hypertension as monotherapy in patients:
- which shows eye drops that do not contain a preservative;
- with insufficient response to first-line drugs;
- Do not tolerate first-line drugs or have contraindications to these drugs.
As an additional therapy to beta-blockers.
Tafluprost is intended for patients over 18 years of age.
The recommended dose is 1 drop of eye drops of Taflotan В® in the conjunctival sac of the affected eye (eye) 1 time / day, in the evening.
The drug in the specified dose should be instilled strictly 1 time / day, tk. more frequent use can reduce the effect of reducing IOP.
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.
In elderly patients, dose adjustment is not required.
The safety and effectiveness of tafluprost in children and adolescents under the age of 18 years is not established, there is no evidence of application.
The efficacy and safety of tafluprost in patients with impaired hepatic and / or renal function have not been studied, therefore caution is required in this category of patients when it is necessary to administer the drug.
Mode 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 - a soft eyelid closure after instillation of the drug. This can reduce systemic absorption of drugs administered through the eyes.
When using several topical ophthalmic drugs, the intervals between their use should be at least 5 minutes.
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 mild and led to discontinuation of treatment on average in 0.4% patients. In a 3-month Phase III study, in the United States, when compared with 0.0015% tufluprost, 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 were documented in the clinical studies of tafluprost in Europe and the US after maximum expansion to 24 months.
From the side of the organ of vision: often (> 1/100 to <1/10) - itching of the eye, eye irritation, eye pain, conjunctival / eye hyperemia, eyelash changes (increase in length, thickness and number of eyelashes), dry eye syndrome, foreign body sensation in the eyes, discoloration of eyelashes, erythema eyelids, superficial pinpoint keratitis, photophobia, increased teardrop, blurred vision, decreased visual acuity, and increased iris pigmentation; infrequently (from> 1/1000 to <1/100) - eyelid pigmentation, eyelid edema, asthenopia, conjunctival edema, 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.
From the nervous system: often (from> 1/100 to <1/10) - headache.
From the skin and subcutaneous tissues: infrequently (from> 1/1000 to <1/100) - hypertrichosis of the eyelids.
- Hypersensitivity to the components of the drug.
PREGNANCY AND LACTATION
Data on the use of tafluprost in pregnant women is not enough. Tafluprost may have an adverse pharmacological effect on the course of pregnancy and / or on the fetus / newborn baby. Therefore, Taflotan В® should not be used during pregnancy, except when there are no other treatment options.
Women of childbearing age should not be prescribed Taflotan В® if they do not use adequate contraception.
It is not known whether tafluprost or its metabolites are excreted in human breast milk. Taflotan В® should not be used during breastfeeding.
In experimental animal studies, toxic effects of tafluprost on the reproductive system have been demonstrated. In a study in rats it was found that after topical application tafluprost is excreted in breast milk. Fertility of female and male rats, mating ability and fertility remained unchanged with the administration of tafluprost up to 100 mcg / kg / day IV.
Before starting treatment, patients should be warned about the possibility of excessive eyelash growth, darkening of the skin of the eyelids, and increased pigmentation of the iris. Some of these changes may 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. The change in eye color is 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.
Caution is advised when treating 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.
Impact on the ability to drive vehicles and manage mechanisms
Tafluprost does not affect the ability to drive vehicles and work with machinery. As with any other ophthalmic device, a short-term blurring of vision may occur after the preparation is installed. In this case, the patient should wait until the vision is fully restored and only then operate the car or work with mechanical equipment.
There were no reports of overdose cases. After the instillation of the drug in the eye, an overdose is unlikely.
Treatment: in case of an overdose, symptomatic therapy is performed.
No cross-reactivity with other drugs is expected in the treatment of humans, since the concentration of tufluprost in the systemic blood stream, after instillation of the drug in the eyes, 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 symptoms of cross-interaction were noted.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children at a temperature of 2 В° to 8 В° C. Shelf life - 3 years.
After opening the package with the tube-droppers stored at a temperature of no higher than 25 В° C. Store the dropper in the bag. Shelf life - 4 weeks.
After a single use, the tube-dropper should be discarded with the remaining residue.