Bisoprolol (in the form of fumarate) 2.5 mg adjuvants: colloidal silicon dioxide (aerosil) - 1.5 mg, potato starch - 18 mg, lactose monohydrate (milk sugar) - 54 mg, povidone - 3 mg, microcrystalline cellulose - 20 mg, magnesium stearate - 1 mg of film coating composition: aq-02140 selekoat - 3 mg (hypromellose (hydroxypropylmethylcellulose) - 1.8 mg, macrogol (polyethylene glycol 400) - 0.33 mg, macrogol (polyethylene glycol 6000) - 0.45 mg, titanium dioxide - 0.39 mg, dye sun-setting yellow - 0.03 mg).
Selective beta1-blocker. Does not possess its own sympathomimetic activity and membrane stabilizing properties. It has only a slight affinity for β2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for β2-adrenergic receptors involved in the regulation of metabolism. Consequently, bisoprolol does not generally affect the airway resistance and metabolic processes in which β2-adrenoreceptors are involved. Bisoprolol reduces the activity of the sympathoadrenal system by blocking the heart β1-adrenoreceptors. When taken once for oral administration in patients with IHD without signs of chronic heart failure (CHF) bisoprolol decreases heart rate, decreases stroke volume and, as a result, decreases ejection fraction and myocardial oxygen demand. With long-term therapy initially increased OPS decreases. Reduction of renin activity in the blood plasma is considered as one of the components of the hypotensive action of beta-blockers. As a rule, the maximum decrease in blood pressure is achieved 2 weeks after the start of therapy.
Absorption of bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Slightly exposed to the first passage through the liver (approximately 10%), as a result of which bioavailability after oral administration is approximately 90%. Food intake does not affect bioavailability. Cmax in the blood plasma is achieved in 2-3 hours. The distribution of bisoprolol is distributed quite widely. Vd is 3.5 l / kg. Binding to plasma proteins reaches approximately 30%. Bisoprolol demonstrates linear kinetics, and its plasma concentration is proportional to the dose taken in the range from 5 to 20 mg. Metabolism Metabolizes along the oxidative pathway without subsequent conjugation. All metabolites are polar (water soluble) and excreted by the kidneys.The major metabolites found in plasma and urine do not exhibit pharmacological activity. The data obtained as a result of experiments with human liver microsomes in vitro, show that bisoprolol is metabolized primarily using the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role. about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. Total clearance is 15 l / h. T1 / 2 - 10-12 hours. Pharmacokinetics in special clinical situations. There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous dysfunction of the liver or kidneys.
- chronic heart failure (CHF); - arterial hypertension; - IHD: prevention of attacks of stable angina pectoris.
- cardiogenic shock; - collapse; - acute heart failure; - chronic heart failure in the decompensation stage, requiring inotropic therapy; - AV II and III degree AV blockade (without pacemaker); - sinoatrial blockade; - SSS; - arterial hypotension (systolic BP less than 90 mm Hg); - pronounced disorders of the peripheral circulation or Raynaud's syndrome; - severe bronchial asthma; - severe COPD; - pheochromocytoma (without simultaneous use of alpha-adrenergic blockers); - metabolic acid h; - simultaneous use of MAO inhibitors (except for MAO type B inhibitors); - lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome; - lactation period; - age up to 18 years (efficacy and safety not established) - hypersensitivity to components drug and other beta-blockers. With caution, you should use the drug during desensitization therapy; Printsmetal angina pectoris; hyperthyroidism; type 1 diabetes and diabetes mellitus with significant fluctuations in glucose concentration in the blood; AV blockade I degree; severe renal failure (CC less than 20 ml / min); severe impaired liver function; psoriasis; restrictive cardiomyopathy; congenital heart defects or valvular heart disease with severe hemodynamic disorders; chronic heart failure with myocardial infarction in the last 3 months; pheochromocytoma (with concomitant use of alpha-blockers); following a strict diet.
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
In pregnancy, the drug Aritel Cor should be recommended for use only if the benefit to the mother exceeds the risk of side effects in the fetus. As a rule, beta-blockers reduce blood flow in the placenta and can affect the development of the fetus. The blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child should be observed. In case of occurrence of adverse events in relation to pregnancy and / or the fetus, alternative therapies should be applied. It is necessary to carefully examine the newborn after childbirth. In the first 3 days of life, symptoms of hypoglycemia and bradycardia may occur. There is no data on the release of bisoprolol in breast milk. Therefore, the use of the drug Aritel Cor is not recommended for women during lactation. If necessary, the use of the drug during lactation breastfeeding should be discontinued.
Dosage and administration
The drug is taken orally 1 time / day, in the morning, regardless of the meal. Tablets must be taken with a small amount of liquid; Tablets should not be chewed or powdered. Chronic heart failure (CHF). Starting treatment of chronic heart failure with Aritel Cor requires a special phase of titration and regular medical monitoring. A prerequisite for treatment with Aritel Cor is stable chronic heart failure without signs of exacerbation. Treatment of CHF with Aritel Corstarts according to the following titration scheme. The recommended initial dose is 1.25 mg (1/2 tab. 2.5 mg) 1 time / day. It is necessary to monitor the individual adaptation of the patient to the prescribed dose. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg 1 time / day. Each subsequent dose increase should be carried out no less than 2 weeks later. If an increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible. The maximum recommended dose in the treatment of CHF is 10 mg 1 time / day. If the patient does not tolerate the maximum recommended dose of the drug, a gradual reduction in dose is possible. Regular monitoring of blood pressure, heart rate and the severity of CHF symptoms is recommended during the titration. The worsening of the symptoms of CHF is possible already from the first day of the drug use. During the phase of titration or after it, a temporary worsening of the course of CHF, hypotension or bradycardia may occur. In this case, it is recommended, first of all, to adjust the doses of drugs associated with concomitant therapy. It may also require a temporary reduction in the dose of Aritel Cor or withdrawal of the drug. After stabilization of the patient's condition, re-titration should be carried out, or treatment should continue. Arterial hypertension and stable angina In all cases, the doctor selects each patient’s dosing regimen individually, in particular, taking into account the patient’s heart rate and patient condition. If necessary, the dose can be increased up to 10 mg 1 time / day. The maximum recommended dose is 20 mg 1 time / day. The duration of treatment for all indications. Treatment with Aritel Cor is usually carried out for a long time. required. In severe impaired renal function (CC less than 20 ml / min) and in patients with severe liver diseases, the maximum daily dose is 10 mg. Increasing the dose in these patients should be carried out with extreme caution. Elderly patients do not need dose adjustment. There are currently insufficient data on the use of bisoprolol in patients with CHF combined with type 1 diabetes, severe impaired renal function and / or liver, restrictive cardiomyopathy, congenital heart defects or valvular heart disease with severe hemodynamic disorders.
The frequency of the side reactions given below was determined according to the following: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000, including individual reports). On the CNS side: often - dizziness *, headache *; rarely - loss of consciousness. Mental disorders: infrequently - depression, insomnia; rarely - hallucinations, nightmares. On the part of the organ of vision: rarely - reduction of tearing (should be considered when wearing contact lenses); very rarely - conjunctivitis. From the side of the organ of hearing: rarely - hearing impairment. From the side of the cardiovascular system: very often - bradycardia (in patients with CHF); often - aggravation of the symptoms of CHF (in patients with CHF), a feeling of cooling and numbness in the extremities, a pronounced decrease in blood pressure, especially in patients with CHF; infrequently - a violation of AV conduction, bradycardia (in patients with arterial hypertension or angina), worsening symptoms of CHF (in patients with arterial hypertension or angina), orthostatic hypotension. respiratory tract history; rarely - allergic rhinitis. From the digestive system: often - nausea, vomiting, diarrhea, constipation; rarely - hepatitis. From the musculoskeletal system: infrequently - muscular weakness, muscle cramps. From the skin: rarely - hypersensitivity reactions such as pruritus, rash, skin hyperemia; very rarely - alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash. On the reproductive system: rarely - impaired potency. Laboratory tests: rarely - an increase in triglyceride concentration and activity of hepatic transaminases in the blood (ACT, ALT). Others: often - asthenia (in patients with CHF), fatigue *; infrequently, asthenia (in patients with arterial hypertension or angina pectoris). * In patients with arterial hypertension or angina pectoris, these symptoms usually appear at the beginning of the course of treatment, are mild and disappear within 1-2 weeks after the start of treatment.
Symptoms: AV blockade, bradycardia, decreased blood pressure, bronchospasm,acute heart failure and hypoglycemia. Treatment: in the event of an overdose, first of all it is necessary to stop taking the drug and start symptomatic supportive therapy. With severe bradycardia, i.v. with atropine. If the effect is insufficient, with caution, you can enter a tool with a positive chronotropic effect. Sometimes it may be necessary to temporarily install an artificial pacemaker. If blood pressure is too low, IV injection of plasma-substituting solutions and vazopressor administration are required. During an AV blockade, patients should be constantly monitored and treated with alpha and beta adrenomimetics, such as epinephrine. If necessary, staging an artificial pacemaker. In acute exacerbation of CHF, i.v. administration of diuretics, drugs with a positive inotropic effect, and vasodilators. In case of bronchospasm, use of bronchodilators, incl. beta2-sympathomimetic and / or aminophylline. For hypoglycemia - in / in the introduction of dextrose (glucose).
Interaction with other drugs
Non-recommended combinations When treating chronic heart failure, class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) can also decrease AV conductivity and contractility of the heart while treating chronic heart failure. angina blockers of slow calcium channels (BCCA) of the verapamil type and, to a lesser extent, diltiazem, with simultaneous use with bisoprolol Oguta lead to a decrease of myocardial contractility and AV-conduction disturbance. In particular, i.v. administration of verapamil to patients taking beta-blockers may result in severe arterial hypotension and AV blockade. Central-acting anti-potent drugs (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and a decrease in cardiac output , as well as vasodilation due to a decrease in central sympathetic tone. Abrupt cancellation, especially before the abolition of beta-blockers may increase the risk of ricochet hypertension. Combinationsrequiring special care When treating arterial hypertension, stable angina pectoris, class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) can also decrease AV conductivity and myocardial contractility when used with bisoprolol. Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) when used concomitantly with bisoprolol can reduce AV conductivity and myocardial contractility. , nifedipine, felodipine, amlodipine) with simultaneous use with bisoprolol may increase the risk of arterial hypotension. In patients with chronic heart failure, the risk of subsequent deterioration of the contractile function of the heart cannot be ruled out. Class III antiarrhythmic drugs (eg, amiodarone) may exacerbate AV-conduction disturbances. Beta-adrenergic blockers for topical use (eg, eye drops for the treatment of glaucoma) may increase systemic effects of bisoprolol (lowering blood pressure, reducing heart rate). Parasimpathomimetics when used simultaneously with bisoprolol may increase the disturbance of AV conduction and increase the risk of developing I bradycardia. The hypoglycemic effect of insulin or hypoglycemic agents for oral administration may increase. Symptoms of hypoglycemia (in particular, tachycardia) may be masked or suppressed. Such interactions are more likely when using non-selective beta-blockers. General anesthesia agents may increase the risk of a cardiodepressant effect, leading to arterial hypotension. Cardiac glycosides when used simultaneously with bisoprolol can lead to an increase in the duration of the impulse, and thus to the development of bradycardia. NSAIDs can reduce the hypotensive effect of bisoprolol. Simultaneous use of the drug with beta-adrenergic mimics (for example, isoprenaline, dobutamine) can The combination of bisoprolol with adrenomimetics that affect the α- and β-adrenergic receptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these agents that occur with the participation of α-adrenoreceptors, leading to an increase in blood pressure.Such interactions are more likely when using non-selective beta-blockers. Anti-hypertensives, as well as other means with a possible hypotensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can increase the hypotensive effect of bisoprolol. bradycardia. MAO inhibitors (with the exception of MAO inhibitors of type B) can enhance the hypotensive effect of beta-blockers. Simultaneous use can also lead to the development of hypertensive crisis.
You should not abruptly interrupt drug treatment and change the recommended dose without first consulting a doctor, because This can lead to a temporary deterioration in the activity of the heart. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dose should be reduced gradually. Control of the condition of patients taking bisoprolol should include monitoring of heart rate and blood pressure (at the beginning of treatment - daily, then every 3-4 months), ECG, blood glucose concentration in patients with sugar diabetes (1 time in 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months). Patients should be trained in how to calculate the heart rate and instruct on the need for medical consultation with a heart rate less than 50 beats / min. Before starting treatment, it is recommended to conduct a study of the function of external respiration in patients with burdened bronchopulmonary history. Approximately in 20% of patients with angina, beta-adrenergic blockers are not effective. The main reasons are severe coronary atherosclerosis with a low ischemic threshold (HR less than 100 beats / min) and an increased end diastolic volume of the left ventricle that disrupts subendocardial blood flow. In smoking patients, the effectiveness of beta-adrenergic blockers is lower. Patients using contact lenses should take into account that against the background of treatment, a reduction in the production of tear fluid is possible. When using the drug in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless chickpea effective alpha adrenoblockade) .If hyperthyroidism preparation can mask certain clinical signs of hyperthyroidism (hyperthyroidism), such as tachycardia.Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated, as this may increase the symptoms. In diabetes mellitus, the use of the drug may mask the tachycardia caused by hypoglycemia. In contrast to non-selective beta-adrenergic blockers, insulin-induced hypoglycemia practically does not increase and does not delay the restoration of blood glucose to normal values. When used simultaneously with clonidine, the latter can be stopped only a few days after discontinuation of the drug Aritel Cor. sensitivity and lack of effect of the usual doses of epinephrine (adrenaline) on the background of burdened allergological anamnesis. If necessary, Conducting a planned surgical treatment, the drug is discontinued 48 hours prior to general anesthesia. If the patient took the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effect. The patient should be warned by the anesthesiologist that he is taking the drug Aritel Cor. The reciprocal activation of the vagus nerve can be eliminated by intravenous atropine (1-2 mg). Drugs that reduce catecholamine stores (including reserpine) can enhance the effect of beta-blockers, therefore, patients taking such combinations of drugs should be under constant medical supervision to detect arterial hypotension or bradycardia. Patients with bronchospastic diseases can be prescribed cardioselective adrenoblockers in case of intolerance and / or ineffectiveness of other antihypertensive drugs, but the dose should be strictly followed. Overdose is dangerous for the development of bronchospasm. In case of increasing bradycardia (less than 50 bpm) in patients, arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe impaired liver function and kidney it is necessary to reduce the dose or discontinue treatment. It is recommended to stop therapy in case of the development of depression caused by taking beta-blockers. It is impossible to abruptly interrupt the treatment because of the risk of severe arrhythmias and myocardial infarction.Cancellation is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days). It is necessary to cancel the drug before examining the content in the blood and urine of catecholamines, normetanephrine and vanillin-almond acid; antinuclear antibody titers. Effect on the ability to drive vehicles and control mechanisms. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.