Ksalakom eye drops, 2.5 ml
Expiration Date: 05/2027
Russian Pharmacy name:
Ксалаком капли глазные, 2.5 мл
Adults (including elderly patients) - 1 drop in the affected eye (s) 1 time / day.
As with the use of any eye drops, in order to reduce the possible systemic effect of the drug, immediately after instillation of each drop, it is recommended to press on the lower lacrimal opening, located at the inner corner of the eye in the lower eyelid, for 2 minutes.
Eye drops in the form of a clear, colorless solution.
1 ml
latanoprost 50 mcg
timolol maleate 6.83 mg,
which corresponds to the content of timolol 5 mg
Excipients: benzalkonium chloride (in the form of a 50% solution) - 200 ?g, sodium hydrogen phosphate anhydrous - 2.89 mg, sodium dihydrogen phosphate monohydrate - 6.39 mg, sodium chloride - 4.1 mg, water d / i - up to 1 ml.
Reactive diseases of the respiratory tract (including bronchial asthma or an indication of its presence in history);
Severe COPD;
sinus bradycardia;
SSSU;
sinoatrial blockade;
AV block II and III degree without artificial pacemaker control;
clinically significant heart failure;
cardiogenic shock;
children and adolescents under 18 years of age (safety and efficacy have not been established);
hypersensitivity to latanoprost, timolol or auxiliary components of the drug.
The drug is used with caution in inflammatory, neovascular, angle-closure glaucoma, open-angle glaucoma in combination with pseudophakia, pigmentary glaucoma (due to the lack of sufficient experience with the drug); aphakia, pseudophakia with rupture of the posterior capsule of the lens; in patients with known risk factors for macular edema (when treating with latanoprost, cases of the development of macular edema, including cystoid edema, have been described); history of herpetic keratitis; AV blockade of the I degree (beta-blockers negatively affect the time of the impulse in the heart muscle); disorders of peripheral circulation (for example, severe forms of Raynaud's syndrome or Raynaud's disease); in patients with corneal diseases, because the drug may cause dryness of the mucous membrane of the eyes.The use of XalacomЃ should be avoided in patients with active herpetic keratitis and recurrent herpetic keratitis, especially associated with the intake of prostaglandin F2? Analogs. Timolol should be used with caution in patients with COPD and only in cases where the potential benefit of the drug for the patient outweighs the risk
pharmachologic effect
Combined antiglaucoma drug, which includes two active components - latanoprost and timolol. The mechanism of lowering elevated IOP in latanoprost and timolol is different, which provides an additional decrease in IOP compared to the effect of using each of these components as monotherapy. Latanoprost - an analogue of prostaglandin F2? - is a selective agonist of FP prostanoid receptors and reduces IOP by increasing the outflow of aqueous humor, mainly by the uveoscleral route, as well as through the trabecular network. Latanoprost has no significant effect on the production of aqueous humor and the permeability of the blood-ophthalmic barrier. During short-term treatment, latanoprost does not cause fluorescein leakage into the posterior segment of the eye in case of pseudophakia.
When used in therapeutic doses, it does not have a significant pharmacological effect on the cardiovascular and respiratory systems. Timolol is a non-selective beta1- and beta2-blocker. It does not have significant internal sympathomimetic activity, does not have a direct depressive effect on the myocardium, does not have membrane stabilizing and local anesthetic activity. Blockade of ?-adrenergic receptors causes a decrease in cardiac output in healthy people and patients with heart disease. In patients with severe myocardial dysfunction, beta-blockers can inhibit the stimulating effect of the sympathetic nervous system, which is necessary for adequate heart function. The blockade of ?-adrenergic receptors in the bronchi and bronchioles leads to an increase in airway resistance under the influence of the parasympathetic nervous system.A similar effect can be dangerous for patients with bronchial asthma and other bronchospastic diseases.
The use of timolol maleate in the form of eye drops causes a decrease in elevated and normal IOP regardless of the presence or absence of glaucoma. Elevated IOP is a major risk factor for glaucomatous visual field loss. The higher the IOP, the higher the likelihood of glaucomatous loss of visual fields and damage to the optic nerve. The exact mechanism of lowering IOP by timolol maleate has not been established.
The results of tonography and fluorometry indicate that the main mechanism of action may be associated with a decrease in the formation of aqueous humor. However, some studies also noted a slight increase in the outflow of aqueous humor. In addition, it is possible to suppress the increased synthesis of cyclic AMP caused by endogenous ?-adrenergic stimulation. There was no evidence of any effect of timolol on the permeability of the blood-ophthalmic barrier. The effect of the drug XalacomЃ occurs within the first hour after application, the maximum effect is observed within 6-8 hours. With repeated use, an adequate decrease in IOP persists for 24 hours after administration.
Pharmacokinetics
The pharmacokinetic interaction between latanoprost and timolol maleate has not been established, although 1-4 hours after using Xalacom, the concentration of latanoprost acid in aqueous humor was approximately 2 times higher than with monotherapy.
Latanoprost
Suction
Latanoprost, being a prodrug, penetrates well through the cornea, while being hydrolyzed to a biologically active form (acid). Cmax in aqueous humor is achieved 2 hours after topical application. The systemic bioavailability of latanoprost acid after topical application of eye drops is 45%. The Vd distribution is 0.16 ± 0.02 L / kg. Latanoprost acid is determined in aqueous humor during the first 4 hours, and in blood plasma - only within the first hour after topical application. Plasma protein binding is 87%.
Metabolism
Latanoprost undergoes hydrolysis in the cornea of ??the eye under the influence of esterases with the formation of biologically active acid. Latanoprost acid, entering the systemic circulation, is metabolized mainly in the liver by beta-oxidation of fatty acids with the formation of 1,2-dinor- and 1,2,3,4-tetranor-metabolites.
Withdrawal
Latanoprost acid is rapidly eliminated from blood plasma. T1 / 2 is 17 minutes. Plasma clearance is 0.4 l / h / kg. Systemic clearance is approximately 7 ml / min / kg. Metabolites are excreted mainly by the kidneys: after topical application, about 88% of the dose is excreted in the urine.
Timolol maleate
Absorption of Cmax of timolol maleate in aqueous humor is achieved after 1 hour. Part of the dose is subjected to systemic absorption and 10-20 minutes after topical application of the drug, 1 drop in each eye 1 time / day (300 ?g / day), Cmax is reached in blood plasma, which is 1 ng / ml.
Metabolism and excretion
Timolol maleate is actively metabolized in the liver. T1 / 2 of timolol maleate from plasma is about 6 hours. Metabolites, as well as a certain amount of unchanged timolol maleate, are excreted by the kidneys.
Side effect
From the side of the organ of vision: very often - increased pigmentation of the iris; often - visual impairment, blepharitis, cataracts, conjunctivitis, conjunctival lesions (follicles, papillary reactions of the conjunctiva, punctate hemorrhages, etc.), corneal lesions (erosion, pigmentation, keratitis, punctate keratitis, etc.), irritation disorders, conjunctiva eyes (including burning sensation and itching in the eyes), eye pain, photophobia, loss of visual fields, increased tear formation. From the endocrine system: often - diabetes mellitus. From the side of metabolism: often - hypercholesterolemia. Mental disorders: often - depression. From the nervous system: often - headache. From the side of the cardiovascular system: often - increased blood pressure. On the part of the skin and subcutaneous tissues: often - hypertrichosis, rash,itching and skin changes (irritation, dermatochalasis, etc.). From the musculoskeletal system: often - arthritis. Infections and invasions: often - sinusitis, upper respiratory tract infections, and other infections. Listed below are other undesirable reactions that were observed during monotherapy with the individual components of the XalacomЃ drug (in addition to those indicated above).
Latanoprost
From the side of the organ of vision: eye irritation (burning sensation, feeling of sand in the eyes, itching, tingling and foreign body sensation); transient point erosion of the corneal epithelium, eyelid edema, keratitis; lengthening, thickening, increasing the number and intensification of eyelash and vellus hair pigmentation; iritis / uveitis; macular edema (in patients with aphakia, in patients with pseudophakia with rupture of the posterior lens capsule, or in patients with risk factors for the development of macular edema), incl. cystoid; a change in the direction of eyelash growth, sometimes causing eye irritation; blurred vision, photophobia, changes in the periorbital region and eyelids, leading to a deepening of the groove of the upper eyelid, periorbital edema, iris cysts. From the side of the cardiovascular system: exacerbation of angina pectoris in patients with coronary artery disease, palpitations.On the part of the skin and subcutaneous tissues: rash, darkening of the eyelid skin and local skin reactions on the eyelids. From the nervous system: dizziness. From the respiratory system: asthma (including acute attacks or exacerbation of the disease in patients with a history of bronchial asthma), shortness of breath. From the musculoskeletal system: muscle pain, joint pain. Infections and invasions: herpetic keratitis. Others: nonspecific chest pain.
Timolol (in the form of eye drops)
Allergic reactions: systemic allergic reactions, incl. anaphylaxis, angioedema, anaphylactic reactions, urticaria, pruritus, localized and generalized rash. From the side of metabolism: hidden symptoms of hypoglycemia in patients with diabetes mellitus. Mental disorders: behavioral changes and mental disorders, incl. confusion, hallucinations, anxiety, disorientation, nervousness, symptoms of depression, memory loss, insomnia, depression, and nightmares. From the nervous system: cerebral ischemia, acute cerebrovascular accident, dizziness, increased symptoms of myasthenia gravis, paresthesia, drowsiness, headache, fainting. From the side of the organ of vision: cystoid macular edema, decreased sensitivity of the cornea; symptoms and signs of eye irritation (eg, burning sensation, itching,feeling of sand in the eyes, increased lacrimation, redness), blepharitis, keratitis, blurred vision, dryness of the mucous membrane of the eyes, corneal erosion, detachment of the choroid after filtration surgery; ptosis, visual impairment, incl. change in refraction and diplopia. On the part of the organ of hearing and vestibular apparatus: tinnitus. From the side of the cardiovascular system: arrhythmia, bradycardia, AV block, chronic heart failure, cardiac arrest, blockade of intracardiac conduction, palpitations, progression of angina pectoris, intermittent claudication, cold hands and feet, lowering blood pressure, Raynaud's syndrome. From the respiratory system: bronchospasm (mainly in patients with previous bronchospastic diseases), cough, shortness of breath, nasal congestion, pulmonary edema and respiratory failure.From the digestive system: diarrhea, dry mouth, impaired taste, dyspepsia, nausea, vomiting, abdominal pain, retroperitoneal fibrosis. On the part of the skin and subcutaneous tissues: alopecia, pseudo-pemphigoid, skin rash, psoriasis-like rash or exacerbation of psoriasis. From the musculoskeletal system: SLE, myalgia. From the reproductive system: decreased libido, impotence, impaired sexual function and Peyronie's disease. Others: anorexia, asthenia / fatigue, chest pain, edema. In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.On the part of the skin and subcutaneous tissues: alopecia, pseudo-pemphigoid, skin rash, psoriasis-like rash or exacerbation of psoriasis. From the musculoskeletal system: SLE, myalgia. From the reproductive system: decreased libido, impotence, impaired sexual function and Peyronie's disease. Others: anorexia, asthenia / fatigue, chest pain, edema. In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.On the part of the skin and subcutaneous tissues: alopecia, pseudo-pemphigoid, skin rash, psoriasis-like rash or exacerbation of psoriasis. From the musculoskeletal system: SLE, myalgia. From the reproductive system: decreased libido, impotence, impaired sexual function and Peyronie's disease. Others: anorexia, asthenia / fatigue, chest pain, edema. In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.chest pain, swelling. In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.chest pain, swelling. In some patients with significant corneal damage, very rare cases of corneal calcification have been reported due to the use of phosphate-containing eye drops.
Application during pregnancy and lactation
Adequate controlled studies of the use of the drug in pregnant women have not been conducted. When conducting epidemiological studies with the use of beta-blockers inside, there were no cases of fetal malformations, however, the risk of intrauterine growth retardation was increased. In addition, symptoms of beta-adrenergic blocking action (such as bradycardia, decreased blood pressure, impaired respiratory function and hypoglycemia) were detected in newborns whose mothers took beta-blockers during pregnancy. If a pregnant woman received beta-blocker therapy, the newborn should be closely monitored in the first days after birth. In this regard, the use of the drug XalacomЃ during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.Latanoprost and its metabolites may be excreted in breast milk; Timolol maleate, when used in the form of eye drops, has also been found in breast milk. Given the risk of developing serious adverse reactions in breastfed newborns, as well as the importance of using the drug for the mother, if it is necessary to use the drug during lactation, the issue of stopping breastfeeding or discontinuing the drug should be decided.if it is necessary to use the drug during lactation, the issue of stopping breastfeeding or discontinuing the drug should be resolved.if it is necessary to use the drug during lactation, the issue of stopping breastfeeding or discontinuing the drug should be resolved.
Application in children
The use of the drug in children and adolescents under 18 years of age is contraindicated (safety and efficacy have not been established).
special instructions
XalacomЃ should be used no more than 1 time / day, since more frequent use leads to a weakening of the effect of lowering IOP. If one dose is missed, the next dose should be administered at the usual time. If the patient is using other eye drops at the same time, they should be applied at intervals of at least 5 minutes. XalacomЃ contains benzalkonium chloride, which can be adsorbed on contact lenses. There are reports of the development of punctate keratopathy and / or toxic ulcerative keratopathy; also with the use of benzalkonium chloride, eye irritation and discoloration of soft contact lenses may occur. It is recommended to carefully monitor the condition of patients who use XalacomЃ often or for a long time, who have dryness of the mucous membrane of the eyes or conditions that damage the cornea.Before instilling drops, contact lenses should be removed and then reinstalled after 15 minutes.
Latanoprost
Latanoprost can cause a gradual increase in the brown pigment content in the iris. As with the use of latanoprost in the form of eye drops, with the use of XalacomЃ, an increase in the pigmentation of the iris was noted in 16-20% of cases among all patients who received the drug for a year (assessment based on photographs). The change in eye color is due to an increase in the number of melanin in the stromal melanocytes of the iris, and not an increase in the number of melanocytes themselves. Typically, brown pigmentation appears around the pupil and spreads concentrically to the periphery of the iris. In this case, the entire iris or parts of it become brown. In most cases, discoloration is minor and may not be clinically apparent. Increased pigmentation of the iris of one or both eyes is observed mainlyin patients with a mixed iris color with a brown base. The drug has no effect on nevi and iris lentigo; pigment accumulation in the trabecular meshwork or the anterior chamber of the eye was not noted. When determining the pigmentation of the iris for more than 5 years, no undesirable consequences of increased pigmentation were revealed even with continued therapy with latanoprost. In patients, the degree of IOP reduction was the same regardless of the degree of iris pigmentation. Therefore, treatment with latanoprost can be continued in cases of increased iris pigmentation, but patients should be monitored regularly and, depending on the clinical situation, treatment may be discontinued. Increased iris pigmentation is usually observed within the first year after starting treatment, rarely after the second or third year.After the fourth year of treatment, this effect was not observed. The rate of progression of pigmentation decreases over time and stabilizes after 5 years. In more distant terms, the effects of increased iris pigmentation have not been studied. After stopping treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible. In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.The rate of progression of pigmentation decreases over time and stabilizes after 5 years. In more distant terms, the effects of increased iris pigmentation have not been studied. After discontinuation of treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible. In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.The rate of progression of pigmentation decreases over time and stabilizes after 5 years. In more distant terms, the effects of increased iris pigmentation have not been studied. After stopping treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible. In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.In more distant terms, the effects of increased iris pigmentation have not been studied. After discontinuation of treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible. In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.In more distant terms, the effects of increased iris pigmentation have not been studied. After discontinuation of treatment, there was no increase in brown pigmentation of the iris, but the change in eye color may be irreversible. In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.In connection with the use of latanoprost, cases of darkening of the eyelid skin have been described, which can be reversible. Latanoprost can cause gradual changes in eyelashes and vellus hair, such as lengthening, thickening, increased pigmentation, increased density and a change in the direction of eyelash growth. Eyelash changes are reversible and disappear after stopping treatment. In patients using drops to treat only one eye, heterochromia may develop.using drops to treat only one eye, the development of heterochromia is possible.using drops to treat only one eye, the development of heterochromia is possible.
Timolol maleate
With local application of beta-blockers, the same undesirable reactions can be observed as with systemic use. Patients with a history of severe heart disease should be constantly monitored for the timely detection of symptoms of heart failure. With local application of timolol maleate, progression of Prinzmetal angina pectoris, peripheral and central circulatory disorders, arterial hypotension, bradycardia, fatal heart failure, severe reactions from the respiratory system (including fatal bronchospasm in patients with bronchial asthma) may occur ... Before undergoing major surgical intervention, the advisability of gradual withdrawal of beta-blockers should be discussed.Drugs in this group interfere with the heart's ability to respond to reflex beta-adrenergic stimulation, which can increase the risk of anesthesia. Cases of prolonged severe arterial hypotension during anesthesia and difficulties in restoring and maintaining cardiac activity have been described. During surgery, the effects of beta-blockers can be eliminated with sufficient doses of adrenergic receptor agonists. Beta-blocking drugs can block the systemic agonistic effects of drugs such as epinephrine. Therefore, it is necessary to warn the anesthesiologist that the patient is receiving timolol. Beta-blockers can enhance the hypoglycemic effect of oral hypoglycemic agents and mask the symptoms of hypoglycemia.They should be used with caution in patients with spontaneous hypoglycemia or diabetes mellitus (especially labile course) receiving insulin or oral hypoglycemic agents. Therapy with beta-blockers can mask the symptoms of hyperthyroidism, abrupt cessation of treatment can exacerbate this disease. When treating with beta-blockers in patients with atopy or severe anaphylactic reactions to various allergens in history, it is possible to increase the response with repeated contact with these allergens. At the same time, epinephrine (adrenaline) in the usual doses used to stop anaphylactic reactions may be ineffective. Rarely, timolol maleate causes increased muscle weakness in patients with myasthenia gravis or myasthenic symptoms (eg, diplopia, ptosis,generalized weakness). With the use of drugs that reduce IOP, detachment of the choroid after filtration procedures - fistulizing operations (trabeculectomy and its modifications, sinusotomy with diathermotrabeculospasis, non-penetrating deep sclerectomy and other fistulizing operations that create new or stimulate existing outflow pathways of intraocular fluid) has been described. Influence on the ability to drive vehicles and work with mechanisms The use of eye drops can cause transient blurred vision. Until this effect disappears, patients should not drive a car or use complex equipment.sinusotomy with diathermotrabeculospasis, non-penetrating deep sclerectomy and other fistulizing operations that create new or stimulate existing pathways for the outflow of intraocular fluid). Influence on the ability to drive vehicles and work with mechanisms The use of eye drops can cause transient blurred vision. Until this effect disappears, patients should not drive a car or use complex equipment.sinusotomy with diathermotrabeculospasis, non-penetrating deep sclerectomy and other fistulizing operations that create new or stimulate existing pathways for the outflow of intraocular fluid). Influence on the ability to drive vehicles and work with mechanisms The use of eye drops can cause transient blurred vision. Until this effect disappears, patients should not drive a car or use complex equipment.patients should not drive a car or use complex equipment.patients should not drive a car or use complex equipment.
Overdose
Latanoprost
Symptoms: in addition to eye irritation and conjunctival hyperemia, other unwanted changes on the part of the organ of vision in case of an overdose of latanoprost are not known. In case of accidental ingestion of latanoprost, it should be borne in mind that 1 bottle with 2.5 ml of solution contains 125 ?g of latanoprost. More than 90% of the drug is metabolized during the 'first pass' through the liver. IV infusion at a dose of 3 ?g / kg in healthy volunteers did not cause any symptoms, however, when administered at a dose of 5.5-10 ?g / kg, nausea, abdominal pain, dizziness, fatigue, hot flashes and sweating were observed. These symptoms resolve within 4 hours after stopping the infusion. In patients with moderate bronchial asthma, administration of latanoprost at a dose 7 times higher than the therapeutic dose did not cause bronchospasm.
Timolol maleate
—имптомы: описаны случаи непреднамеренной передозировки глазных капель тимолола малеата, в результате чего наблюдались эффекты, сходные с таковыми при системном применении бета-адреноблокаторов: головокружение, головна¤ боль, одышка, брадикарди¤, бронхоспазм, остановка сердца. ¬ исследовании in vitro было показано, что при диализе тимолола малеат легко выводитс¤ из плазмы или цельной крови. ” пациентов с почечной недостаточностью тимолола малеат диализировалс¤ хуже.
Ћечение: при передозировке салакома провод¤т симптоматическую терапию.
Ћекарственное взаимодействие
¬заимодействие препарата салакомЃ с другими препаратами специально не изучалось. Ќе рекомендуетс¤ одновременное с салакомом применение внутрь других бета-адреноблокаторов, поскольку возможно выраженное снижение ¬v? или усиление системных эффектов бета-адреноблокаторов. ѕри одновременном закапывании в глаза двух аналогов простагландинов описано парадоксальное повышение ¬v?, поэтому одновременное применение двух и более простагландинов, их аналогов или производных не рекомендуетс¤. ѕри одновременном применении тимолола малеата с эпинефрином (адреналином) иногда развивалс¤ мидриаз. ¬озможно аддитивное действие с развитием системной артериальной гипотензии и/или выраженной брадикардии при сочетании тимолола малеата со следующими препаратами: блокаторы медленных кальциевых каналов, средства, вызывающие снижение уровн¤ катехоламинов, бета-адреноблокаторы, антаритмические средства, сердечные гликозиды, гуанетидин. —ообщалось об усилении действи¤ системных бета-адреноблокаторов (например, снижение „——, депресси¤) при одновременном применении ингибиторов изофермента CYP2D6 (например, хинидина, флуоксетина, пароксетина) и тимолола. Ѕета-адреноблокаторы могут усиливать гипогликемическое действие противодиабетических средств. ѕри внезапной отмене клонидина отмечаетс¤ повышение ј?. ?анна¤ реакци¤ может усиливатьс¤ при одновременном применении с бета-адреноблокаторами.
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