More info
Active ingredients
Bisoprolol
Release form
Pills
Composition
Bisoprolol hemifumarate 5 mg adjuvants: microcrystalline cellulose - 20 mg, calcium hydrophosphate - 51.8 mg, corn starch - 5 mg, croscarmellose sodium - 1.7 mg, magnesium stearate - 0.75 mg, anhydrous colloidal silicon dioxide - 0.75 mg., The composition of the shell: 1.24 mg, hypromellose - 0.96 mg, titanium dioxide - 0.9 mg, macrogol 4000 - 0.34 mg, iron dye (iii) yellow oxide - 0.06 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 antihypertensive, antiarrhythmic and antianginal effects. By blocking low-dose β1-adrenoreceptors of the heart, 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. OPS at the beginning of the drug, in the first 24 hours, increases (as a result of a reciprocal increase in the activity of α-adrenoreceptors and the elimination of stimulation of β2-adrenoreceptors), which after 1-3 days returns to its original value, and with prolonged use - decreases. 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 effectiveness in response to lower blood pressure and effects on the central nervous system. In case of arterial hypertension, the effect occurs after 2-5 days, a stable effect is observed after 1-2 months. The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in contractility and other myocardial functions, a longer diastole, and an 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,It has a less pronounced effect on organs containing β2-adrenoreceptors (pancreas, skeletal muscle, smooth muscle of peripheral arteries, bronchi and uterus) and on 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 of bisoprolol is almost completely absorbed from the gastrointestinal tract, food intake does not affect absorption. Bioavailability is about 90%. Tmax in blood plasma - 2-4 hours after ingestion. Distribution and metabolismBinding to plasma proteins - 26-33%. Metabolized in the liver, the metabolites of bisoprolol do not possess pharmacological activity. The permeability through the BBB and the placental barrier is low, in small quantities excreted in breast milk. Excretion of T1 / 2 is 9-12 h, 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; - ischemic heart disease: 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 II and III degree blockade (without pacemaker); - sinoatrial blockade; - sick sinus syndrome; HR prior to treatment less than 50 beats / min); - severe arterial hypotension (systolic blood pressure less than 100 mm Hg); - cardiomegaly (without signs of heart failure); - severe forms of bronchial asthma and COPD in history; peripheral blood circulation; Raynaud's syndrome; metabolic acidosis; pheochromocytoma (without simultaneous use of alpha-adrenergic blockers); concomitant use of floctafenin and sultopride; not 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 x ways); - desensitization therapy; - hyperthyroidism; - sugartype 1 diabetes and diabetes mellitus with significant fluctuations in glucose concentration in the blood; severe renal failure (CC less than 20 ml / min); severe dysfunction of the liver; general anesthesia; - myasthenia; - AV block I degree; - Prinzmetal's angina; - restrictive cardiomyopathy; - congenital heart defects or valvular heart disease with severe hemodynamic disorders; - chronic heart failure with heart attack. iocardium during the last 3 months; - depression (including history); - pheochromocytoma (simultaneous use of alpha-blockers); - strict diet; - allergic reactions in history.
Precautionary measures
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
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 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 the baby.In the case when treatment with Byol is considered necessary, the blood flow 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 with regard to pregnancy and / or the fetus, alternative methods of therapy should be taken. 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 is not recommended for women during lactation. If necessary, the use of the drug during lactation, breastfeeding should be stopped.
Dosage and administration
Byol is taken orally, in the morning on an empty stomach, 1 time per 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 physician takes each patient individually and the dosage regimen and dose, in particular, taking into account the heart rate and the patient's condition. Byol is administered 5 mg once a day for hypertension and IBSP. If necessary, the dose is increased to 10 mg 1 time / day. When treating hypertension and angina, the maximum daily dose is 20 mg 1 time / day. Chronic heart failure (CHF) Starting treatment for CHF with Byol requires a special titration phase and regular medical monitoring A prerequisite for treatment with Byol is stable CHF with no signs of exacerbation. Treatment of CHF with Byol begins in accordance with 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 at the initial stages of treatment, it is recommended to use the drug in smaller doses. The recommended initial dose is 1.25 mg (1/4 tab. 5 mg) 1 time / 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. .on 10 mg), 7.5 mg (3/4 tab. on 10 mg) and 10 mg 1 time / day with an interval of not less than 2 or more weeks. 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. During the titration, regular monitoring of blood pressure, heart rate and symptoms of increasing CHF severity is recommended. The worsening of CHF symptoms is possible already from the first day of the drug use. During the titration phase or after it, a temporary worsening of the CHF course, 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. It may also require a temporary dose reduction of Byol 5 mg each or cancellation of treatment. After stabilization of the patient's condition, the dose should be re-titrated or continued treatment. Disruption of renal or hepatic function Disorders of mild or moderate liver function usually do 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 do not need dose adjustment. There is currently insufficient 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 caused 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 messages). For the cardiovascular system: very often - a decrease in heart rate (bradycardia, especially in patients with CHF), a heartbeat; often - a pronounced decrease in blood pressure (especially in patients with CHF), the manifestation of angiospasm (increased disturbances of peripheral circulation,feeling cold in the limbs (paresthesia); rarely - a violation of 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 disturbances, depression, anxiety; rarely - confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremor, muscle cramps. Typically, these phenomena are mild in nature 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, hearing loss , earache; very rarely - dryness and soreness of the eyes, conjunctivitis, taste disturbances. On the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or obstructive respiratory diseases; rarely, allergic rhinitis; nasal congestion. From 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 of libido. From the laboratory indicators: 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 skin side: rarely - increased sweating, skin flushing, exanthema, psoriasis-like skin reactions; very rarely - alopecia, beta-blockers can exacerbate the course of psoriasis. Others: withdrawal syndrome (an increase in angina 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. Treatment: first of all, you should stop taking the drug, wash the stomach It is necessary to accept the adsorbing means, to carry out 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 should be monitored constantly and treated 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 (i.e., non-prescription drugs). Recommended combinations Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) while use with bisoprolol can reduce AV conductivity and myocardial contractility. Blockers of slow calcium channels (BMCC), such as verapamil and, to a lesser extent, diltiazem, while using with bisoprolol can lead to a decrease in myocardial contractility and disruption of AV conduction. In particular, i.v. administration of verapamil to patients taking beta-blockers may result in marked arterial hypotension and AV blockade. Central-acting antihypertensive drugs (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to decompensation of CHF due to a decrease in HR and reduce cardiac output, as well as to the appearance of symptoms of vasodilation due to a decrease in central sympathetic tone. Combinations requiring special careBMCC derivatives of dihydropyridine (for example, nifedipine, felodipi 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 ruled out. Class III antiarrhythmic drugs (eg, amiodarone) may exacerbate the disturbance of AV conduction. The effect of beta-blockers for local use (eg, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol : a pronounced decrease in blood pressure, a decrease in heart rate. Parasympathomimetics with simultaneous use with bisoprolol may increase the disturbance of AV conduction and increase the risk of developing bradycardia. Simultaneously The use of bisoprolol with beta-adrenomimetics (for example, isoprenaline, dobutamine) can reduce the effect of both drugs. The combination of bisoprolol with adrenomimetics that affect the β- and α-adrenoreceptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these drugs arising with participation of α-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 radiopaque diagnostic agents for intravenous administration increase the risk of development anaphylactic reactions. Phenytoin with a / in the introduction, means for inhalation anesthesia (derivatives of hydrocarbons) increase the expression to effect of insulin and hypoglycemic agents for oral administration may vary with treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure). Clearance of lidocaine and xanthines (except for theophylline) may decrease due to a possible increase in their concentration of plasma blood, especially in patients with initially increased clearance of theophylline under the influence of smoking. The antihypertensive effect weakens NSAIDs (sodium ion retention and synthesis blockade is simple Lundeen kidneys), SCS and estrogens (delay sodium ions) .Serdechnye glycosides increase the risk of developing or worsening bradycardia, AV-blockade of cardiac arrest and cardiac nedostatochnosti.Diuretiki, clonidine, sympatholytic,hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure. The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins during treatment with bisoprolol can be prolonged. increase the risk of developing peripheral circulatory disorders. Sulfasalazine increases the concentration of bisoprolol in the blood plasma. The combination that Mefloquine should be taken into account while using it with bisoprolol may increase the risk of developing bradycardia. MAO inhibitors (with the exception of MAO inhibitors of type B) may 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 of bisoprolol.
special instructions
Do not abruptly interrupt the treatment with the drug Byol because of 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 measuring heart rate and blood pressure (at the beginning of treatment - daily, then 1 time every 3-4 months), 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). It is necessary to teach the patient how to calculate heart rate and instruct him about the need for medical consultation less than 50 bpm. In case of detection in a patient advanced bradycardia (HR less than 50 beats / min), pronounced decrease in blood pressure (systolic blood pressure less than 100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue treatment. in patients with a burdened bronchopulmonary history. Patients using contact lenses should take into account that with the treatment with a drug, there is a decrease in the production of tear fluid. When using the drug Byol, patients with pheochromocytoma are at risk development of paradoxical arterial hypertension (unless an effective blockade of α-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 the symptoms. In case of diabetes mellitus, bisoprolol may mask the 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 clonidine is taken simultaneously, it can be stopped only a few days after discontinuation of Byol. and the lack of effect of the usual doses of epinephrine on the background of burdened allergological anamnesis. If necessary, a surgical intervention After the drug has been discontinued, 48 hours before the start of general anesthesia. If the patient took 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 atropine (1-2 mg). Drugs that reduce catecholamine stores . 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 radikardii.Patsientam with bronhospasticheskimi diseases can be prescribed with care cardioselective beta-blockers in the case of intolerance and / or ineffectiveness of other antihypertensive agents. In patients with concomitant bronchial asthma, the resistance of the respiratory tract can be enhanced against the background of adrenergic blockers. If you exceed the dose of the drug Byol in these 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 reduce the dose or discontinue treatment. It is recommended to stop therapy with Byol when depression develops. 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-malic acid, titers of antinuclear antibodies. Smoking patients the effectiveness of beta-blockers below. Effect on the ability to drive vehicles and control mechanisms. During the period of treatment with Byol, care must be taken when driving and occupying others with potential. but hazardous activities that require high concentration and psychomotor speed reactions.