Expiration date: 07/2025
Release form and composition:
Tablets, film-coated from beige-yellow to beige, round, lenticular to break white or nearly white.
1 tablet contains bisoprolol fumarate 2.5, 5 or 10 mg
Excipients: croscarmellose sodium (Primerose), povidone (polyvinylpyrrolidone middle), pregelatinized starch (starch 1500), colloidal silicon dioxide (Aerosil), talc, cellulose microcrystalline, lactose (milk sugar), magnesium stearate.
The composition of the film shell: Opadry II (polyvinyl alcohol, partly hydrolyzed, titanium dioxide, talc, macrogol (polyethylene glycol 3350), dye iron oxide (II)).
Pharmacological action:
Selective beta1-blocker without own sympathomimetic activity, has membrane stabilizing effect. Reduces renin activity of blood plasma, reduces the need heart of oxygen, reduces the heart rate (at rest and during exercise).
It has hypotensive, antiarrhythmic and antianginal effects. Blocking in low doses beta1-adrenergic receptors of the heart, reduces catecholamines stimulated camp formation from ATP, reduces intracellular current of calcium ions, has a negative Chrono-, dromo-, batmo - and inotropic action, oppressing conductivity and anxiety attacks, reduces AV conduction.
With increasing doses above the therapeutic having beta2-adrenoblokirtee action.
The CSO at the beginning of the drug in the first 24 h, increases (as a result of reciprocal increase in activity of alpha-adrenergic receptors and eliminate stimulation of beta2-adrenergic receptors), which, through 1-3 day returns to the source, and prolonged assignment is reduced.
Hypotensive effect is associated with a decrease in minute volume of blood, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (is of great significance for patients with initial hypersecretion of renin), restoring sensitivity in response to decreased blood pressure and effects on the Central nervous system. In arterial hypertension effect occurs in 2-5 days, stable effect - in 1-2 months.
Antianginal effect is due to reduction of requirement of a myocardium for oxygen by reducing the heart rate and decrease contractility, lengthening of diastole, improved myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of the muscle fibers of the ventricles can increase oxygen demand, especially in patients with chronic heart failure.
Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased camp content, arterial hypertension), decrease in speed spontaneous initiation sinusnogo and ectopiceski drivers rhythm and slowing AV conduction (mainly in the antegrade and to a lesser extent, in the retrograde directions through the AV node) and on additional ways.
When used in high therapeutic doses, unlike nonselective beta-blockers, has a less pronounced effect on bodies containing beta2-adrenergic receptors (pancreas, skeletal muscle, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause the delay of sodium ions (Na+) in the body the severity of the atherogenic actions is not different from the action of propranolol.
Pharmacokinetics:
Absorption and distribution
Absorption is 80-90%, eating does not affect the absorption. Cmax in plasma is after 1-3 h.
Relationship with blood plasma proteins - about 30%. Passes through GEB and placental barrier to a minor degree, in small amounts excreted in breast milk.
Metabolism and excretion
50% of the dose is metabolized in the liver to form inactive metabolites.
T1/2 is 10-12 hrs About 98% is excreted with urine - 50% in unaltered, less 2% - with bile.
Indications:
— arterial hypertension
— Coronary artery disease: prevention of angina attacks.
Dosing regimen:
The drug is taken orally in the morning on an empty stomach, without chewing, in the initial dose of 5 mg 1 times/day. If necessary, increase the dose to 10 mg 1 times/day. The maximum daily dose of 20 mg/day.
In patients with impaired renal function when KK less 20 ml/min or with acute human liver the maximum daily dose should be 10 mg.
Dose adjustment in elderly patients is not required.
Side effects:
CNS: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor.
From the sensory organs: impaired vision, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis.
From the side of cardiovascular system: sinus bradycardia, palpitations, impaired conductivity infarction, AV -blockade (up to the development of a complete transverse blockade and heart failure), arrhythmia, weakening of myocardial contractility, development (the aggravation of) chronic heart failure (swelling of ankles, feet, shortness of breath), reducing AD, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disorders, cold lower extremities, Raynaud's syndrome), chest pain.
From the digestive system: dry mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, the human liver (dark urine, yellowness of the sclera or skin, cholestasis), changing taste.
The respiratory system: nasal congestion, difficulty breathing in the appointment of high doses (loss of selectivity) and/or prone patients - laringo - and bronchospasm.
From the endocrine system: hyperglycemia (in patients insulinnezawisimam diabetes mellitus), hypoglycemia (in patients, receiving insulin), hypothyroid state.
Allergic reactions: skin itching, rash, hives.
Dermatological reactions: increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions, exacerbation of psoriasis symptoms.
From the laboratory parameters: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, change of enzyme activity in the liver (increased ALT, AST), bilirubin, triglycerides.
Effect on fetus: intrauterine growth retardation, hypoglycemia, bradycardia.
Other: pain in the back, artralgia, reduced libido, reduced potency, the syndrome (increased angina, increased blood pressure).
Contraindications:
— shock (including cardiogenic)
— the collapse
— pulmonary edema
acute heart failure
— chronic cardiac insufficiency of the decompensation
— AV blockade II and III degree
— sinoatrial block
— SSSU
— severe bradycardia
— Prinzmetal's angina
— cardiomegaly (with no signs of heart failure)
— hypotension (systolic BP less than 100 mm Hg.St., especially in myocardial infarction)
— severe forms of asthma and chronic obstructive pulmonary disease in anamnesis
— simultaneous reception of MAO inhibitors (except MAO-B)
— late stages of peripheral circulatory disorders, Raynaud's disease,
— pheochromocytoma (without the simultaneous use of alpha-blockers)
— metabolic acidosis
— the age 18 years (effectiveness and safety have not been established)
— hypersensitivity to the medication and other beta-blockers.
With caution should designate product in liver failure, chronic renal insufficiency, myasthenia gravis, thyrotoxicosis, diabetes, AV blockade degree I, depression (including in history), psoriasis, as well as elderly patients.
Pregnancy and lactation:
Use in pregnancy and lactation is possible only if the benefit to the mother outweighs the risk of side effects in the fetus and child.
Special instructions:
Control for patients receiving Bisoprolol should include measurement of HR and AD (at the beginning of treatment - daily, then 1 once in 3-4 months), ECG, determination of blood glucose in patients with diabetes mellitus (1 once in 4-5 mo). In elderly patients it is recommended to monitor kidney function (1 once in 4-5 mo).
Should teach the patient methods of calculating heart rate and instruct on the need of medical advice in the heart rate less than 50 beats/min.
Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.
About 20% patients with stroke beta-adrenoblokatora ineffective. The main reason - severe coronary atherosclerosis with the low threshold of ischemia (heart rate less than 100 beats/min) and increased end-diastolic volume of the left ventricle that violate the upper subendocardialnah blood flow.
Smoking patients the effectiveness of beta-adrenoblokatorov below.
Patients using contact lenses should take into account that the treatment may decrease the production of tear fluid.
When used in patients with pheochromocytoma there is a risk of paradoxical hypertension (if not previously achieved effective alpha adrenoblokada).
Thyrotoxicosis Bisoprolol can mask certain clinical signs of hyperthyroidism, e.g., tachycardia. Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, because it can reinforce the symptoms.
At diabetes can mask the tachycardia, caused by hypoglycemia. Unlike nonselective beta-blockers hardly enhances insulin-induced hypoglycemia and delay recovery of the glucose concentration in the blood to normal levels.
At the same time taking clonidine its reception can be terminated only a few days after discontinuation of Bisoprolol.
Perhaps the increased severity of hypersensitivity reactions and lack of effect of conventional doses of spinnerin with aggravated allergologicaki history. In case of the need for planned surgical treatment elimination of the drug is carried out for 48 h before General anesthesia. If the patient has taken the drug before surgery, he should choose drug for General anesthesia with minimal negative inotropic effects.
Reciprocal activation of the vagus nerve can eliminate/atropine (1-2 mg).
Medicines, reducing stocks of catecholamines (e.g. reserpine), may enhance the action of beta-adrenoblokatorov, therefore, patients, accepting such combination drugs, should be under constant supervision of a doctor to identify expressed downward AD or bradycardia.
Patients with bronchospastic diseases you can assign a cardioselective blocker in case of intolerance and/or ineffectiveness of other antihypertensive drugs. Overdose is dangerous development of bronchospasm.
In the case of elderly patients increasing bradycardia (less 50 beats/min), a pronounced lowering of blood pressure (systolic BP below 100 mm Hg.St.), AV-blockade, it is necessary to reduce the dose or stop the treatment.
It is recommended to discontinue therapy in the development of depression.
Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. Lifting a gradually reducing the dose over 2 weeks or more (reduce the dose 25% in 3-4 day). Should be lifted before the examination of blood and urine catecholamines, normetanephrine and vanillylmandelic acid, titles of antinuclear antibodies.
Effects on ability to drive vehicles and management mechanisms
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.
Overdose:
Symptoms: arrhythmia, ventricular arrythmia, expressed aetiology, AV-blockade, expressed lower AD, chronic heart failure, cyanosis of nails of fingers or palms, difficulty in breathing, bronchospasm, dizziness, fainting, seizures.
Treatment: gastric lavage and the appointment of adsorbents, symptomatic therapy: when developed AV blockade - in/in the introduction 1-2 mg of atropine, epinephrine or staging a temporary pacemaker with ventricular arrhythmia - lidocaine (class IA drugs do not apply ) while reducing AD - the patient should be in Trendelenburg position if there are no signs of pulmonary edema - in/in plasma-substituting solutions in case of inefficiency - epinephrine, dopamine, dobutamine (for maintaining chronotropic and inotropic actions and resolve expressed lower AD) in heart failure - cardiac glycosides, diuretics, glucagon in convulsions - in/diazepam with bronchospasm beta-agonists inhalation.
Drug interactions:
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 drugs for at/in the introduction increases the risk of anaphylactic reactions.
Phenytoin in the on/in the introduction, drugs for inhalation General anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive actions and reduce the likelihood of AD.
Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, the AD).
Reduces the clearance of lidocaine and xantinov (except difillina) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of Smoking.
Gipotenzivny effect NPVS weaken (delay of Na+ and the blockade of prostaglandin synthesis by the kidney), corticosteroids and estrogens (delay of Na+ions).
Cardiac glycosides, methyldopa, reserpine, and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or exacerbating bradycardia, AV-blockade, heart failure and heart failure.
Nifedipine can lead to significant reduction of AD.
Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive medicines can cause excessive reduction of AD.
Prolongs the action of non-depolarizing muscle relaxants and anticoagulant effect of coumarins.
Three - and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics drugs increase oppression CNS.
Not recommended simultaneous application with MAO inhibitors because of significant increase gipotenzivnogo actions, break in treatment between receiving MAO inhibitors and bisoprolol must be not less than 14 days.
Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.
Ergotamine increases risk of peripheral circulation sulfasalazine bisoprolol improves concentration in plasma rifampicin shortens the half-life.
Terms and conditions of storage:
List B. the Drug should be stored in a dry, dark, inaccessible to children place at temperature not exceeding 25°C. shelf Life - 3 years.
