Concor Cor tablets p/o 2.5mg №30×1

Name:
Concor Cor tabl p / film.ob. 2.5 mg in bl. in pack. No. 30×1 Main active ingredient Bisoprolol
Description:
White, heart-shaped, biconvex film-coated tablets, scored on both sides. Dosage 2.5 mg Pharmacological action 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 generally does not affect airway resistance and metabolic processes in which beta2-adrenergic receptors are involved. The selective effect of the drug on beta1-adrenergic receptors persists beyond the therapeutic dose range. Clinical efficacy and safety A total of 2647 patients were included in the CIBIS II study. 83% (n = 2202) were NYHA class III and 17% (n = 445) were NYHA class IV. Patients had a diagnosis of stable symptomatic systolic heart failure (ejection fraction ? 35% based on echocardiography). Overall mortality was reduced from 17.3% to 11.8% (34% relative reduction). There was a reduction in the incidence of sudden death (3.6% vs. 6.3%, 44% relative reduction) and a reduction in the number of episodes of heart failure requiring hospitalization (12% vs. 17.6%, 36% relative reduction). In addition, there was a significant improvement in the functional state in accordance with the NYHA classification. At the beginning of the course of treatment and during titration of bisoprolol, there were cases of hospitalization due to bradycardia (0.53%), arterial hypotension (0.23%) and acute decompensation (4.97%), but they were not more frequent than in the placebo group. (0%, 0.3% and 6.74%). The number of fatal and disabling strokes during the entire study period was 20 in the bisoprolol group and 15 in the placebo group. The CIBIS III study included 1010 patients aged ? 65 years old with mild to moderate chronic heart failure (CHF; NYHA class II or III) and left ventricular ejection fraction ? 35% who have not previously taken an angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, or angiotensin receptor blocker. Patients were treated with a combination of bisoprolol and enalapril for a period of 6 to 24 months after an initial 6-month therapy with either bisoprolol or enalapril. When using bisoprolol as the initial 6-month treatment, there was a trend towards a higher frequency of worsening CHF. The non-inferiority of initial treatment with bisoprolol compared with enalapril has not been proven, although the analysis of the data obtained according to the protocol did not demonstrate the advantage of initial monotherapy with bisoprolol, although both strategies for initiating CHF treatment showed a similar primary combined end point, namely death and hospitalization in the end of the study (32.4% in the bisoprolol group versus 33.1% in the enalapril group in the population that completed the study protocol). The study shows that bisoprolol can also be used in elderly patients with mild to moderate CHF. Bisoprolol is also used to treat hypertension and angina pectoris. With a single use in patients with coronary heart disease (CHD) without signs of CHF, 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. Pharmacokinetics Absorption Bisoprolol is almost completely absorbed, and its bioavailability after oral administration is about 90%. Distribution The volume of distribution is 3.5 l/kg. Communication with blood plasma proteins is about 30%. Metabolism and excretion Bisoprolol is excreted from the body in two ways. 50% is metabolized in the liver to form inactive metabolites, which are then excreted by the kidneys. The remaining 50% is excreted in the urine unchanged. The total clearance of bisoprolol is 15 l/h. The plasma half-life of 10-12 hours provides a 24-hour effect when dosing once a day. Linearity The kinetics of bisoprolol is linear and does not depend on age. Special Populations Since elimination via the kidneys and liver occurs to the same extent, dosage adjustment for patients with impaired liver function or renal insufficiency is not required. Pharmacokinetics in patients with stable CHF and with impaired liver or kidney function has not been studied. In patients with CHF (NYHA stage III), plasma levels of bisoprolol are higher and the half-life is longer compared to healthy volunteers. The maximum plasma concentration at steady state is 64 ± 21 ng / ml at a daily dose of 10 mg and the elimination half-life is 17 ± 5 hours. Indications for use Treatment of stable chronic heart failure (CHF) with reduced left ventricular systolic function in addition to ACE inhibitors and diuretics, as well as cardiac glycosides (if necessary) Use during pregnancy and lactation Pregnancy The pharmacological effects of bisoprolol may have a harmful effect on pregnancy and /or 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. Precautions The treatment of stable CHF with bisoprolol requires a special titration phase. Treatment with bisoprolol should not be interrupted suddenly (unless there are clear indications for this), especially in patients with coronary artery disease, as this may lead to a temporary deterioration in the condition of the heart. At the initial stages of treatment with bisoprolol and when it is canceled, patients need constant monitoring. 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. The drug should be used with caution in the following cases: bronchospasm (bronchial asthma, obstructive airway disease); diabetes mellitus with significant fluctuations in blood glucose concentration; symptoms of hypoglycemia 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; general anesthesia. In patients under anesthesia, the use of beta-blockers reduces the number of cases 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). 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, Concor Cor can 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 beta2-adrenergic agonists. 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 Cor may cause positive results during doping control. The use of the drug Concor Cor as a doping agent may be harmful to health. Interaction with other drugs Not recommended 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. Class I antiarrhythmic drugs (for example, quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone), when used simultaneously with bisoprolol, can potentiate the effect on atrioventricular conduction and enhance the negative inotropic effect. 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 Dihydropyridine calcium antagonists (eg, felodipine and amlodipine), when used concomitantly with bisoprolol, may increase the risk of arterial hypotension, and an increased risk of further impairment of cardiac pumping function in patients with existing CHF cannot be excluded. Class III antiarrhythmics (eg, amiodarone) may potentiate the effect on atrioventricular conduction. Topical beta-blockers (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol. Parasympathomimetics, when used simultaneously with bisoprolol, can increase the time of atrioventricular conduction and the risk of developing bradycardia. 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) may contribute to the manifestation of vasoconstrictive effects mediated by alpha-adrenergic receptors, leading to an increase in blood pressure and aggravation 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. Bisoprolol is contraindicated in patients with CHF with: acute heart failure or episodes of decompensated heart failure requiring intravenous inotropic therapy; cardiogenic shock; atrioventricular block II-III degree; sick sinus syndrome; sinoatrial blockade; symptomatic bradycardia; symptomatic arterial hypotension; severe bronchial asthma; severe obliterating peripheral arterial disease or severe Raynaud’s syndrome; untreated pheochromocytoma (see section Precautions); metabolic acidosis; hypersensitivity to bisoprolol or other components of the drug. Composition One film-coated tablet contains: Core: Active substance: bisoprolol fumarate – 2.5 mg. Excipients: calcium hydrogen phosphate, anhydrous; corn starch; silicon dioxide colloidal, anhydrous; cellulose microcrystalline; crospovidone; magnesium stearate. Film shell: hypromellose 2910/15, macrogol 400, dimethicone 100, titanium dioxide (E 171). Route of administration and doses The standard regimen for the treatment of 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: Titration phase 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. Treatment adjustment: In case of poor tolerance of the maximum recommended dose, 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 liver or kidney function: There is no information on the pharmacokinetics of bisoprolol in patients with CHF with concomitant impaired liver or kidney function. 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. 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. How to use: 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. Overdose Symptoms In case of overdose (for example, a daily dose of 15 mg instead of 7.5 mg), third-degree atrioventricular block, bradycardia and dizziness have been reported. In general, the most common symptoms of bisoprolol overdose 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. In this regard, it is imperative to start the treatment of these patients with a gradual increase in dose according to the scheme given in the Dosage and Administration section. 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: the appointment of bronchodilators, such as isoprenaline, beta2-agonists and / or aminophylline. With hypoglycemia: intravenous administration of glucose. Side effects The frequency of adverse reactions listed below was determined as follows: very often? 1/10; often ? 1/100, < 1/10; infrequently ? 1/1000, < 1/100; rarely ? 1/10,000, < 1/1000; very rare < 1/10,000, frequency unknown (cannot be estimated from the available data) Cardiac disorders: Very common: bradycardia Common: exacerbation of symptoms of heart failure Uncommon: atrioventricular conduction disturbance Laboratory and instrumental findings: Rare: increased triglycerides and activity of "liver" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)). Nervous system disorders: Often: dizziness, headache. Rarely: loss of consciousness. 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 exacerbate psoriasis symptoms or cause a psoriasis-like rash. Muscular, skeletal and connective tissue disorders: Uncommon: muscle weakness, muscle cramps. Vascular disorders: Often: feeling cold or numbness in the extremities, arterial hypotension. Uncommon: orthostatic hypotension. General disorders: Often: asthenia, fatigue. Liver and biliary tract disorders: Rare: hepatitis. Reproductive system and mammary gland disorders: Rare: potency disorders. Mental disorders: Infrequently: sleep disturbances, depression. Rarely: nightmares, hallucinations. 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). Storage conditions At a temperature not higher than 25 °C. Keep out of the reach of children. Buy Concor Cor tablets p / o 2.5 mg No. 30x1