Instructions for use Taflotan eye drops 15 mcg/ml bottle 2.5 ml
Composition
active ingredient: tafluprost;
1 ml of eye drops contains 15 mcg of tafluprost;
1 bottle (2.5 ml) of eye drops contains 37.5 mcg of tafluprost;
Excipients: benzalkonium chloride; glycerin; sodium dihydrogen phosphate, dihydrate; disodium edetate; polysorbate-80; sodium hydroxide or concentrated hydrochloric acid; water for injections.
Dosage form
Eye drops.
Main physicochemical properties: transparent, colorless solution. Contains no visible particles.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Prostaglandin analogues. Tafluprost.
ATX code S01E E05.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Tafluprost is a fluorogenic analogue of prostaglandin F2α. Tafluprost acid, the biologically active metabolite of tafluprost, is a highly potent and selective agonist of the human prostanoid FP receptor. Tafluprost acid has 12 times greater affinity for the FP receptor than latanoprost. Pharmacodynamic studies in monkeys indicate that tafluprost reduces intraocular pressure by increasing uveoscleral outflow of aqueous humor.
Pharmacodynamic effects
Tafluprost is a substance that effectively reduces intraocular pressure. In a study that examined the effect of tafluprost metabolites on reducing intraocular pressure, only tafluprost acid resulted in a significant reduction in intraocular pressure.
When rabbits were treated with tafluprost ophthalmic solution 0.0015% once daily for 4 weeks, optic disc blood flow increased significantly (15%) from baseline when measured by laser speckle flowgraphy on days 14 and 28.
Clinical efficacy
The reduction in intraocular pressure begins 2-4 hours after the first administration of the drug, and the maximum effect is achieved approximately 12 hours after instillation. The duration of the effect is maintained for at least 24 hours.
Basic studies of tafluprost, which contains the preservative benzalkonium chloride, have demonstrated the efficacy of tafluprost as a monotherapy and its additive effect when administered as an adjunct to timolol treatment.
In a 6-month study, tafluprost was shown to significantly reduce intraocular pressure by 6–8 mmHg when administered at different times of the day, compared with 7–9 mmHg with latanoprost. In another 6-month clinical study, tafluprost reduced intraocular pressure by 5–7 mmHg compared with 4–6 mmHg with timolol. The IOP-lowering effect of tafluprost was maintained when these studies were continued for up to 12 months. A 6-week study compared the IOP-lowering effects of tafluprost and its excipient when administered concomitantly with timolol. Compared with baseline values (measured after a 4-week initial course of timolol), the additional IOP-lowering effect was 5–6 mmHg in the timolol-tafluprost group and 3–4 mmHg in the timolol-vehicle control group. Tafluprost formulations with and without added preservative had similar effects in reducing IOP by more than 5 mmHg in a small crossover study with a 4-week treatment period. Furthermore, in a 3-month study conducted in the United States comparing tafluprost without added preservative with timolol without added preservative, the IOP-lowering effect of tafluprost ranged from 6.2 to 7.4 mmHg at different time points, whereas the effect of timolol ranged from 5.3 to 7.5 mmHg.
Pharmacokinetics
Absorption
After a single intraocular administration of one drop of tafluprost, 0.0015% eye drops, to each eye once daily for 8 days, plasma concentrations of tafluprost acid were low and had similar profiles on days 1 and 8. Plasma concentrations peaked 10 minutes after administration and declined to below the lower limit of detection (10 pg/mL) by the end of the first hour after administration. Mean Cmax (24.4 and 31.4 pg/mL) and AUC0-last (area under the concentration-time curve from the time of administration to the last quantifiable concentration) (405.9 and 581.1 pg*min/mL) were similar on days 1 and 8, indicating that steady-state drug concentrations were achieved within the first week after intraocular administration. No statistically significant differences in systemic bioavailability were found between the preservative-containing and preservative-free formulations.
In a rabbit study, the absorption of tafluprost into the intraocular fluid was comparable after a single instillation of tafluprost, 0.0015% eye drops, without or with preservative.
In monkeys, no significant distribution of radiolabeled tafluprost was observed in the iris-ciliary body or choroid, including the retinal pigment epithelium, indicating a low affinity for the pigment melanin. In a whole-body autoradiography study in rats, the highest radioactivity concentrations were observed in descending order in the cornea, eyelids, sclera and iris. Outside the eye, radioactivity was distributed in the lacrimal apparatus, palate, esophagus and gastrointestinal tract, kidneys, liver, gallbladder and urinary bladder.
The binding of tafluprost acid to human serum albumin in vitro was 99% when tafluprost acid was used at 500 ng/mL.
Biotransformation
The main metabolic pathway of tafluprost in humans, which has been analyzed in vitro, is hydrolysis of the pharmacologically active metabolite, tafluprost acid, which is further metabolized by glucuronidation or beta-oxidation. The beta-oxidation products, 1,2-dinor- and 1,2,3,4-tetranor-tafluprost acid, which are pharmacologically inactive, may undergo glucuronidation or hydroxylation. The cytochrome P450 (CYP) enzyme system is not involved in the metabolism of tafluprost acid. Based on data from studies on rabbit corneal tissues and using purified enzymes, the main esterase responsible for the hydrolysis of the ester to tafluprost acid is carboxylesterase. Butylcholinesterase, but not acetylcholinesterase, may also participate in the hydrolysis.
Breeding
After once-daily administration of 3H-tafluprost (0.005% ophthalmic solution; 5 μl/eye) to rats in both eyes for 21 days, approximately 87% of the total radioactive dose was excreted from the body. The proportion of the total dose excreted in the urine was approximately 27-38%, and approximately 44-58% of the dose was excreted in the feces.
Indication
Reduction of elevated intraocular pressure in open-angle glaucoma and ocular hypertension in adults.
It is used as monotherapy in patients:
with insufficient response to first-line treatment; with intolerance or contraindications to first-line treatment.
As an additional treatment in combination with beta-blockers.
Contraindication
Hypersensitivity to the active substance tafluprost or to any of the excipients.
Interaction with other medicinal products and other types of interactions
Interactions in humans are not expected because systemic concentrations of tafluprost after intraocular administration are very low. Therefore, specific drug interaction studies with tafluprost have not been conducted.
In clinical studies, tafluprost was used concomitantly with timolol without any evidence of interaction.
Application features
Before starting treatment, patients should be informed of the possible growth of eyelashes, darkening of the eyelid skin, and increased pigmentation of the iris. Some of these changes may be permanent and may result in differences in appearance between eyes if only one eye is treated.
The change in iris pigmentation occurs gradually and may not be noticeable for several months. The change in eye color has mainly been observed in patients with mixed-colored irises, such as blue-brown, gray-brown, yellow-brown, and green-brown. There is a risk of lifelong heterochromia of the eyes if only one eye is treated.
There is a potential for hair growth in areas where tafluprost solution has repeatedly come into contact with the skin surface.
There is no experience with the use of tafluprost in neovascular, angle-closure, narrow-angle or congenital glaucoma. There is only limited experience with the use of tafluprost in the treatment of aphakic patients and in pigmentary or pseudoexfoliative glaucoma.
It is recommended that tafluprost be used with caution in patients with aphakia, pseudophakia with rupture of the posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular edema or iritis/uveitis.
There is no experience with the use of the drug in patients with severe asthma. Therefore, the drug should be used with caution in such patients.
Benzalkonium chloride, commonly used as a preservative in ophthalmic preparations, has been reported to cause punctate keratitis and/or toxic ulcerative keratitis. As the product contains benzalkonium chloride, close monitoring is necessary with frequent or prolonged use in patients with dry eye syndrome or conditions characterized by corneal damage.
The product contains benzalkonium chloride, which may cause eye irritation. Avoid contact with soft contact lenses. Remove contact lenses before instilling the product and wait at least 15 minutes before reinserting them. Benzalkonium chloride is known to discolour soft contact lenses.
Ability to influence reaction speed when driving vehicles or other mechanisms
Tafluprost does not affect the ability to drive or use machines. As with any intraocular medication, if temporary blurred vision occurs after instillation, the patient should wait until vision clears before driving or using machines.
Use during pregnancy or breastfeeding
Women of reproductive age/contraception
The drug should not be used in women of reproductive age who are not using adequate contraception.
Pregnancy
There are no adequate data from the use of tafluprost in pregnant women. Tafluprost may have adverse pharmacological effects on pregnancy and/or the fetus/newborn. Animal studies have shown reproductive toxicity. Therefore, the drug should not be used during pregnancy unless clearly necessary (if no other treatment options are available).
Breast-feeding
It is not known whether tafluprost or its metabolites are excreted in human milk. Studies in rats have shown excretion of tafluprost and/or its metabolites in human milk after topical administration. Therefore, tafluprost should not be used during breastfeeding.
Fertility
In rats, intravenous administration of tafluprost at doses up to 100 mcg/kg/day had no effect on mating ability and fertility.
Method of administration and doses
Dosage
The recommended dose is 1 drop of the drug into the conjunctival sac of the affected eye(s) once a day, in the evening.
It is not recommended to administer the drug more often than once a day, as more frequent administration may reduce the effect of lowering intraocular pressure.
Use in elderly patients
No dose adjustment is required for elderly patients.
Use in patients with renal/hepatic impairment
Tafluprost has not been studied in patients with renal/hepatic impairment, therefore it should be used with caution in the treatment of such patients.
Method of application
To prevent potential contamination of the solution, patients should not touch their eyelids, surrounding areas, or any other surfaces with the dropper tip of the bottle.
To reduce the risk of darkening of the eyelid skin, patients should wipe excess solution from the skin. As with any other eye drops, it is recommended to occlude the nasolacrimal ducts or lightly cover the eyelids after instillation. This may reduce the systemic absorption of intraocularly administered drugs.
If a patient is using more than one topical ophthalmic medication, the intervals between administration of each medication should be at least 5 minutes.
Children
The safety and efficacy of tafluprost in children (under 18 years of age) have not been established. Data are not available.
Overdose
Overdose in the case of intraocular administration is unlikely. In case of overdose, treatment is symptomatic.
Adverse reactions
In clinical trials, over 1400 patients were treated with tafluprost as monotherapy or as adjunctive therapy to timolol 0.5%. The most common treatment-related adverse reaction was ocular hyperemia. It occurred in approximately 13% of patients in clinical trials of tafluprost in Europe and the United States. In most cases, ocular hyperemia was mild and led to discontinuation of the drug in an average of only 0.4% of patients in the pivotal trials.
The following treatment-related adverse reactions were observed in clinical trials of tafluprost in Europe and the USA with a maximum follow-up period of 24 months.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Frequency is defined as:
very common (≥ 1/10), common (≥ 1/100 - <1/10), uncommon (≥ 1/1000 - <1/100), rare (≥1/10000 - <1/1000), unknown (cannot be determined from the available data).
Nervous system disorders
Common (≥ 1/100 to < 1/10): headache.
Visual impairment
Very common (≥ 1/10): conjunctival/ocular hyperemia.
Common (≥ 1/100 to < 1/10): eye itching, eye irritation, eye pain, eyelash changes (increased length, thickness and number of eyelashes), dry eye syndrome, foreign body sensation in the eye, eyelash discoloration, eyelid redness, superficial punctate keratitis (SPK), photophobia, increased lacrimation, blurred vision, reduced visual acuity and increased iris pigmentation.
Uncommon (≥ 1/1,000 to < 1/100): eyelid pigmentation, eyelid edema, asthenopia (rapid eye fatigue), conjunctival edema, eye discharge, blepharitis, anterior chamber cell disorder, ocular discomfort, anterior chamber hyperemia, conjunctival pigmentation, conjunctival follicles, allergic conjunctivitis, and abnormal ocular sensation.
Not known (frequency cannot be estimated from the available data): iritis/uveitis, deepening of the palpebral fissure, macular edema/cystic macular edema.
In some patients with significant corneal damage, cases of corneal calcification have been very rarely observed in association with the use of eye drops containing phosphates.
Not known (frequency cannot be estimated from the available data): asthma exacerbation, difficulty breathing.
Skin and subcutaneous tissue disorders
Uncommon (≥ 1/1,000 to < 1/100): hypertrichosis of the eyelids.
Reporting of suspected adverse reactions
It is important to report suspected adverse reactions after a medicinal product has been registered. This allows the benefit/risk balance of the medicinal product to be monitored. Healthcare professionals are asked to report any suspected adverse reactions.
Expiration date
3 years.
Use within 4 weeks after opening the bottle.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
2.5 ml in a bottle. 1 bottle with a dropper tip and cap in a cardboard box.
Vacation category
According to the recipe.
Producer
Santen Oy.
Location of the manufacturer and its business address
Niittyhaankatu 20, 33720 Tampere, Finland.
