More info
Active ingredients
Bisoprolol
Release form
Pills
Composition
Bisoprolol hemifumarate 10 mg; Auxiliary substances: microcrystalline cellulose - 40 mg, calcium hydrophosphate - 103.6 mg, corn starch - 10 mg, croscarmellose sodium - 3.4 mg, magnesium stearate - 1.5 mg, silicon dioxide, colloidal anhydrous - 1.5 mg. Shell composition: lactose monohydrate - 2.48 mg, hypromellose - 1.92 mg, titanium dioxide - 1.8 mg, macrogol 4000 - 0.68 mg, iron (III) dye yellow oxide - 0.12 mg, iron (III) dye red oxide - 0.002 mg.
Pharmacological effect
Bisoprolol is a selective beta1-adrenoblocker, without its own sympathomimetic activity, does not have a membrane stabilizing effect. As with other beta1-blockers, the mechanism of action in hypertension is unclear. However, it is known that bisoprolol reduces renin activity in the blood plasma, reduces myocardial oxygen demand, and reduces heart rate. It has hypotensive, antiarrhythmic and antianginal effects. By blocking the β1-adrenoreceptors of the heart in low doses, it reduces catecholamine-stimulated formation of cAMP from ATP, reduces the intracellular current of calcium ions, inhibits all heart functions, reduces AV-conductivity and excitability. If the therapeutic dose is exceeded, it has a beta2-adrenergic blocking effect. OPSS at the beginning of the drug, in the first 24 hours, increases (as a result of the reciprocal increase in β-adrenoreceptor activity and the elimination of stimulation of β2-adrenoreceptors), which returns to its original value after 1-3 days, and decreases with prolonged use. with a decrease in the minute volume of blood, sympathetic stimulation of peripheral vessels, a decrease in the activity of the sympathoadrenal system (is more important for patients with initial renin hypersecretion), recovery of feelings telnosti in response to a decrease in blood pressure and the influence of the central nervous system. In hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months; the anti-anginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in contractility and other myocardial functions, diastole lengthening, and improvement in myocardial perfusion.By increasing the end-diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles, oxygen demand may increase, especially in patients with chronic heart failure. When used in moderate therapeutic doses, in contrast to non-selective beta-blockers, organs containing β2-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of the peripheral arteries, bronchi and uterus) and carbohydrate metabolism. Does not cause the delay of sodium ions in the body; the severity of atherogenic action does not differ from that of propranolol.
Pharmacokinetics
Absorption; Bisoprolol is almost completely absorbed from the gastrointestinal tract, food intake does not affect absorption. Bioavailability is about 90%. Tmax in plasma - 2-4 hours after ingestion.; Distribution and metabolism; Binding to plasma proteins - 26-33%. Metabolized in the liver, the metabolites of bisoprolol do not possess pharmacological activity. Permeability through the BBB and placental barrier is low, in small quantities excreted in breast milk.; Elimination; T1 / 2 is 9-12 hours, which makes it possible to use the drug 1 time / day. Excreted by the kidneys (50% unchanged), less than 2% through the intestines.
Indications
- arterial hypertension; - IHD: prevention of attacks of stable angina pectoris; - chronic heart failure (as part of combination therapy).
Contraindications
- acute heart failure and chronic heart failure in the stage of decompensation, requiring inotropic therapy; - cardiogenic shock; - collapse; - AV block II and III degree (without pacemaker); - sinoatrial block; - sick sinus syndrome; - bradycardia (heart rate less than 50 beats / min before treatment); - severe hypotension (systolic blood pressure less than 100 mm Hg. Art.); - Cardiomegaly (without signs of heart failure); - severe forms of bronchial asthma and COPD in history; - pronounced disorders of the peripheral circulation; - Raynaud's syndrome; - metabolic acidosis; - pheochromocytoma (without the simultaneous use of alpha-blockers); - concomitant use of floctafenin and sultopride; - lactose intolerance, lactase deficiency,glucose-galactose malabsorption; - age up to 18 years (efficacy and safety have not been established); - hypersensitivity to bisoprolol or to any of the components of the drug and to other beta-blockers. With caution: - bronchospasm (bronchial asthma, obstructive respiratory diseases); - conducting desensitization therapy; - hyperthyroidism; - diabetes mellitus type 1 and diabetes mellitus with significant fluctuations in the concentration of glucose in the blood; - severe renal failure (CC less than 20 ml / min); - severe abnormal liver function; - psoriasis; - impaired peripheral blood circulation (at the beginning of therapy, symptoms may increase); - general anesthesia; - myasthenia gravis; - AV block I degree; - Prinzmetal angina; - restrictive cardiomyopathy; - congenital heart defects or valvular heart disease with severe hemodynamic disorders; - chronic heart failure with myocardial infarction in the last 3 months; - depression (including in the anamnesis); - pheochromocytoma (simultaneous use of alpha-blockers); - strict diet; - Allergic reactions in history.
Use during pregnancy and lactation
Bisoprolol does not have a direct cytotoxic, mutagenic and teratogenic effect, but it has pharmacological effects that may have a harmful effect on the course of pregnancy and / or on the fetus or the newborn. Usually, beta-blockers reduce placental perfusion, leading to slower fetal growth, fetal death, miscarriages, or premature birth. A fetus and a newborn child may experience pathological reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.; Byol drug; should not be used during pregnancy, use is possible if the benefit to the mother exceeds the risk of side effects in the fetus and / or child. In the case when the drug treatment Byol; considered necessary, the bloodstream in the placenta and the uterus should be monitored, as well as the growth and development of the unborn child should be monitored, and in case of adverse events in relation to pregnancy and / or the fetus, alternative methods of therapy should be adopted. You should carefully examine the newborn after childbirth.Symptoms of hypoglycemia and bradycardia usually occur during the first 3 days of life. There is no data on the penetration of bisoprolol into breast milk. Therefore, the use of the drug Byol; not recommended for women during lactation. If necessary, the use of the drug during lactation, breastfeeding should be stopped.
Dosage and administration
Byol drug; take orally, in the morning on an empty stomach, 1 time / day, with a small amount of liquid, in the morning before breakfast, during or after it. Tablets should not be chewed or rubbed into powder. In all cases, the doctor will select the dose and dose for each patient individually, in particular, taking into account the heart rate and the patient's condition; Hypertension and IHD; In hypertension and IHD, Byol; apply 5 mg 1 time / day. If necessary, the dose is increased to 10 mg 1 time / day; In the treatment of hypertension and angina, the maximum daily dose is 20 mg 1 time / day; Chronic heart failure (CHF); Start of CHF treatment with Byol; requires a special phase of titration and regular medical supervision.; Prerequisite for treatment with Byol; is stable CHF with no signs of exacerbation.; Treatment of CHF with Byol; starts according to the following titration scheme. This may require individual adaptation 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. To ensure an appropriate titration process, it is recommended to use the drug in smaller doses at the initial stages of treatment. The recommended initial dose is 1.25 mg (1/4 tab. 5 mg) 1 time. per day Depending on the individual tolerance, the dose should be gradually increased to 2.5 mg (1/2 tab. 5 mg), 3.75 mg (3/4 tab. 5 mg.), 5 mg (1 tab. 5 mg or 1/2 tab. 10 mg), 7.5 mg (3/4 tab. 10 mg) and 10 mg 1 time / day with an interval of at least 2 weeks or more. If an increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible. The maximum daily dose in the treatment of CHF is 10 mg 1 time / day. Regular monitoring of blood pressure, heart rate and symptoms of increasing CHF severity is recommended during the titration.The worsening of CHF symptoms is possible already from the first day of using the drug. 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 pay attention to the selection of the dose of concomitant standard therapy. A temporary reduction in the dose of Byol may also be required; 5 mg or cancellation of treatment.; Once the patient’s condition has stabilized, the dose should be re-titrated, or continued treatment. Impaired renal or hepatic function; Impaired mild or moderate hepatic or renal function usually does not require dose adjustment. 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.; To date, not enough data on the use of the drug Byol; 5 mg in patients with CHF associated with type 1 diabetes, severe impaired renal function and / or liver, restrictive cardiomyopathy, congenital heart defects, or hemodynamically-induced heart disease. 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 the adverse reactions listed below was determined accordingly to the following (WHO classification): very often (≥10%); often (≥1%, but <10%); infrequently (≥0.1%, but <1%); rarely (≥0.01%, but <0.1%); very rarely (<0.01%, including individual reports); From the side of the cardiovascular system: very often - a decrease in heart rate (bradycardia, especially in patients with CHF), a heartbeat; often - marked reduction in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased disturbance of peripheral circulation, feeling cold in the extremities (paresthesia); rarely - impaired AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, worsening of CHF with the development of peripheral edema (swelling of the ankles, feet; shortness of breath), chest pain. From the nervous system: often - dizziness, headache, asthenia, fatigue, sleep disorders, depre disorder; rarely - confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremor, muscle cramps.Typically, these phenomena are mild and usually take place within 1-2 weeks after the start of treatment. From the sense organs: rarely - impaired vision, decreased tearing (should be considered when wearing contact lenses), tinnitus, decreased hearing loss, earache; very rarely - dry and sore eyes, conjunctivitis, taste disorders. On the part of the respiratory system: rarely - bronchospasm in patients with bronchial asthma or obstructive diseases of the respiratory tract; rarely, allergic rhinitis; nasal congestion. On the part of the digestive system: often - nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, abdominal pain; rarely - hepatitis, increased activity of liver enzymes (ALT, AST), increased concentration of bilirubin, change in taste.; From the musculoskeletal system: rarely - arthralgia, back pain.; From the genitourinary system: very rarely - a violation of potency, weakening Libido. From the laboratory parameters: rarely - an increase in the concentration of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, leukopenia.; Allergic reactions: rarely - pruritus, rash, urticaria; On the part of the skin: rarely - increased sweating, skin flushing, exanthema, psoriasis-like skin reactions; very rarely - alopecia, beta-blockers can exacerbate the course of psoriasis.; Other: withdrawal syndrome (increased angina pectoris attacks, increased blood pressure).
Overdose
Symptoms: arrhythmia, ventricular premature beats, severe bradycardia, AV blockade, marked reduction in blood pressure, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions; , should be taken adsorbing means, to conduct symptomatic therapy. With severe bradycardia - in / in the introduction of atropine. If the effect is insufficient, with caution, you can enter a tool with 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 vazopressorov. When hypoglycemia can be shown in / in the introduction of glucagon or in / in the introduction of dextrose (glucose).With AV blockade: patients must be under constant surveillance, and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker. With exacerbation of CHF - in / in the introduction of diuretics, drugs with a positive inotropic effect, as well as vasodilators. With bronchospasm - the appointment of bronchodilators, incl. beta2-adrenomimetics and / or aminophylline.
Interaction with other drugs
The effectiveness and tolerance of bisoprolol may be affected by the simultaneous use of other medicines. This interaction can also occur in cases where two medicines are taken over a short period of time. The patient needs to inform the doctor about taking other medicines, even if they are taken without a doctor's prescription (ie, non-prescription drugs); Not recommended combinations; Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flekainid, propafenone ) with simultaneous use with bisoprolol, may decrease AV conductivity and myocardial contractility.; Slow calcium channel blockers (BMCC), such as verapamil and, to a lesser extent, diltiazem while being applied and bisoprolol can 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 hypotension and AV blockade. Central anti-hypertensive drugs (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to decompensation of CHF due to reduction of heart rate and reduction of cardiac output, as well as the appearance of symptoms of vasodilation due to a decrease in central sympathetic tone.; Combinations requiring special care; BCCA dihydropyridine derivatives (for example, nifedipine, felodion in, amlodipine), while the use of bisoprolol may increase the risk of 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 (for example,amiodarone) may exacerbate the disturbance of AV conduction.; The effect of beta-blockers for topical use (for example, eye drops for treating glaucoma) may enhance the systemic effects of bisoprolol: pronounced decrease in blood pressure, decrease in heart rate.; Parasympathomimetics with simultaneous use with bisoprolol may enhance AV impairment -conductivity and increase the risk of bradycardia.; Simultaneous use of bisoprolol with beta-adrenomimetics (eg, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.; C Mixing bisoprolol with adrenomimetics that affect the β- and β-adrenoreceptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these agents that occur with the participation of β-adrenoreceptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers. Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol. Iodine-containing radiopaque contrast agents for intravenous injection the risk of anaphylactic reactions.; Phenytoin with a / in the introduction, means for inhalation anesthesia (derivatives of hydrocarbons) increase; severity cardiodepressive effect and the likelihood of reducing blood pressure.; The effectiveness of insulin and hypoglycemic agents for oral administration may vary with treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure) .; Lidocaine and xanthines clearance (except for theophylline) may decrease due to their possible increase concentration; in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.; The antihypertensive effect weakens NSAIDs (sodium ion retention and blockade of the synthesis of staglandins by the kidneys), GCS and estrogens (sodium ion retention); Cardiac glycosides increase the risk of developing or worsening bradycardia, AV blockade, cardiac arrest, and heart failure.; Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease AD.; The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins during bisoprolol treatment may be prolonged.; Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), this ol,sedatives and hypnotics increase CNS depression.; Unhydrogenated ergot alkaloids increase the risk of developing peripheral circulation disorders; Sulfasalazine increases plasma concentration of bisoprolol.; Combinations that should be taken into account; Mefloquine when used simultaneously with bisoprolol may increase the risk of bradycardia. MAO inhibitors (with the exception of MAO inhibitors of type B) can enhance the antihypertensive effect. Simultaneous use can lead to the development of hypertensive crisis.; Ergotamine increases the risk of developing disorders of the peripheral circulation.; Rifampicin shortens T1 / 2 bisoprolol.
special instructions
Do not abruptly interrupt treatment with the drug Byol; due to the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose by 25% every 3-4 days.; Monitoring the condition of patients taking the drug Byol; should include measurement of heart rate and blood pressure (at the beginning of treatment - daily, then - once every 3-4 months), conducting ECG, determination of blood glucose concentration in patients with diabetes mellitus (1 time in 4-5 months); It is recommended to monitor kidney function in elderly patients (1 time in 4-5 months); Patients should be trained in how to calculate heart rate and instruct medical consultation with a heart rate less than 50 beats / min.; If a patient is detected Elderly patients with increasing bradycardia (heart rate less than 50 beats / min), marked reduction of blood pressure (systolic blood pressure less than 100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue treatment. external respiration in patients with a burdened bronchopulmonary history.; Patients using contact lenses should take into account that, while the drug is being treated, it is possible to reduce the production of tear fluid; Byol; patients with pheochromocytoma are at risk of developing paradoxical arterial hypertension (unless effective blockade of β-adrenoreceptors is previously achieved); In hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because it can enhance symptoms. In diabetes mellitus, bisoprolol can mask tachycardia caused by hypoglycemia.Unlike non-selective beta-adrenergic blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood to a normal level. When used simultaneously, clonidine can be stopped only a few days after discontinuation of the drug Byol; hypersensitivity reactions and the lack of effect of the usual doses of epinephrine against the background of an aggravated allergic history. In the case of the need for surgery In the meantime, the drug is discontinued 48 hours before general anesthesia begins. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with a minimally negative inotropic effect.; The reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg). Drugs that reduce catecholamine stores (in . reserpine), can enhance the action of beta-blockers, so patients taking such combinations of drugs should be under the constant supervision of a physician to detect a pronounced decrease in blood pressure or bradycardia.; Patients with bronchospastic diseases can be carefully prescribed cardioselective beta; blockers in case of intolerance and / or ineffectiveness of other antihypertensive drugs. While receiving; beta-adrenergic blockers in patients with concomitant bronchial asthma, airway resistance may increase. If you exceed the dose of the drug Byol; in such patients there is a risk of developing bronchospasm.; In case of an increase in bradycardia (HR less than 50 beats / min), a pronounced decrease in blood pressure (systolic blood pressure less than 100 mm Hg), AV blockade is necessary, reduce the dose or stop treatment. It is recommended to stop therapy with Byol; with the development of depression.; You can not abruptly interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction. The abolition of the drug 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 the study of the concentration in the blood and urine of catecholamines, normetanephrine, vanillin almond acid,titers of antinuclear antibodies.; In smoking patients, the effectiveness of beta-blockers is lower.; Effect on ability to drive vehicles and control mechanisms; During the period of treatment with Byol; Care must be taken when driving and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.