Taptik eye drops 0.0015 + 0.5% 0.3 ml
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Description
Taptik eye drops - a combination drug. Reduces intraocular pressure.
Active ingredients
Timolol
Composition
Active substances: tafluprost, timolol maleate. Excipients: glycerol, disodium hydrogen phosphate, edetate disodium, polysorbate, sodium hydroxide or hydrochloric acid (to adjust the pH), water for injection.
Pharmacological effect
A preparation containing a fixed combination of two active ingredients - tafluprost and timolol. Both active ingredients reduce intraocular pressure (IOP), mutually reinforcing the effects of each other, resulting in the effect of lowering IOP when using the combined drug is more pronounced than the effect of each of the active ingredients separately. Tafluprost is a fluorinated prostaglandin F2α analogue. Tafluprost acid, being a biologically active metabolite of tafluprost, has a high activity and selectivity for human FP receptors (prostaglandin F2α receptors). Data from pharmacodynamic studies (preclinical studies) indicate that tafluprost reduces IOP, enhancing uveoscleral outflow of aqueous humor. Timolola maleate is a non-selective beta-blocker. The exact mechanism of reducing IOP in the application of timolol maleate is currently not fully established, however, the methods of fluorescence and tonography indicate that the main effect may be due to a decrease in the formation of intraocular fluid. At the same time, some studies noted a slight increase in its outflow. It has been shown that in patients with open-angle glaucoma or ocular hypertension and an average IOP before treatment, 24–26 mm Hg. the effect of IOP reduction on the background of the use of the drug Taptikom® was not lower than the effect observed with the combined use of tafluprost 0.0015% and timolol 0.5%, and the decrease in the average daily IOP after 6 months was 8 mm Hg. from the original values. In addition, a comparison was made of the activity of the drug Taptikom® and the corresponding monotherapy drugs in patients with open-angle glaucoma or ophthalmic hypertension and the mean IOP before treatment, which was 26-27 mm Hg. The decrease in the average daily IOP against the background of the use of the drug Taptic® was statistically more significant than that on the background of tafluprost monotherapy, which was used 1 time / day in the morning, or timolol, which was used 2 times / day.After 3 months of treatment, the decrease in mean daily IOP compared with its baseline level in the Taptic group was 9 mmHg. compared with 7 mm Hg observed in both monotherapy groups. The decrease in IOP in those who used Taptic during the day fluctuated between 7 and 9 mm Hg. The combined data from these two clinical studies in patients (n = 168) with initially high IOP of 26 mmHg. or higher showed that in patients treated with Taptik after 3 or 6 months, the average daily decrease in IOP was 10 mm Hg, with a range of 9 to 12 mm Hg. during the day.
Pharmacokinetics
Suction. In the blood plasma of healthy volunteers, the concentrations of tafluprost and timolol acid were determined after a single and repeated use for 8 days of the drug with Taptik in the form of eye drops (1 time / day), as well as tafluprost 0.0015% (1 time / day) and timolol 0.5% (2 times / day). It was found that the Cmax of tafluprost acid in the blood plasma is reached by 10 minutes after the use of the drug by Taptic (Tmax), with its subsequent decrease below the threshold value of the sensitivity of the method (10 pg / ml) for about 30 minutes. The accumulation of tafluprost acid was negligible and on the 8th day of treatment the mean values of AUC0-last (monotherapy: 4.45 ± 2.57 pg × h / ml, Taptik: 3.6 ± 3.7 pg × h / ml) and Cmax (monotherapy: 23.9 ± 11.8 pg / ml, Taptik: 18.7 ± 11.9 pg / ml) were slightly lower when using the drug by Taptik compared to tafluprost monotherapy. The concentration of timolol in the blood plasma after the installation of the drug Taptik on the first and eighth day reached a maximum after 15 minutes and 37.5 minutes (median Tmax), respectively. On the eighth day, the AUC0-last value of timolol (monotherapy: 5750 ± 2440 pg × h / ml, Taptik: 4560 ± 2980 pg × h / ml) and the average Cmax (monotherapy: 1100 ± 550 pg / ml, Taptik: 840 ± 520 pg / ml) were slightly lower with the use of the drug by Taptic than with timolol monotherapy alone. A lower concentration of timolol in the blood plasma when using the drug by Taptic is due to its single use per day, while timolol monotherapy is used 2 times / day. Absorption of tafluprost and timolol through the cornea. Based on the results of preclinical studies, it was found that the penetration of tafluprost from the drug by Taptik through the cornea was comparable to its penetration when using tafluprost in monotherapy 1 time / day, while the penetration of timolol from the drug by Taptik was slightly lower than with timolol monotherapy.The AUC4 value of the tafluprost acid after instillation of the drug with Taptik was 7.5 ng × h / ml and 7.7 ng × h / ml after instillation of the tafluprost monotherapy. The value of AUC4 of timolol after administration of the drug by Taptic and the monotherapy drug was 585 ng × h / ml and 737 ng × h / ml, respectively. Tmax of tafluprost is 60 minutes, both when using the drug by Taptic, and in monotherapy with tafluprost, and Tmax of timolol is 60 minutes when using the preparation by Taptic and 30 minutes in monotherapy with timolol. Distribution. Tafluprost. According to preclinical studies, the distribution of tafluprost labeled with a radioisotope in the tissues of the eye suggests that tafluprost has a low affinity for melanin pigment. An autoradiographic study showed that the highest concentration of radioactivity was observed in the cornea, followed by the eyelids, sclera, and iris. The distribution of radioactively-labeled tafluprost in other organs was as follows: lacrimal apparatus, palate, esophagus, gastrointestinal tract, kidneys, liver, gall bladder. The binding of tafluprost acid to human serum albumin in vitro was 99% at a concentration of 500 ng / ml of tafluprost acid. Timolol. According to preclinical studies, Cmax of timolol with a radioactive label in aqueous humor is achieved 30 minutes after a single application of timolol containing the radioactive 3H isotope (0.5% solution: 20 μl / eye). Timolol is derived from aqueous humor much faster than from the pigment-containing tissues of the iris and ciliary body. Metabolism. Tafluprost. The main metabolic pathway for tafluprost in the human body, confirmed by in vitro studies, is hydrolysis to form a pharmacologically active metabolite, tafluprost acid, which is then metabolized by glucuronidation or beta-oxidation. The beta-oxidation products are pharmacologically inactive 1,2-dinor and 1,2,3,4-tetranor tafluprost acid, which can be glucuronidated or hydroxylated. The cytochrome P450 enzyme system is not involved in the metabolism of tafluprost acid. In a study conducted on rabbit cornea tissues with refined enzymes, it was found that carboxylesterase is the main esterase responsible for the ester hydrolysis of tafluprost to tafluprost acid. Butyrylcholinesterase can also promote hydrolysis. Timolol.Timolol is metabolized in the liver with the participation of CYP2D6 isoenzyme of cytochrome P450 with the formation of inactive metabolites, which are excreted mainly by the kidneys. Excretion. Tafluprost. In a study on rats, it was found that after instillation of 3H-tafluprost in the form of a 0.005% ophthalmic solution into both eyes once a day for 21 days, about 87% of the total radioactive dose is excreted through the excretory organs. Approximately 27-38% of the total dose was excreted by the kidneys, and about 44-58% through the gastrointestinal tract. Timolol. The expected T1 / 2 from plasma is about 4 hours. After oral administration, timolol is gradually metabolized in the liver, metabolites are excreted in the urine along with 20% unchanged timolol. Data on the removal of timolol obtained by its oral administration.
Indications
IOP reduction in adult patients with open-angle glaucoma or intraocular hypertension with insufficient response to local monotherapy with beta-adrenergic blocking agents or prostaglandin analogs in cases where combination therapy is indicated, as well as in patients who are expected to improve treatment tolerance through the use of ophthalmic no preservative free drops.
Contraindications
Syndrome of increased reactivity of the respiratory tract, including bronchial asthma or history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, SSS, sinoatrial block, AV block II and III without a pacemaker, decompensated heart failure, cardiogenic shock, age up to 18 years ( no data of clinical use), pregnancy, breastfeeding, hypersensitivity to tafluprost, timolol or any of the components of the drug.
Precautionary measures
The drug should be used with caution (due to limited experience) in patients with hepatic and renal insufficiency, with aphakia, pseudophakia with rupture of the posterior lens capsule or lens implantation in the anterior chamber of the eye, pseudoexfoliative glaucoma, and also in patients with established factors risk of developing cystoid macular edema or iritis / uveitis, with neovascular, angle-closure, narrow-angle and congenital glaucoma (there is no experience with tafluprost),in patients with corneal diseases (can cause dry eye syndrome), cardiovascular diseases (IHD, Prinzmetal angina pectoris, heart failure, AV degree I blockade), in disorders of the peripheral circulation (in severe forms of Raynaud’s disease or Raynaud’s syndrome), COPD mild and moderate (use of the drug is possible only if the expected benefit outweighs the potential risk), in patients with a labile course of diabetes mellitus or spontaneous hypoglycemia (because beta-blockers can mask develop clinical signs and symptoms of acute hypoglycemia), concomitant treatment with beta-blockers (when taken orally and in the form of ophthalmic).
Use during pregnancy and lactation
Pregnancy. There are no adequate data on the use of the drug by Taptic in pregnant women. Women of childbearing age need to use effective methods of contraception during treatment with the drug Taptik. Do not use the drug Taptik during pregnancy, except in special cases (if there are no other methods of treatment). Tafluprost. There are no adequate data on the use of tafluprost in pregnant women. Tafluprost may have an adverse pharmacological effect on the course of pregnancy and / or on the development of the fetus or newborn child. In animal studies there is evidence of reproductive toxicity of tafluprost, while at the same time, the potential risk of its use in humans is unknown. Timolol. Adequate data on the use of timolol in pregnant women are not available. The test should not be used in pregnant women, unless the expected benefit to the mother outweighs the potential risk to the fetus. Information on measures to reduce systemic absorption is presented in the section “Dosing regimen.” In epidemiological studies no systemic abnormalities in the development of the fetus were detected, but there was a risk of intrauterine growth retardation in case of taking beta-blockers orally. In addition, the clinical manifestations and symptoms of β-adrenoreceptor blockade (for example, bradycardia, hypotension, respiratory disorders and hypoglycemia) were observed in newborns if beta-blockers were used before delivery.In the case of the use of the drug Taptik® before delivery, you should carefully monitor the condition of the newborn during the first days of life. Breastfeeding. It is known that beta-blockers penetrate into breast milk. However, it is unlikely that when using timolol in the composition of the eye drops at the recommended therapeutic doses, sufficient quantities of the substance can penetrate into breast milk in order to cause symptoms of β-adrenoreceptor blockade in an infant. Information on measures to reduce systemic absorption is presented in the section “Dosing regimen”. There is no data on the excretion of tafluprost or its metabolites in human breast milk. Available toxicological data in animals indicate a possible excretion of tafluprost and its metabolites into breast milk. However, it is unlikely that when using tafluprost as part of eye drops at the recommended therapeutic doses, sufficient amounts of the substance will be absorbed into breast milk to cause clinical symptoms in an infant. As a precautionary measure, breastfeeding of infants is not recommended if the mother requires therapy with the drug Taptik. Fertility. There are no data on the effect of drug Taptik on fertility (fertility) in humans.
Dosage and administration
The drug is intended only for ophthalmic use. The recommended dose is 1 drop of the drug Taptik in the conjunctival sac of the affected eye (s) 1 time / day. The dose should not exceed 1 drop in the affected eye (eyes) / day, since more frequent use of the drug can reduce the expected effect of lowering IOP. If one dose is missed, treatment is continued with the next scheduled dose. Taptikom is a sterile solution containing no preservatives, packaged in disposable tubes, droppers. The solution in one tube-dropper is intended for single use only, and its amount is sufficient for use in both eyes. The use of the drug Taptikom in children and adolescents under the age of 18 years is not recommended. Elderly patients do not require dose adjustment of the drug. The use of the drug by Taptic has not been studied in patients with renal and hepatic insufficiency; therefore, it is necessary to use the drug in such patients with caution. Mode of application. To reduce the risk of darkening of the eyelid skin, patients should remove excess solution from the skin.As with the use of other eye drops, with short-term finger pressing of the nasolacrimal canals or closing of the eyelids for 2 minutes after application, there is a decrease in systemic absorption of the drug. Such a measure reduces the risk of systemic side effects and enhances the local effect of the drug. When using several local ophthalmic drugs, the intervals between their use should be at least 5 minutes. Before using the drug contact lenses must be removed and re-installed after 15 minutes. Patients should be warned not to touch the eye and the surrounding tissue with the tip of a dropper tube, as this may cause damage to them.
Side effects
In the framework of clinical studies, more than 484 patients received treatment with the drug Taptik. The most commonly reported side effect associated with the treatment, which occurred in approximately 7% of patients, was conjunctival / eye hyperemia, in most cases mild. The undesirable reactions observed in clinical trials of the drug Taptik were limited to the same reactions that were previously observed with the separate use of tafluprost and timolol. New undesirable reactions characteristic only for the drug Taptik in clinical studies have not been identified. The majority of undesirable reactions were observed on the part of the organ of vision, had a mild or moderate degree; no serious reactions were noted. According to MedDRA terminology, the following classification was used to estimate the frequency of undesirable reactions: very often (≥1 / 10 cases), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10,000, <1/1000), very rarely (<1/10 000) and unknown (the frequency cannot be determined from the available data). Tampic (combination of tafluprost and timolol). Co side of the nervous system: infrequently - a headache. On the part of the organ of vision: often - conjunctival hyperaemia / eyes, itchy eyes, eye pain, eyelash changes (increase in length, thickness and number of eyelashes), change in eyelash color, eye irritation, foreign body sensation, blurred vision, photophobia, infrequently - discomfort in the eye area, dry mucous membranes of the eyes, discomfort in the eyes, conjunctivitis, erythema of the eyelids, symptoms of allergic eye damage, eyelid edema, superficial punctate keratitis, watery eyes, an inflammatory reaction in the anterior chamber moisture, and tenopiya, blepharitis.The adverse reactions that were observed during the period of treatment with tafluprost or timolol, and which can potentially develop with the use of the drug Tiptik, are presented below. Tafluprost. On the part of the organ of vision: reduced visual acuity, increased pigmentation of the iris, pigmentation of the eyelids, swelling of the conjunctiva, appearance of discharge from the eyes, cellular opalescence in the anterior chamber of the eye, allergic conjunctivitis, pigmentation of the conjunctiva, conjunctival follicles, deepening of the eyelid fold, iritis / uveitis. From the skin and subcutaneous tissues: eyelid hypertrichosis. On the part of the respiratory system: unknown - exacerbation of asthma, shortness of breath. Timolol. On the part of the immune system: allergic reactions, including angioedema, urticaria, local or generalized skin rash, anaphylaxis, pruritus. Metabolism: hypoglycemia. Mental disorders: depression, insomnia, nightmares, memory loss, nervousness. On the part of the nervous system: dizziness, fainting, paresthesia, increased symptoms of myasthenia, acute cerebrovascular accident, cerebral ischemia. On the part of the organ of vision: keratitis, decreased corneal sensitivity, impaired visual acuity, including refractive changes (in some cases as a result of withdrawal of miotic therapy), ptosis, diplopia, choroidal detachment after fistulatory surgery, tearing, corneal erosion. On the part of the organ of hearing and balance: ringing in the ears. Since the cardiovascular system: bradycardia, chest pain, palpitations, edema, arrhythmia, congestive heart failure, cardiac arrest, heart block, AV blockade, heart failure, decreased blood pressure, intermittent claudication, Raynaud's phenomenon, cold hands and feet . On the part of the respiratory system: dyspnea, bronchospasm (mainly in patients with a history of indicating a bronchospastic disease), respiratory failure, cough. On the part of the digestive system: nausea, dyspepsia, diarrhea, dryness of the oral mucosa, dysgeusia, abdominal pain, vomiting. From the skin and subcutaneous tissues: alopecia, psoriasis-like rash or exacerbation of the course of psoriasis, skin rash. On the part of the musculoskeletal system: systemic lupus erythematosus, myalgia, arthropathy.On the part of the reproductive system and the breast: Peyronie's disease, decreased libido, sexual dysfunction. General disorders: asthenia / fatigue, thirst. Very rarely when using eye drops containing phosphates, cases of corneal calcification have been reported in some patients with severe corneal damage.
Overdose
Cases of drug overdose Taptik were reported. When instilled into the eye, overdose symptoms are unlikely. Symptoms: there were reports of an unintentional overdose of timolol, which led to the development of systemic effects similar to those in the systemic use of beta-blockers, namely, dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest. Treatment: if overdose symptoms occur with the use of the drug Taptik, it is necessary to carry out symptomatic and supportive therapy. The removal of timolol in hemodialysis is slow.
Interaction with other drugs
Clinical studies on the interaction of the drug were not conducted. Possible reduction in blood pressure and / or the appearance of clinically pronounced bradycardia in the case of simultaneous use of ophthalmic drugs containing beta-blockers, and systemic use of slow calcium channel blockers, other beta-blockers, antiarrhythmic drugs (including amiodarone), cardiac glycosides, parasympathomimetics, guanethidine. Acceptance of beta-adrenergic blockers inside can lead to increased ricochet hypertension, observed with the withdrawal of clonidine. With simultaneous use of inhibitors of the isoenzyme CYP2D6 (for example, quinidine, fluoxetine, paroxetine) and timolol, an increase in the systemic action of a beta-blocker (decrease in heart rate, depression) has been reported. With the simultaneous use of ophthalmic drugs containing beta-blockers and adrenaline (epinephrine), in some cases, pupil dilation was noted.
special instructions
System effects Like other ophthalmic drugs, tafluprost and timolol are absorbed systemically. Due to the presence of a beta-adrenergic component of timolol in the preparation, the same undesirable reactions from the cardiovascular system and respiratory organs can develop as with the use of systemic beta-blockers. The incidence of systemic adverse reactions after topical application of eye drops is lower than after systemic administration.Information on measures to reduce systemic absorption is presented in the section "Dosing regimen." Violations of the heart. In patients with cardiovascular diseases (eg, coronary artery disease, Prinzmetal angina, heart failure) and arterial hypotension, it is necessary to carefully assess the need for therapy with beta-blockers and consider the possibility of using other groups of drugs. It is necessary to monitor the condition of patients with cardiovascular diseases in order to timely identify the symptoms of worsening diseases and adverse reactions. Due to its negative effect on the speed of the impulse, beta-blockers should be used with caution in patients with AV-blockade grade I. Violations of the vessels. It is necessary to use the drug with caution in patients with severe impairment of the peripheral circulation (for example, severe forms of Raynaud's disease or Raynaud's syndrome). Violations of the respiratory organs. After using some ophthalmic beta-blockers, the risk of unwanted reactions from the respiratory organs, including deaths due to bronchospasm in patients with bronchial asthma, may increase. In patients with mild / moderate degree of COPD, TAPTIC should be used with caution and only if the expected benefit of its use outweighs the possible risk. Hypoglycemia / diabetes mellitus. Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia, or in patients with a labile course of diabetes, because beta-blockers may mask the signs and symptoms of acute hypoglycemia. Hyperthyroidism. Beta-blockers can also mask signs of hyperthyroidism. Abrupt cancellation of therapy with beta-blockers can lead to worsening of the symptoms of the disease. Corneal diseases. Ophthalmic beta-blockers may contribute to the development of dry eye syndrome. Caution must be exercised when using the drug in patients with corneal diseases. Other beta-blockers. The effect on intraocular pressure or the known effects of systemic blockade of β-adrenoreceptors may be enhanced by the use of timolol (one of the active ingredients of the drug Taptik) in patients already receiving systemic beta-blocker. The condition of such patients should be carefully monitored.It is not recommended to use two local beta-blockers simultaneously. Close-angle glaucoma. In patients with angle-closure glaucoma, the primary goal of therapy is to open the anterior chamber angle of the eye. This requires the constriction of the pupil with a miotic preparation. Timolol has minimal or no effect on the pupil. When timolol is used to reduce elevated intraocular pressure with angle-closure glaucoma, it should be used in combination with miotics, and not as monotherapy. Anaphylactic reactions. When using beta-adrenergic blockers, patients with atopic history or a severe anaphylactic reaction to a number of allergens in the history may react more strongly to the repeated administration of such allergens and not to respond to the usual doses of adrenaline used to treat anaphylactic reactions. Delamination of the vascular membrane. Cases of detachment of the choroid have been reported when using drugs that suppress the production of aqueous humor (for example, timolol, acetazolamide) after fistulatory operations. General anesthesia. Ophthalmic beta-blockers can block the effects of systemic β-adrenoreceptor agonists, such as adrenaline. The anesthetist should be informed about the patient's use of timolol. Prior to treatment, patients should be informed about the possible excessive growth of eyelashes, darkening of the eyelid skin and increased iris pigmentation, which are associated with tafluprost therapy. Some of these changes may be permanent, and this can lead to differences in the appearance of the eye, if only one eye has been treated. The change in pigmentation of the iris occurs slowly and may remain imperceptible for several months. The change in eye color is observed mainly in patients with iris of mixed colors, for example, if the eyes are brown-blue, gray-brown, yellow-brown or green-brown. Treatment of only one eye can lead to persistent heterochromia. If the rules for storage of ophthalmic drugs are not followed, their bacterial contamination is possible, which can lead to the development of bacterial infections of the organ of vision, which can potentially lead to significant visual impairment or loss. Impact on driving ability and control mechanisms. The effect of the drug Taptik on the ability to drive and work with mechanisms has not been studied.As with the use of any other ophthalmologic agents, after using the drug, a short-term blurring of vision may occur, so it is necessary to refrain from driving and performing activities that require increased concentration of attention and psychomotor speed, before restoring vision.