Tisoptan drops 0.3 + 5mg / ml, 3ml
Expiration Date: 05/2027
Russian Pharmacy name:
Тизоптан капли 0,3+5мг/мл, 3мл
Recommended doses in adults (including elderly patients)
One drop is instilled into the conjunctival sac of the affected eye 1 time per day in the morning or in the evening. The drug should be used daily at the same time. The available literature data for bimatoprost + timolol suggests that the evening dose may be more effective in lowering IOP than the morning dose. However, you should consider the possibility of following the selected mode. If the administration of the drug is missed once, the drug is administered the next day.
It is not recommended to exceed the dose - 1 injection once a day. If more than 2 drugs are used, it is necessary to take a 5-minute break between each instillation. By pressing on the area of ??the nasolacrimal canal or closing the eyelids for 2 minutes, systemic absorption is reduced, which can lead to a decrease in side effects and an increase in local exposure.
1 ml of the drug contains:
active ingredients: bimatoprost 0.3 mg, timolol maleate 6.83 mg (equivalent to timolol 5 mg); excipients: benzalkonium chloride 0.05 mg, citric acid monohydrate 0.14 mg, sodium hydrogen phosphate heptahydrate 2.68 mg, sodium chloride 6.8 mg, sodium hydroxide to pH 7.3, hydrochloric acid to pH 7.3, water for injection up to 1 ml.
Hypersensitivity to the components of the drug;
Syndrome of increased airway reactivity, including bronchial asthma in the acute stage and previous episodes in history, severe chronic obstructive pulmonary disease (COPD);
Sinus bradycardia, sick sinus syndrome, sinoauricular block, II and III degree atrioventricular block without an implanted artificial pacemaker, clinically expressed heart failure, cardiogenic shock;
Age under 18.
Pharmacotherapeutic group : combined antiglaucoma agent (prostaglandin F2-alpha synthetic analogue + beta-blocker).
Pharmacodynamics
TisoptanЃ is a combined drug containing bimatoprost and timolol that reduce intraocular pressure (IOP) due to combined interaction, leading to a significantly more pronounced hypotensive effect compared to the effect of each of the components separately. Bimatoprost belongs to synthetic prostamides, its chemical structure is similar to prostaglandin F2? (PGF2?). Bimatoprost does not affect any of the known types of prostaglandin receptors. The hypotensive effect of bimatoprost is carried out by increasing the outflow of intraocular fluid through the trabecula and along the uveoscleral pathway of the eye. Timolol is a non-selective beta-blocker that does not have internal sympathomimetic and membrane-stabilizing activity. Timolol reduces IOP by reducing the formation of intraocular fluid.The exact mechanism of action has not been established, perhaps it is associated with inhibition of the synthesis of cyclic adenosine monophosphate (c-AMP) and is caused by endogenous stimulation of beta-adrenergic receptors.
Pharmacokinetics
TizoptanЃ Systemic absorption of the drug is minimal, it does not differ both in combination treatment and in the instillation of each of the components of the drug separately. In two studies lasting 12 months, there was no systemic cumulation of any of the active ingredients. Bimatoprost In vitro studies have shown that bimatoprost penetrates the iris and sclera. When instilling a 0.03% solution of bimatoprost, 1 drop in both eyes once a day for 2 weeks, the maximum concentration (Cmax) of bimatoprost in blood plasma is reached within 10 minutes after application, and within 1.5 hours its concentration in plasma blood decreases to the lower limit of detection (0.025 ng / ml), the mean Cmax and area under the concentration-time curve (AUC0-24h) of bimatoprost were close on days 7 and 14 of use, and were 0,08 ng / ml and 0.09 ng * h / ml, respectively, indicating that the equilibrium concentration of bimatoprost is achieved during the first week of use. Bimatoprost is moderately distributed in tissues, and the systemic volume of distribution when the equilibrium concentration of the drug is reached is 0.67 l / kg. Bimatoprost is found mainly in blood plasma. The connection of bimatoprost with blood plasma proteins is approximately 88%. Bimatoprost undergoes oxidation, N-deethylation and glucuronidation to form various metabolites. Bimatoprost is excreted primarily by the kidneys. About 67% of the drug administered intravenously to healthy volunteers was excreted in the urine, and 25% through the gastrointestinal tract (GIT). The half-life (T1 / 2) of bimatoprost, determined after its intravenous administration, was approximately 45 minutes; and the total clearance is 1,5 l / h / kg. In elderly patients: When using bimatoprost 2 times a day, the average value (AUC0-24 h) in elderly patients is 0.0634 ng * h / ml, which significantly exceeds the value of this indicator in healthy young people - 0.0218 ng * h / ml. Nevertheless, this difference has no clinical significance, since the systemic exposure of bimatoprost with its topical application in elderly patients and healthy young people remains very low. Cumulation of bimatoprost in the systemic circulation is not observed, the safety profile does not differ in elderly patients and young people. Timolol In patients who underwent surgical treatment of cataracts, after instillation of eye drops in the form of a 0.5% solution, the Cmax of timolol in the intraocular fluid after 1 hour was 898 ng / ml.A certain amount of the drug enters the systemic circulation and is metabolized in the liver. T1 / 2 of timolol is about 4-6 hours. Part of timolol metabolized in the liver is excreted through the gastrointestinal tract, and the other part and metabolites are excreted by the kidneys. Timolol binds to a small extent with blood plasma proteins.
Application during pregnancy and during breastfeeding
There are no adequate data on the use of the fixed combination bimatoprost / timolol in pregnant women. TisoptanЃ during pregnancy should be used only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. Adequate and strictly controlled studies of the combination of bimatoprost + timolol in pregnant women have not been conducted. In animal studies, data were obtained on reproductive toxicity at high doses of bimatoprost. Epidemiological studies did not reveal congenital malformations of the fetus, but they established the risk of intrauterine growth retardation when taking drugs from the group of beta-blockers orally. In cases where the patients took a beta-blocker before delivery, the newborns showed clinical symptoms characteristic of this group of drugs (for example,bradycardia, hypotension, respiratory distress syndrome, and hypoglycemia). In the case of using the drug TisoptanЃ until delivery, it is necessary to monitor the condition of the newborn during the first days of life. In animal studies, the reproductive toxicity of timolol has been shown when using doses significantly higher than those prescribed in clinical practice. Thus, TisoptanЃ is not recommended for use during pregnancy, except in cases of special need. Beta blockers pass into breast milk. However, when using timolol in the form of eye drops in therapeutic doses, the development of clinical symptoms in children is unlikely, due to the lack of a sufficient amount of the drug in breast milk. It is not known whether bimatoprost passes into human breast milk, but it has been established that it is found in the milk of lactating rats.TisoptanЃ should not be used in women during breastfeeding.
Side effect
Immune system disorders: Frequency unknown: hypersensitivity reactions, including signs or symptoms of allergic dermatitis, angioedema, allergic eye reactions. Mental disorders: frequency unknown: insomnia, nightmares. Nervous system disorders: often: headache, dizziness; frequency unknown: dysgeusia. Violations of the organ of vision: very often: conjunctival hyperemia; often: punctate keratitis, corneal erosion, burning sensation, itchy eyes, tingling sensations in the eyes, foreign body sensation, dry eyes, redness of the eyelids, eye pain, photophobia, eye discharge; infrequently: iridocyclitis, conjunctival edema, soreness of the eyelids, asthenopia, trichiasis, iris hyperpigmentation, deepening of the eyelid fold, eyelid retraction; frequency unknown - cystic macular edema,swelling of the eyes, blurred vision. Cardiac disorders Frequency unknown: bradycardia. Respiratory system disorders: often: rhinitis; infrequently: dyspnea; frequency unknown: bronchospasm (mainly in patients with existing bronchospastic disease), asthma. Skin and subcutaneous tissue disorders: often: eyelid skin pigmentation, hirsutism, periocular skin hyperpigmentation. General disorders and disorders at the injection site: frequency unknown: fatigue. Like other topically applied ophthalmic drugs, TisoptanЃ (bimatoprost + timolol) is absorbed into the systemic circulation. The absorption of timolol can cause undesirable effects similar to those for systemic beta-blocking agents. The number of systemic adverse reactions after topical application is lower than after systemic application.Other adverse reactions that were observed with the use of each of the components of the drug and potentially possible during the period of treatment with TisoptanЃ: Bimatoprost Visual disorders: allergic conjunctivitis, darkening of eyelashes, blepharospasm, retinal hemorrhage, uveitis, periorbital erythema, blurred vision. Heart disorders: increased blood pressure, Raynaud's syndrome, cold extremities. General disorders and disorders at the injection site: asthenia. Gastrointestinal disorders: nausea. Laboratory and instrumental data: changes in the activity of liver enzymes. Timolol Violations of the organ of vision: blepharospasm, retinal hemorrhage, uveitis. Vascular disorders: lowering blood pressure. Respiratory system disordersorgans of the chest and mediastinum: exacerbation of asthma. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Immune system disorders: systemic allergic reactions, including Quincke's edema, urticaria, focal and multiple rashes, rash, anaphylaxis. Metabolic and nutritional disorders: hypoglycemia. Mental disorders: insomnia, depression, nightmares, memory loss. Disturbances from the nervous system: fainting, acute cerebrovascular accident, increased symptoms of myasthenia gravis, paresthesia, cerebral ischemia. Cardiac disorders: atrioventricular block, cardiac arrest, bradycardia, heart failure, congestive heart failure, chest pain,palpitations, swelling. Respiratory, chest and mediastinal disorders: cough. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Respiratory, chest and mediastinal disorders: cough. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Respiratory, chest and mediastinal disorders: cough. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.organs of the chest and mediastinum: cough. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.organs of the chest and mediastinum: cough. Disturbances from the gastrointestinal tract: taste perversion, nausea, diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.diarrhea, dyspepsia, dryness of the oral mucosa, abdominal pain, vomiting. Skin and subcutaneous tissue disorders: alopecia, psoriasis-like rashes or exacerbation of psoriasis, skin rash. Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Musculoskeletal and connective tissue disorders: muscle pain. Genital and breast disorders: sexual dysfunction, decreased libido. General disorders and disorders at the injection site: asthenia / fatigue. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients.
Overdose
With the introduction of the drug TisoptanЃ, an overdose is unlikely or may be associated with toxic effects. Bimatoprost In case of unintentional intake of the drug TisoptanЃ with a preservative inside, the following information may be useful: there were no symptoms of toxic effects of bimatoprost in doses up to 100 ?g / kg / day during a 2-week oral administration in an experiment on rats and mice. The dose used in the study, expressed in mg / m2, exceeds 70 times the possible dose of bimatoprost in case of accidental ingestion of the contents of the vial of TisoptanЃ by a child weighing 10 kg.
Timolol
In case of an overdose of timolol, the following symptoms may occur: bradycardia, decreased blood pressure, bronchospasm, headache, dizziness, shortness of breath, cardiac arrest. Studies have shown that timolol is not completely excreted during hemodialysis. Treatment In case of overdose, symptomatic and supportive therapy is necessary. Interaction with other drugs There have been no special studies to study drug interactions of a fixed combination of bimatoprost + timolol. Potentiation of the effects of the combined use of ophthalmic solutions of beta-blockers and oral blockers of 'slow' calcium channels, guanethidine, beta-blockers, parasympathomimetics, antiarrhythmic drugs (including amiodarone) and cardiac glycosides,which was manifested by a decrease in blood pressure and / or severe bradycardia. It was reported about the potentiation of the systemic effects of beta-blockers (eg, decreased heart rate, depression) with the combined use of timolol with CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine). Periodically reported cases of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline (epinephrine). Patients using TisoptanЃ with other prostaglandin analogs should be monitored to monitor changes in intraocular pressure. Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients with significant corneal damage. Special instructions As well as other ophthalmic medicinal products,TisoptanЃ can enter the systemic circulation. Due to the presence of timolol, a beta-adrenergic component, various types of adverse reactions (from the cardiovascular, respiratory system and other systems) can be observed, as with the use of systemic beta-blockers. The incidence of adverse reactions with local administration of the drug is lower than with systemic use. Cardiovascular system Symptoms of heart failure should be compensated for before using TisoptanЃ. Regular monitoring of the condition of patients with severe heart failure, determination of heart rate is required. Beta-blockers can mask the symptoms of hypoglycemia, hyperthyroidism and cause a worsening of Prinzmetal's angina pectoris, severe peripheral and central vascular disorders,as well as arterial hypotension. Patients with severe peripheral circulatory disorders (for example, severe forms of Raynaud's disease or Raynaud's syndrome) should be used with caution. Respiratory system With the use of timolol, there have been reports of side effects from the respiratory system, including deaths due to bronchospasm in patients with bronchial asthma, and also less often from heart failure. Other beta-blockers Timolol may affect intraocular pressure or enhance the effect of systemic beta-blockers in patients already receiving a systemic beta-blocker. Close monitoring of such patients is recommended. Also, the use of two topical beta-blockers is not recommended.Anaphylactic reactions In patients with atopic manifestations in history and severe anaphylactic reactions to various allergens, doses of epinephrine (adrenaline), which are usually used to relieve anaphylactic reactions, may be ineffective while using beta-blockers. Choroidal Detachment Cases of choroidal detachment have been reported with the use of therapy that reduces the flow of intraocular fluid (eg, timolol, acetazolamide) after filtration surgery. Surgical anesthesia Beta-blocking ophthalmic drugs can suppress the systemic effects of beta-agonists, such as epinephrine. It is necessary to warn the anesthesiologist about the use of timolol by the patient.Liver In patients with mild liver disease or initially increased activity of liver enzymes - alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and / or total bilirubin, bimatoprost had no effect on liver function over a study period of more than 24 months. There are no data on adverse reactions due to the effect of timolol on liver function. Organ of vision Before starting treatment, patients should be informed about the possible growth of eyelashes, increased pigmentation of the eyelid skin and pigmentation of the iris of the eyes, since these side effects were established in the course of studies of bimatoprost and the combination of bimatoprost + timolol. Some changes may be permanent and may be accompanied by the appearance of differences between the eyes if the instillation of the drug was carried out in only one eye.After discontinuation of the drug TisoptanЃ, the pigmentation of the iris may remain constant. After 12 months of treatment with TisoptanЃ, the frequency of iris pigmentation was noted in 0.2% of patients. And after 12 months of treatment with bimatoprost alone in the form of 1.5% eye drops, a further increase in the frequency of this effect was not observed during therapy lasting 3 years. Increased pigmentation in the iris is due to increased production of melanocytes, not just an increase in their number. The duration of the development of the effect of enhancing the pigmentation of the iris is unknown. The iris color change seen with bimatoprost may be subtle over a period of months to years. The use of the drug has no effect on nevi or pigment deposits on the iris. Reportedthat the pigmentation of the periorbital region in some patients is reversible. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases). Skin Hair growth is possible in areas of the skin where the product was accidentally applied. It is important to use TisoptanЃ strictly in accordance with the instructions for medical use and not to allow TisoptanЃ to come into contact with the skin. Excipients The excipient benzalkonium chloride, which is part of TisoptanЃ, can cause irritation of the mucous membrane of the eyes and discoloration of soft contact lenses. Contact lenses must be removed before administration of the drug; they can be put on 15 minutes after instillation. Benzalkonium chloride can cause acute keratitis and / or toxic corneal ulcers.In this regard, it is necessary to monitor the patient's condition with frequent or prolonged treatment with TisoptanЃ in persons with dry eye syndrome and with changes in the cornea. After opening the bottle, it is impossible to exclude the possibility of microbial contamination of its contents, which can lead to inflammatory lesions of the eyes.
The shelf life of the drug after the first opening of the bottle is 28 days. After the specified time has elapsed, the bottle should be discarded, even if the solution has not been completely used. It is recommended to write down the date the bottle was opened on the cardboard box of the medicinal product.
Influence on the ability to drive a car and other mechanisms and
There may be a transient deterioration in vision after administration of the drug, so the patient must wait until vision is fully restored before starting to drive a car or operate machinery.