Bisoprolol-LF tab. p/o 5mg №15х4

Name:
Bisoprolol-LF
Description:
Round tablets 2.5 mg, film-coated, white, biconvex shape. Round tablets 5 mg and 10 mg, film-coated yellow, biconvex shape. Release form Film-coated tablets. Dosage 5 mg: 10 or 15 tablets in a blister pack. Three or five blister packs of 10 tablets; two or four blister packs of 15 tablets together with instructions for medical use in a pack of cardboard. Dosage 10 mg: 10 or 15 tablets in a blister pack. Three, five or six blister packs of 10 tablets each; four blister packs of 15 tablets, together with instructions for medical use in a pack of cardboard. Dosage 2.5 mg: 10 or 15 tablets in a blister pack. Three, five or six blister packs of 10 tablets each; two or four blister packs of 15 tablets together with instructions for medical use in a pack of cardboard. Pharmacodynamics Bisoprolol is a selective beta1-blocker without its own sympathomimetic and significant membrane stabilizing activity; It has antihypertensive, antiarrhythmic and antianginal effects. Blocking beta1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces intracellular Ca2+ current, has a negative chrono-, dromo-, batmo- and inotropic effect (slows down the heart rate (HR), inhibits conductivity and excitability, reduces myocardial contractility). With increasing doses, it has a beta2-blocking effect. The total peripheral vascular resistance (TPVR) at the beginning of the use of beta-blockers in the first 24 hours increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which after 1-3 days returns to the original, and decreases with long-term administration . The maximum effect of the drug is achieved 3-4 hours after ingestion. With the appointment of bisoprolol 1 time per day, its therapeutic effect persists for 24 hours due to the 10-12-hour half-life from blood plasma. The hypotensive effect is associated with a decrease in the minute volume of blood (MBC), sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (RAAS) (it is more important for patients with initial renin hypersecretion), restoration of the sensitivity of baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure (BP)) and the effect on the central nervous system (CNS). With arterial hypertension, the effect occurs after 2-5 days. As a rule, the maximum reduction in blood pressure is achieved 2 weeks after the start of treatment. The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and a decrease in contractility, a prolongation of 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, it can increase the need for oxygen, especially in patients with chronic heart failure (CHF). The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in atrioventricular (AV) conduction (mainly in antegrade and, to a lesser extent, in retrograde directions). through the AV node) and along additional pathways. Unlike non-selective beta-blockers, when administered in medium therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause Na+ retention. in the body; the severity of the atherogenic action does not differ from the action of propranolol. When used in high doses, it has a blocking effect on both subtypes of beta-adrenergic receptors. Pharmacokinetics Absorption Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Bioavailability, due to negligible first pass metabolism through the liver (approximately 10%), is about 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol is characterized by linear kinetics, and plasma concentrations are proportional to the dose taken from 5 to 20 mg. Cmax in blood plasma is reached in 2-3 hours. Distribution Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. Communication with plasma proteins reaches approximately 30%. Metabolism Bisoprolol is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water soluble) and excreted by the kidneys. The main metabolites found in plasma and urine do not show pharmacological activity. The data obtained as a result of experiments with human liver microsomes in vitro show that metabolism is carried out primarily with the help of the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays a minor role. Withdrawal The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism by the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15 l / h. T1 / 2 is 10-12 hours. Pharmacokinetics in special clinical situations There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concurrent impairment of liver or kidney function. Indications for use arterial hypertension; ischemic heart disease (stable angina). Dosing and Administration Tablets should be taken orally once a day – in the morning, before breakfast, during or after it, with a small amount of liquid. Tablets should not be chewed or crushed into powder. In all patients, the dose is selected individually, primarily taking into account the heart rate and the patient’s condition, treatment should be started with a low dose and gradually increased, if necessary. Treatment of arterial hypertension: The recommended dose is 5 mg 1 time / day. In mild forms of hypertension (diastolic pressure up to 105 mm Hg), 2.5 mg 1 time / day may be sufficient. If necessary, the dose can be increased to 10 mg 1 time / day. A subsequent dose increase is justified only in exceptional cases. The maximum daily dose is 20 mg 1 time / day. Treatment of coronary heart disease (angina pectoris): The recommended dose is 5 mg 1 time / day. If necessary, the dose can be increased to 10 mg 1 time / day. A subsequent dose increase is justified only in exceptional cases. The maximum daily dose is 20 mg 1 time / day. Duration of treatment The duration of treatment is not limited in time and depends on the type and severity of the disease. Treatment with the drug – especially in patients with coronary heart disease – should not be abruptly stopped, as this may lead to an exacerbation of the disease. If it is necessary to stop treatment, the dose should be reduced gradually (for example, halving the dose at weekly intervals). Special groups of patients Impaired renal and hepatic function In patients with impaired hepatic or renal function (mild or moderate), adjustment of the dosing regimen is usually not required. In patients with severe renal insufficiency (creatinine clearance < 20 ml / min) and patients with severely impaired liver function, the maximum daily dose should not exceed 10 mg. Increasing the dose in such patients should be done with extreme caution. The experience of using the drug in patients on hemodialysis is limited, but there is no evidence of the need to change the dosing regimen. Elderly No dose adjustment is required. Children It is not recommended to use the drug in pediatrics, due to the lack of sufficient data on the use of the drug in children. Use during pregnancy and lactation During pregnancy, the drug Bisoprolol-LF should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and / or child. 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. Bisoprolol may have a negative effect on the course of pregnancy and / or the fetus / newborn. β-blockers reduce placental perfusion, which can cause growth retardation, fetal death, abortion, or preterm birth. The fetus / newborn may experience side effects when using bisoprolol (for example, hypoglycemia and bradycardia). In the case of the use of pregnant bisoprolol, newborns should be observed during the first 3 days, because. hypoglycemia and bradycardia may occur. Bisoprolol should not be used during lactation. The excretion of bisoprolol in the milk of lactating women has not yet been studied. In animal experiments, no more than 2% of the dose was found in milk. Precautions Do not stop treatment abruptly and do not change the recommended dosage without first consulting your 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 CAD. If discontinuation of treatment is necessary, the dosage should be reduced gradually. Monitoring of patients taking Bisoprolol-LF should include monitoring of heart rate and blood pressure (at the beginning of treatment - daily, then 1 time in 3-4 months), ECG, blood glucose in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended to monitor kidney function (1 time in 4-5 months). The patient should be taught how to calculate heart rate and instruct about the need for medical advice if the heart rate is less than 50 beats / min. The drug should be used with caution in the following cases: - Diabetes mellitus with significant fluctuations in blood glucose concentration: symptoms of a pronounced decrease in glucose concentration (hypoglycemia) such as tachycardia, palpitations or excessive sweating may be masked; - Strict diet; - Carrying out desensitizing therapy; - AV block I degree; - Prinzmetal's angina; - Violations of the peripheral arterial circulation of mild to moderate degree (at the beginning of therapy, there may be an increase in symptoms); - Psoriasis (including history). Respiratory system: in bronchial asthma or COPD, the simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, an increase in airway resistance is possible, which requires a higher dose of beta2-agonists. Allergic reactions: beta-blockers, including the drug Bisoprolol-LF, may 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. Therapy with epinephrine (adrenaline) does not always give the expected therapeutic effect. General anesthesia: when performing general anesthesia, the risk of blockade of beta-adrenergic receptors should be taken into account. If it is necessary to stop therapy with Bisoprolol-LF before surgery, this should be done gradually and completed 48 hours before general anesthesia. You should warn the anesthesiologist that you are taking Bisoprolol-LF. Pheochromocytoma: in patients with a tumor of the adrenal glands (pheochromocytoma), the drug Bisoprolol-LF can be prescribed only against the background of the use of alpha-blockers. Hyperthyroidism: during treatment with Bisoprolol-LF, symptoms of hyperthyroidism (hyperthyroidism) may be masked. Influence on the ability to drive vehicles or potentially dangerous 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 work with technically complex mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, when changing the dose, and also with the simultaneous use of alcohol. Interaction with other drugs The effectiveness and tolerability of bisoprolol may be affected by the simultaneous use of other drugs. Such an interaction can also occur if there was a short period of time between medications. It is necessary to inform the doctor about taking other medicines, including medicines purchased without a prescription. Combinations that are not recommended: - Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): may increase the negative effect on AV conduction and myocardial inotropic function. - Calcium antagonists such as verapamil, to a lesser extent - diltiazem: a negative effect on myocardial contractility and AV conduction. Intravenous administration of verapamil can lead to severe hypotension and atrioventricular block in patients taking beta-blockers. - Antihypertensive drugs with a central mechanism of action (clonidine, methyldopa, moxonidine, rilmenidine): concomitant use may lead to worsening of heart failure. In combination therapy, the sudden withdrawal of these agents may increase the risk of reflex hypertension. Combinations requiring special caution: - Calcium antagonists such as dihydropyridine (eg nifedipine, felodipine, amlodipine): may increase the risk of arterial hypotension. The possibility of an increase in the negative effect on the inotropic function of the myocardium in patients with heart failure is not excluded. - Class III antiarrhythmics (eg amiodarone): may increase the negative effect on AV conduction. - Parasympathomimetics: combined use may lead to an increase in AV conduction time and an increased risk of bradycardia. - Local beta-blockers (for example, contained in eye drops for the treatment of glaucoma): the effect of bisoprolol may be enhanced. - Insulin and oral hypoglycemic agents: the effect of these drugs is enhanced. Signs of hypoglycemia may be masked. Such an interaction is most likely with the use of non-selective beta-blockers. - Anesthesia: increased risk of myocardial depression and hypotension. - Cardiac glycosides (digitalis preparations): may decrease heart rate and increase AV conduction time. - Non-steroidal anti-inflammatory drugs (NSAIDs): may weaken the hypotensive effect of bisoprolol. - Beta-sympathomimetics (eg, isoprenaline, dobutamine): the use in combination with bisoprolol may lead to a decrease in the therapeutic effect of both agents. - The combination of bisoprolol with adrenomimetics that affect alpha and beta-adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs, due to the action on alpha-adrenergic receptors, leading to an increase in blood pressure. Such an interaction is more likely with the use of non-selective beta-blockers. - Antihypertensive agents, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the hypotensive effect of bisoprolol. Combinations to be considered: - Mefloquine: may increase the risk of bradycardia. - MAO inhibitors (with the exception of MAO B inhibitors) may enhance the hypotensive effect of beta-blockers. Simultaneous use can also lead to the development of a hypertensive crisis. Contraindications - acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy; - cardiogenic shock; - atrioventricular (AV) block II and III degree, without a pacemaker; - syndrome of weakness of the sinus node; - sinoatrial blockade; - severe bradycardia (heart rate less than 60 beats / minute); - severe arterial hypotension (systolic blood pressure less than 100 mm Hg); - severe forms of bronchial asthma and chronic obstructive pulmonary disease; - severe 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 (there is no sufficient data on efficacy and safety in this age group); - hypersensitivity to bisoprolol or to any of the excipients. Composition Each 2.5 mg tablet contains: active substance: bisoprolol fumarate - 2.5 mg; excipients: magnesium stearate, anhydrous colloidal silicon dioxide, crospovidone (type A), corn starch, microcrystalline cellulose, Opadry II white (talc, macrogol 4000 / PEG 4000, titanium dioxide, partially hydrolyzed polyvinyl alcohol). Each tablet 5 mg, 10 mg contains: active substance: bisoprolol fumarate - 5 mg or 10 mg; excipients: magnesium stearate, anhydrous colloidal silicon dioxide, crospovidone (type A), corn starch, microcrystalline cellulose, Opadry II yellow (talc, macrogol 4000 / PEG 4000, titanium dioxide, partially hydrolyzed polyvinyl alcohol, iron oxide yellow, quinoline yellow E104 , orange yellow E110). Overdose Symptoms: most often - AV blockade, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies greatly among individual patients and it is likely that patients with CHF are highly sensitive. Treatment: in the event of an overdose, first of all, it is necessary to stop taking the drug and start supportive and symptomatic therapy. With severe bradycardia: intravenous atropine. If the effect is insufficient, a remedy with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be required. With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions and vasopressor drugs. For AV block: Patients should be monitored closely and treated with beta-adrenergic agonists such as isoprenaline. If necessary, the setting of an artificial pacemaker. With an exacerbation of the course of CHF: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators. With bronchospasm: the appointment of bronchodilators, including beta2-agonists and / or aminophylline. With hypoglycemia: intravenous administration of dextrose (glucose). Side effects When taking the drug, there is a possibility of developing adverse reactions, which are classified by organ systems and by frequency of occurrence: very often ≥1/10, often from ≥1/100 to <1/10, infrequently from ≥1/1000 to <1/100 , rarely ≥ 1/10000 to < 1/1000, very rarely < 1/10000, including isolated reports. From the nervous system: often - dizziness, headache; rarely - loss of consciousness. From the sensory organs: rarely - visual impairment, hearing impairment, decreased secretion of lacrimal fluid (should be taken into account when wearing contact lenses); very rarely - conjunctivitis. From the side of the cardiovascular system: very often - sinus bradycardia, often - a decrease in blood pressure, manifestation of angiospasm (increased peripheral circulatory disorders, coldness of the lower extremities, paresthesia); infrequently - a violation of AV conduction, orthostatic hypotension, decompensation of CHF, peripheral edema. From the digestive system: often - dryness of the oral mucosa, nausea, vomiting, diarrhea, constipation; rarely - hepatitis. From the respiratory system: infrequently - difficulty breathing when administered in high doses (loss of selectivity) and / or in predisposed patients - laryngo- and bronchospasm; rarely - nasal congestion. From the endocrine system: hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin). On the part of the skin: rarely - hypersensitivity reaction (itching, rash, urticaria), increased sweating, skin flushing, very rarely - psoriasis-like skin reactions, exacerbation of symptoms of psoriasis, alopecia. From the musculoskeletal system: infrequently - muscle weakness, cramps in the calf muscles, arthralgia. From the genitourinary system: rarely - erectile dysfunction. Mental disorders: infrequently - sleep disorders, depression; rarely - nightmares, hallucinations. General disorders: often - asthenia, fatigue. Laboratory indicators: rarely - an increase in the activity of "liver" transaminases, an increase in the level of triglycerides, in some cases - thrombocytopenia, agranulocytosis. Others: "withdrawal syndrome" (increased angina attacks, increased blood pressure). Storage conditions In a place protected from moisture and light at a temperature not exceeding 25 ° C. Keep out of the reach of children. Shelf life 2 years. Do not use after the expiration date indicated on the package. Buy Bisoprolol-LF tab. p / o 5mg No. 15x4 Price for Bisoprolol-LF tab. p / o 5mg No. 15x4 Instructions for use for Bisoprolol-LF tab. p/o 5mg №15х4