Concor pills p/o 10mg №30×1

Composition 1 film-coated tablet, 5 mg contains: Core: Active substance: bisoprolol fumarate – 5 mg. Excipients: calcium hydrogen phosphate, anhydrous – 132.0 mg; corn starch, fine powder – 14.5 mg; colloidal silicon dioxide, anhydrous – 1.5 mg; microcrystalline cellulose – 10.0 mg; crospovidone – 5.5 mg; magnesium stearate – 1.5 mg. Film shell: Hypromellose 2910/15 – 2.20 mg, macrogol 400 – 0.53 mg, dimethicone 100 – 0.11 mg, iron dye yellow oxide (E 172) – 0.02 mg, titanium dioxide (E 171) – 0.97 mg. 1 film-coated tablet, 10 mg contains: Core: Active substance: bisoprolol fumarate -10 mg. Excipients: calcium hydrogen phosphate, anhydrous – 127.5 mg; corn starch, fine powder – 14.0 mg; colloidal silicon dioxide, anhydrous – 1.5 mg; microcrystalline cellulose – 10.0 mg; crospovidone – 5.5 mg; magnesium stearate – 1.5 mg. Film shell: Hypromellose 2910/15 – 2.200 mg, macrogol 400 – 0.530 mg, dimethicone 100 – 0.220 mg, iron dye yellow oxide (E 172) – 0.120 mg, iron dye red oxide (E 172) – 0.002 mg, titanium dioxide ( E 171) – 0.850 mg. DescriptionFilm-coated tablets 5 mg: Light yellow, heart-shaped, biconvex film-coated tablets, scored on both sides. Film-coated tablets 10 mg: Light orange, heart-shaped, biconvex film-coated tablets, scored on both sides. Pharmacotherapeutic group Selective beta-blockers. ATX code: C07AB07. Pharmacological properties Pharmacodynamics Mechanism of action Bisoprolol is a highly selective beta1-blocker without its own sympathomimetic and significant membrane stabilizing activity. It has only a slight affinity for the beta-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for the beta2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol in general does not affect airway resistance and metabolic processes in which beta2-adrenergic receptors are involved. Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol 1 time per day, its therapeutic effect persists for 24 hours due to the 10-12-hour half-life from blood plasma. As a rule, the maximum reduction in blood pressure (BP) is achieved 2 weeks after the start of treatment. With a single use in patients with coronary heart disease (CHD), bisoprolol reduces heart rate and stroke volume of the heart and, as a result, reduces cardiac output and oxygen consumption. With long-term administration, initially increased total peripheral vascular resistance decreases. A decrease in plasma renin activity is considered as one of the mechanisms of the antihypertensive action of beta-blockers. Bisoprolol reduces the activity of the sympathoadrenal system (SAS) by blocking the beta1-adrenergic receptors of the heart. This leads to a slowdown in the contraction of the heart and a decrease in contractility, and, as a result, to a decrease in oxygen consumption. The reduction in oxygen consumption is a desirable effect of therapy in patients with angina pectoris as a manifestation of CAD. Pharmacokinetics Absorption Bisoprolol is almost completely absorbed, and its bioavailability after oral administration is about 90%. The “first pass” effect is ≤ 10%. This results in an absolute bioavailability of about 90%. Distribution Communication with plasma proteins is about 30%. The volume of distribution is 3.5 l/kg. Metabolism and excretion Bisoprolol is excreted from the body in two equally effective ways: 50% is metabolized in the liver to form inactive metabolites, which are then excreted by the kidneys, and the remaining 50% is excreted in the urine unchanged. Since excretion through the kidneys and liver occurs to the same extent, dosage adjustment for patients with impaired liver function or mild or moderate renal insufficiency is usually not required (see section Dosage and Administration). The total clearance of bisoprolol is 15 l/h. The plasma half-life is 10-12 hours (see Pharmacodynamics section). Linearity The kinetics of bisoprolol is linear and does not depend on age. Indications for use arterial hypertension ischemic heart disease: stable angina pectoris chronic heart failure Contraindications Bisoprolol is contraindicated in patients with: acute heart failure or episodes of decompensated heart failure requiring intravenous inotropic therapy. cardiogenic shock; atrioventricular block II-III degree (without a pacemaker); sick sinus syndrome; sinoatrial blockade; symptomatic bradycardia; symptomatic arterial hypotension; severe bronchial asthma; severe form of obliterating diseases of peripheral arteries or severe form of Raynaud’s syndrome; untreated pheochromocytoma (see Precautions section); metabolic acidosis; hypersensitivity to bisoprolol or other components of the drug (see Composition section). Method of application and dosage Arterial hypertension and stable angina pectoris Doses Treatment with bisoprolol should be started with low doses and then gradually increase the daily dose. In all cases, the regimen and dose is selected by the doctor for each patient individually, in particular, taking into account the heart rate and the patient’s condition. Arterial hypertension The recommended dose is 5 mg of bisoprolol fumarate once a day. With mild arterial hypertension (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg may be sufficient to adequately control the disease. If necessary, the dose can be increased to 10 mg once a day. Further increase in dose is possible only in exceptional cases. The maximum recommended dose is 20 mg once daily. Ischemic heart disease (stable angina) The recommended dose is 5 mg of bisoprolol fumarate once a day. If necessary, the dose can be increased to 10 mg once a day. Further increase in dose is possible only in exceptional cases. The maximum recommended dose is 20 mg once daily. Chronic heart failure The standard treatment regimen for chronic heart failure (CHF) includes the use of an ACE inhibitor (or angiotensin II receptor antagonists in case of intolerance to ACE inhibitors), a beta-blocker, diuretics, and, when necessary, cardiac glycosides. At the beginning of treatment with bisoprolol, patients should be in a stable condition (without acute insufficiency). It is recommended that the attending physician has experience in the treatment of CHF. During the titration phase or after it, a temporary worsening of the course of heart failure, arterial hypotension or bradycardia may occur. Doses Treatment of CHF with bisoprolol requires a mandatory titration phase. Treatment with bisoprolol should begin with a gradual increase in dose according to the steps below: 1.25 mg once a day for 1 week, if well tolerated, increase to 2.5 mg once a day over the next week, if well tolerated, increase up to 3.75 mg once daily for the next week, if well tolerated increase to 5 mg once daily for the next 4 weeks, if well tolerated increase to 7.5 mg once daily for the next 4 weeks weeks, if well tolerated, increase to 10 mg once daily as maintenance therapy. The maximum recommended dose is 10 mg once daily. During the titration phase, close monitoring of vital signs (heart rate, blood pressure) and symptoms of progression of heart failure is necessary. Symptoms may appear as early as the first day after the start of therapy. Adjustment of treatment In case of poor tolerance of the maximum recommended dose, a gradual dose reduction should be considered. In the event of a temporary worsening of the course of heart failure, arterial hypotension or bradycardia, it is recommended to reconsider the dosage of concomitant therapy drugs. You may also need to temporarily reduce the dose of bisoprolol or cancel it. After stabilization of the patient’s condition, the possibility of re-administration and / or titration of the dose of bisoprolol with its increase should always be considered. When deciding to stop taking, a gradual dose reduction is recommended, since abrupt withdrawal can lead to an acute impairment of the patient’s condition. Treatment of CHF with bisoprolol is usually long-term. Patients with impaired hepatic or renal function In patients with impaired hepatic or renal function of mild or moderate degree, dose adjustment is usually not required in the treatment of arterial hypertension and coronary artery disease. With severe renal dysfunction (creatinine clearance less than 20 ml / min.) And in patients with severe liver disease, the maximum daily dose should not exceed 10 mg. Experience with the use of bisoprolol in dialysis patients is limited. There are no data indicating the need to change the dosing regimen. Information regarding the pharmacokinetics of bisoprolol in patients with CHF with concomitant impaired liver or kidney function is not available. In this regard, increasing the dose in these groups of patients should be carried out with additional precautions. Elderly patients Dose adjustment is not required in elderly patients. Children Due to the lack of experience with the use of bisoprolol in children, its administration to patients under 18 years of age is not recommended. Method of application Bisoprolol tablets should be taken once a day in the morning. May be taken with food. Tablets should be swallowed with a small amount of liquid, without chewing. Duration of treatment for all indications for use The duration of treatment is not limited and depends on the cause and severity of the disease. Treatment with bisoprolol should not be interrupted suddenly, especially in patients with coronary artery disease, as abrupt withdrawal can lead to an acute impairment of the patient’s condition. If it is necessary to stop treatment, the daily dose should be reduced gradually (for example, halving at weekly intervals). Application during pregnancy and lactation Pregnancy The pharmacological effects of bisoprolol may have a harmful effect on pregnancy and / or the fetus / newborn. In general, beta-adrenergic blockers reduce placental blood flow, which can lead to growth retardation, fetal death, abortion, or preterm birth. Adverse reactions (eg, hypoglycemia and bradycardia) may occur in the fetus and newborn. If treatment with a beta-blocker is necessary, it is desirable that it be a selective beta1-blocker. Bisoprolol should not be used during pregnancy unless there is a clear clinical need for it. If treatment with bisoprolol is regarded as necessary, uteroplacental blood flow should be monitored, as well as the growth and development of the fetus should be monitored. In the event of adverse effects on pregnancy and/or the fetus, alternative treatments should be considered. The newborn should be carefully examined after delivery. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur. Breast-feeding There are no data on the excretion of bisoprolol into breast milk. Therefore, taking bisoprolol is not recommended for women during breastfeeding. Side effects The frequency of adverse reactions listed below was determined according to the following: often ≥ 1/100, < 1/10; infrequently ≥ 1/1000, < 1/100; rarely ≥ 1/10,000, < 1/1000; very rarely < 1/10,000; frequency unknown (cannot be determined based on available data). Laboratory and instrumental data Rarely: an increase in the concentration of triglycerides and the activity of hepatic transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)). Cardiac disorders Uncommon: bradycardia, AV conduction disorder; exacerbation of pre-existing symptoms of heart failure. Nervous system disorders Common: dizziness*, headache*. Rare: syncope. On the part of the organ of vision Rare: decreased lacrimation (should be taken into account when wearing contact lenses). Very rare: conjunctivitis. On the part of the organ of hearing and the labyrinth Rarely: hearing impairment. Respiratory, thoracic and mediastinal disorders Uncommon: Bronchospasm in patients with asthma or a history of airway obstruction. Rare: allergic rhinitis. Gastrointestinal disorders Common: Gastrointestinal complaints such as nausea, vomiting, diarrhea, constipation. Skin and subcutaneous tissue disorders Rare: hypersensitivity reactions such as pruritus, rash, flushing of the skin. Very rare: alopecia. Beta-blockers may precipitate or exacerbate psoriasis or cause a psoriasis-like rash. Muscular, skeletal and connective tissue disorders Uncommon: muscle weakness, muscle cramps. Vascular disorders Common: Feeling cold or numb in the extremities. Uncommon: hypotension. General disorders Common: asthenia (in patients with CHF), fatigue*. Uncommon: asthenia (in patients with arterial hypertension or angina pectoris). Liver and biliary tract disorders Rare: hepatitis. Reproductive system and mammary gland disorders Rare: potency disorders. Psychiatric disorders Uncommon: depression, sleep disturbances. Rarely: nightmares, hallucinations. * Especially often these symptoms appear at the beginning of the course of treatment. Usually these phenomena are mild and disappear, as a rule, within 1-2 weeks after the start of treatment. It is important to report suspected adverse reactions after registration of the medicinal product in order to ensure continuous monitoring of the benefit-risk ratio of the medicinal product. If an adverse reaction occurs that is indicated in this package leaflet or not mentioned in it, patients are advised to contact their doctor. Healthcare professionals are encouraged to report any suspected adverse drug reactions to the Republican Unitary Enterprise "Center for Expertise and Testing in Healthcare" (see section Information about the manufacturer). OverdoseSymptoms The most common symptoms of an overdose of bisoprolol are bradycardia, arterial hypotension, bronchospasm, acute heart failure and hypoglycemia. To date, several cases of overdose (maximum: 2000 mg) of bisoprolol have been reported in patients with arterial hypertension and / or coronary artery disease with the development of bradycardia and / or hypotension; all patients recovered. Sensitivity to a single high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with heart failure may be very sensitive. Treatment In case of overdose, it is necessary to stop treatment with bisoprolol and carry out supportive and symptomatic therapy. Limited data suggest that bisoprolol is difficult to dialyze. Based on the expected pharmacological activity and recommendations for other beta-blockers, the following general measures should be considered clinically reasonable. With bradycardia: intravenous atropine. If the effect is insufficient, isoprenaline or an agent with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be required. In hypotension: intravenous administration of plasma-substituting solutions and vasopressor drugs, intravenous administration of glucagon can also have a positive effect. With atrioventricular block II and III degree: patients should be under constant supervision, infusion of isoprenaline should be prescribed. If necessary, the setting of an artificial pacemaker. With an exacerbation of the course of CHF: intravenous administration of diuretics, inotropic drugs, as well as vasodilators. For bronchospasm: administer bronchodilators such as isoprenaline, beta-agonists and/or aminophylline. With hypoglycemia: intravenous administration of glucose. Interaction with other drugs Contraindicated combinations Calcium antagonists such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can have a negative effect on myocardial contractility and atrioventricular conduction. Intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and atrioventricular blockade. Centrally acting antihypertensive agents (such as clonidine, methyldopa, moxonidine, rilmenidine) may lead to worsening of heart failure due to a decrease in central sympathetic tone (decrease in heart rate and cardiac output, vasodilation). Abrupt withdrawal, especially before the withdrawal of beta-blockers, may increase the risk of developing "rebound" arterial hypertension. Combinations requiring caution Class I antiarrhythmic drugs (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can potentiate the effect on atrioventricular conduction and increase the negative inotropic effect. Dihydropyridine calcium antagonists (for example, felodipine and amlodipine), when used simultaneously with bisoprolol, may increase the risk of arterial hypotension, and an increased risk of further impairment of heart pumping function in patients with existing CHF cannot be excluded. Class III antiarrhythmics (eg, amiodarone) may potentiate the effect on atrioventricular conduction. Parasympathomimetics, when used simultaneously with bisoprolol, can increase the time of atrioventricular conduction and the risk of developing bradycardia. Topical beta-blockers (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol. With the simultaneous use of insulin and oral antidiabetic agents, the hypoglycemic effect increases. Blockade of beta-adrenergic receptors can hide the symptoms of hypoglycemia. The concomitant use of bisoprolol and general anesthetics may cause a decrease in reflex tachycardia and increase the risk of hypotension (see Precautions for more information). Simultaneous administration of cardiac glycosides with bisoprolol can lead to a decrease in heart rate, an increase in atrioventricular conduction time. Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect of bisoprolol. The combination of beta-sympathomimetics (eg, isoprenaline, dobutamine) with bisoprolol may reduce the effect of both drugs. The combination of bisoprolol with sympathomimetics that affect beta- and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) can contribute to the manifestation of vasoconstrictive effects mediated by alpha-adrenergic receptors, leading to an increase in blood pressure and exacerbation of intermittent claudication. Such interactions are more likely with the use of non-selective beta-blockers. The simultaneous use of bisoprolol with antihypertensive agents, as well as with other agents with a possible hypotensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension. Combinations requiring clarification Mefloquine, when used simultaneously with bisoprolol, may increase the risk of developing bradycardia. Monoamine oxidase (MAO) inhibitors (with the exception of MAO-B inhibitors) may increase the hypotensive effect of beta-blockers, but may also increase the risk of developing a hypertensive crisis. PrecautionsTreatment with bisoprolol should not be interrupted suddenly, especially in patients with coronary artery disease, as this may lead to a temporary deterioration in the condition of the heart (see section Dosage and Administration). The drug should be used with caution in the following cases: diabetes mellitus with significant fluctuations in blood glucose concentration: symptoms of hypoglycemia (such as tachycardia, palpitations or excessive sweating) may be masked; strict post; conducting desensitizing therapy. As with other beta-blockers, bisoprolol can increase both sensitivity to allergens and the severity of anaphylactic reactions. Therapy with epinephrine does not always lead to the expected therapeutic effect; atrioventricular block I degree; Prinzmetal's angina; obliterating diseases of peripheral arteries. Exacerbation of symptoms may occur, especially at the beginning of therapy. There is no experience with the use of bisoprolol in patients with CHF in combination with the following diseases and conditions: insulin-dependent diabetes mellitus (type I); severe renal dysfunction; severe liver dysfunction; restrictive cardiomyopathy; congenital heart defects; hemodynamically significant organic lesion of the heart valves; myocardial infarction within the last 3 months. Although cardioselective (beta-1) beta-blockers may have a lesser effect on lung function than non-selective beta-blockers, their use, like any other beta-blockers, should be avoided in patients with obstructive airway disease, unless there is a clear clinical need for it. When such grounds exist, bisoprolol may be used with caution. In patients with obstructive airway disease, treatment with bisoprolol should be started at the lowest possible dose, and patients should be carefully monitored for new symptoms (eg, shortness of breath, exercise intolerance, cough). In bronchial asthma or other chronic obstructive pulmonary diseases that can cause such symptoms, the simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be a periodic increase in airway resistance, which may require a higher dose of beta-adrenergic agonists. General anesthesia: In patients under anesthesia, the use of beta-blockers reduces the incidence of arrhythmia and myocardial ischemia during induction and intubation, as well as in the postoperative period. The current recommendation is to continue maintenance beta blockade in the perioperative period. The anesthesiologist should be aware of beta-blockade due to potential interactions with other drugs that can lead to bradyarrhythmias, decreased reflex tachycardia, and decreased reflex ability to compensate for blood loss. If it is deemed necessary to discontinue beta-blocker therapy prior to surgery, this should be done gradually and completed approximately 48 hours prior to general anesthesia. The combination of bisoprolol with calcium antagonists such as verapamil or diltiazem, with class I antiarrhythmic drugs and with centrally acting antihypertensive agents is usually not recommended (for more information, see section Interaction with other drugs). Patients with psoriasis (including a history) should use beta-blockers (eg, bisoprolol) after a careful assessment of the benefit/risk ratio. In patients with pheochromocytoma, bisoprolol can be prescribed only after blockade of alpha receptors has been ensured. Symptoms of thyrotoxicosis may be masked while taking bisoprolol. The use of the drug Concor® may cause positive results during doping control. Influence on the ability to drive vehicles and complex mechanisms Bisoprolol does not affect the ability to drive vehicles according to the results of a study in patients with coronary artery disease. However, due to individual reactions, the ability to drive vehicles or work with machines and mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also with the simultaneous use of alcohol. Release form: 10 tablets in a blister of aluminum foil and PVC; 3 or 5 blisters, together with instructions for use, are placed in a cardboard box. 30 tablets in a blister of aluminum foil and PVC; 1 blister with instructions for use is placed in a cardboard box. 25 tablets in a blister of aluminum foil and PVC; 2 blisters together with instructions for use are placed in a cardboard box. Storage conditionsStore at a temperature not exceeding 30°C. Keep out of the reach of children. Shelf life 5 years. Do not use after the expiration date. Terms of dispensing from pharmacies By prescription. Manufacturer / holder of the registration certificate Merck KGaA, Germany (Merck KGaA, Germany) Frankfurter Strasse, 250, 64293, Darmstadt, Germany (Frankfurter Strasse 250, 64293 Darmstadt, Germany). /o 10mg No. 30x1Instruction for use for Concor tablets p/o 10mg No. 30x1