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Active ingredients
Bisoprolol
Release form
Pills
Composition
Bisoprolol fumarate 2.5 mg. Excipients: lactose monohydrate - 68.15 mg, microcrystalline cellulose - 16 mg, magnesium stearate - 0.35 mg, crospovidone - 3 mg.
Pharmacological effect
Bisoprolol is a selective 1-blocker without its own sympathomimetic activity, it does not have a membrane stabilizing effect. Bisoprolol has only a slight affinity for the 2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for the 2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol does not generally affect airway resistance and metabolic processes in which 2-adrenoreceptors are involved. The selective effect of the drug on 1-adrenoreceptors is maintained outside the therapeutic range. With a single use in patients with coronary artery disease with no signs of CHF, bisoprolol reduces heart rate, stroke volume of the heart and, as a result, reduces the ejection fraction and the need for myocardium in oxygen. With long-term therapy initially increased OPS decreases.
Pharmacokinetics
Bisoprolol absorption is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to insignificant metabolism during the "first pass" through the liver (about 10%) is about 90% after ingestion. Food intake does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its plasma concentration is proportional to the dose taken in the dose range from 5 to 20 mg. Cmax in plasma is reached 2-3 hours after ingestion. Distribution Bisoprolol is distributed quite widely. Vd is 3.5 l / kg. Communication with proteins of a blood plasma reaches about 30%. Metabolism Bisoprolol is metabolized by 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 small role. Clearance Bisoprolol clearance is determined by the balance between kidney excretion in unchanged form (about 50%) and liver metabolism (about 50%) to metabolites, which are then also eliminated by the kidneys. Total clearance is 15 l / h. T1 / 2 is 10-12 hours.There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous impaired liver or kidney function.
Indications
- chronic heart failure.
Contraindications
- acute heart failure, chronic heart failure in the decompensation stage, requiring inotropic therapy; - cardiogenic shock; - AV block II and III degree in patients without pacemaker; - sick sinus syndrome; - sinoatrial block; - severe bradycardia (heart rate less than 60 beats / min); - severe arterial hypotension (systolic blood pressure less than 100 mm Hg); - severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD); - pronounced disorders of the peripheral arterial circulation or Raynaud's syndrome; - pheochromocytoma (without the simultaneous use of alpha-blockers); - metabolic acidosis; - age up to 18 years (no clinical experience in children); - lactose intolerance, lactase deficiency or glucose-galactose malabsorption; - hypersensitivity to bisoprolol or to any of the excipients. With caution Desensitization therapy, Prinzmetal angina pectoris, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, grade I AV-blockade, severe renal failure (CC less than 20 ml / min), marked impaired liver function, psoriasis , restrictive cardiomyopathy, congenital heart defects or valvular heart disease with severe hemodynamic disorders, CHF with myocardial infarction during the last 3 months, strict diet.
Use during pregnancy and lactation
Pregnancy Use of the drug Bidop Cor in pregnancy is possible only when the intended benefit of therapy for the mother outweighs the potential risk of side effects in the fetus and / or child. 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, and the growth and development of the unborn child should be monitored, and in the event of adverse events with respect to pregnancy and / or the fetus, alternative therapeutic measures should be taken. You should carefully examine the newborn after childbirth.In the first three days of life, symptoms of bradycardia and hypoglycemia may occur. Breastfeeding Period It is not known whether bisoprolol passes into breast milk. Therefore, taking the drug Bidop Cor is not recommended for women during lactation. If necessary, use of the drug, breastfeeding should be discontinued.
Dosage and administration
Bidopor Kor should be taken orally once a day with a small amount of liquid in the morning before breakfast, during or after it. Tablets should not be chewed or powdered. The standard treatment regimen for CHF includes the use of ACE inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), β-blockers, diuretics, and, optionally, cardiac glycosides. Starting treatment of chronic heart failure with Bidop Cor requires the mandatory conduct of a special phase of titration and regular medical monitoring. A prerequisite for treatment with Bidop Cor is stable CHF with no signs of exacerbation. Treatment of CHF with Bidop Cor begins in accordance with the following titration scheme. In this case, individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e. the dose can be increased only if the previous dose was well tolerated. The recommended initial dose is 1.25 mg (0.5 tab. 2.5 mg) 1 time / day. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg (1.5 pills. 2.5 mg), 5 mg, 7.5 mg (3 pills. 2.5 mg or 1.5 pills. Bisoprolol, 5 mg with risk) and 10 mg (2 tab. Bisoprolol 5 mg or 1 tab. Bisoprolol 10 mg) 1 time / day. To ensure the above dosing regimen, Bidop may be used. Each subsequent increase in dose should be carried out no less than 2 weeks. If an increase in the dose is poorly tolerated by the patient, a dose reduction is possible. The maximum recommended dose for CHF is 10 mg of the drug BidopKor 1 time / day. During titration, regular monitoring of blood pressure, heart rate and degree of CHF symptoms is recommended. The aggravation of the symptoms of CHF is possible from the first day of using the drug. If the patient does not tolerate the maximum recommended dose of the drug, a gradual dose reduction is possible.During the titration phase or after it, a temporary worsening in the course of CHF, hypotension or bradycardia may occur. In this case, it is recommended first of all to carry out the correction of doses of drugs associated therapy. It may also require a temporary reduction in the dose of Bidopor Cor or its withdrawal. After the patient's condition has stabilized, the dose should be re-titrated or continued treatment. Duration of treatment Treatment with Bidop Cor is usually a long-term therapy. Impaired renal or hepatic function If there is a mild or moderately impaired liver or kidney function, dose adjustment is usually not required. With pronounced 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 such patients should be carried out with extreme caution. Elderly patients Dose adjustment is not required. Children It is not recommended to prescribe Bidop Cor to children under 18, due to the fact that there is no experience of clinical use of the drug in children. To date, there is insufficient data on the use of bisoprolol in patients with CHF in combination with type 1 diabetes, severe impaired renal function and / or liver, restrictive cardiomyopathy, congenital heart disease, or valvular heart disease with severe hemodynamic disorders. Also, until now there has not been obtained sufficient data on patients with chronic heart failure with myocardial infarction in the last 3 months.
Side effects
The frequency of adverse reactions is determined as follows: 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). The nervous system: 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. On the part of the organ of hearing and labyrinth disorders: rarely - hearing impairment. From the side of the heart and blood vessels: very often - bradycardia; often - aggravation of symptoms of CHF, a feeling of cooling or numbness in the extremities, a pronounced decrease in blood pressure; infrequently - a violation of AV-conduction, orthostatic hypotension.On the part of the respiratory system, organs of the chest and mediastinum: infrequently - bronchospasm in patients with bronchial asthma or an obstruction of the respiratory tract in history; rarely - allergic rhinitis. On the part of the gastrointestinal tract: often - nausea, vomiting, diarrhea, constipation; rarely - hepatitis. From the musculoskeletal and connective tissue: infrequently - muscular weakness, muscle cramps. On the part of the skin and subcutaneous tissues: rarely - hypersensitivity reactions, such as pruritus, rash, hyperemia of the skin; very rarely - alopecia. Beta-blockers may exacerbate the symptoms of psoriasis or cause a psoriasis-like rash. On the part of the genital organs and the mammary gland: rarely - violations of potency. General disorders and disorders at the injection site: often - asthenia, fatigue. Impact on the results of laboratory and instrumental studies: rarely - hypertriglyceridemia, increased activity of hepatic transaminases (ALT, ACT). If any of the side effects indicated in the instructions are aggravated, or the patient has noticed any other side effects not indicated in the instructions, you should inform your doctor.
Overdose
Symptoms The most common symptoms of overdose are: AV blockade, severe bradycardia, marked reduction in blood pressure, bronchospasm, acute heart failure and hypoglycemia. The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with CHF are highly sensitive. Treatment In case of overdose, first of all, it is necessary to stop taking the drug and begin supportive symptomatic therapy. In severe bradycardia: in / in the introduction of atropine. If the effect is insufficient, with caution you can enter the drug, which has a positive chronotropic effect. Sometimes you may need a temporary setting of an artificial pacemaker. With a pronounced decrease in blood pressure: in / in the introduction of plasma-substituting solutions and vasopressor drugs. With AV block: patients should be monitored and treated with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.When exacerbation of CHF: in / in the introduction of diuretics, drugs with a positive inotropic effect and vasodilators. In case of bronchospasm: use of bronchodilators, incl. beta2-adrenomimetics and / or aminophylline. In hypoglycemia: in / in the introduction of dextrose (glucose).
Interaction with other drugs
Simultaneous use of other drugs may affect the efficacy and tolerability of bisoprolol. This interaction can also occur in cases where 2 drugs are taken over a short period of time. The doctor must be informed about the admission of other drugs, even if they are taken without a doctor's prescription (ie, over-the-counter drugs). Non-recommended combinations Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) while used with bisoprolol may reduce AV conductivity and myocardial contractility. Blockers of "slow" calcium channels (BMCC), such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impairment of AV conduction. In particular, in / in the introduction of verapamil to patients taking beta-blockers, can lead to severe arterial hypotension and AV-blockade. Central antihypertensive drugs (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilatation due to a decrease in central sympathetic tone. Abrupt cancellation, especially before the abolition of beta-blockers, may increase the risk of ricochet hypertension. Combinations that require extra caution BMIC, dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine), while used with bisoprolol, may increase the risk of arterial hypotension. In patients with CHF, the risk of a subsequent deterioration of the contractile function of the heart cannot be excluded. Class III antiarrhythmic drugs (eg, amiodarone) may exacerbate the disturbance of AV conduction. The action of beta-blockers for local use (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lower blood pressure, decrease in heart rate). Parasympathomimetics with simultaneous use with bisoprolol may increase the violation of AV-conductivity and increase the risk of developing 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. Funds for general anesthesia may increase the risk of a cardiodepressive effect, leading to arterial hypotension. Cardiac glycosides when applied 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 antihypertensive effect of bisoprolol. The simultaneous use of Bidopor with beta-adrenomimetic drugs (for example, isoprenaline, dobutamine) can reduce the effect of both drugs. The combination of bisoprolol with adrenomimetics that affect α- and α-adrenergic receptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these drugs that occur with α-adrenoreceptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers. Antihypertensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the antihypertensive effect of bisoprolol. Mefloquine when used concomitantly with bisoprolol may increase the risk of developing bradycardia. MAO inhibitors (with the exception of MAO-B inhibitors) can enhance the antihypertensive effect of beta-blockers. Simultaneous use can also lead to the development of hypertensive crisis. Rifampicin: a slight decrease in T1 / 2 of bisoprolol is possible due to the induction of rifampicin by the hepatic isoenzymes of cytochrome P450. Usually, dose adjustment is not required. Ergotamine derivatives: possible exacerbation of peripheral circulatory disorders.
special instructions
You should not abruptly interrupt 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.At the initial stages of treatment with Bidop Cor, patients need constant monitoring. The drug should be used with caution in the following cases: - diabetes mellitus with significant fluctuations in glucose concentration in the blood: symptoms of a pronounced decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations or excessive sweating, may be masked; - strict diet; - conducting desensitization therapy; - AV block I degree; - Prinzmetal angina; - disturbances of the peripheral arterial blood circulation of mild and moderate degree (at the beginning of therapy, symptoms may increase); - psoriasis (including in the anamnesis). Respiratory system: in case of bronchial asthma or COPD, simultaneous use of bronchodilating agents is indicated. In patients with bronchial asthma, an increase in airway resistance is possible, which requires a higher dose of beta2-adrenomimetics. Allergic reactions: beta-blockers, including the drug Bidop Cor, can increase the sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the action of beta-blockers. Epinephrine (adrenaline) therapy does not always give the expected therapeutic effect. General anesthesia: when conducting general anesthesia, the risk of blockade of beta-adrenoreceptors should be considered. If it is necessary to stop treatment with Bidop Cor before surgery, this should be done gradually and completed 48 hours before general anesthesia. The anesthesiologist should be warned that the patient is taking Bidop Cor. Pheochromocytoma: in patients with adrenal tumors (pheochromocytoma), Bidop Cor can only be prescribed with the use of alpha-blockers. Hyperthyroidism: in the treatment with Bidop Cor, the symptoms of hyperthyroidism (hyperthyroidism) may be masked. The effect on the ability to drive vehicles and 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 and mechanisms may be impaired.This should be paid special attention to at the beginning of treatment, after changing the dose, and also while drinking alcohol.