Expiration date: 02/2025

The composition and form of issue: 

Tablets, film-coated. 1 tablet contains hemifumarate bisoprolol 5 or 10 mg

excipients: starch crospovidone Pregelatinised microcrystalline silica colloidal anhydrous magnesium stearate macrogol 6000 titanium dioxide (E171) talc colorant iron (III) oxide yellow (E172) hypromellose (HPMC) 

blistere in 10 PCs per cartons 3 or 5 blisters.

Description pharmaceutical form:

Tablets 5 mg: round tablets, film-coated light yellow in color, with one side convex, the other — risk, the tablet surface is beveled to risk.

Tablets 10 mg: round tablets, film-coated from yellow to orange in color, with one side convex, the other — risk, the tablet surface is beveled to risk.

Feature:

Selective beta1-blocker (cardioselective) without internal sympathomimetic activity and membrane stabilizing properties.

Pharmacokinetics:

Absorption is 80-90%, eating does not affect the absorption. Cmax in plasma observed after 1-3 hours, tying with blood plasma proteins — about 30%. The permeability of the BBB and placental barrier — low, the secretion of breast milk — low.

50% of the dose is metabolized in the liver to form inactive metabolites, a 50% excreted by kidneys unchanged. T1/2 is 10-12 hrs

Description pharmacological action:

Selective beta1-blocker without own sympathomimetic activity, has membrane stabilizing effect. Reduces renin activity of blood plasma, reduces the need of myocardium in oxygen, slows 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 effect.

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 beta-adrenergic receptors), which, through 1-3 day returns to the source, and at long — decreases.

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 of baroreceptors in response to changes in 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 in oxygen as a result of deceleration of 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 anterograde 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, causes a delay of sodium ions (Na+) in the body the severity of the atherogenic actions is not different from the action of propranolol.

Indications:

• hypertension
  
• Coronary artery disease (prevention of angina attacks).
  

Contraindications:

• hypersensitivity to the drug and other beta-blockers
  
• shock (including cardiogenic) collapse
  
• pulmonary edema, acute heart failure, chronic heart failure decompensation
  
• AV blockade II art., sinoatrial block, sick sinus syndrome node
  
• bradycardia
  
• Prinzmetal's angina
  
• cardiomegaly (with no signs of heart failure)
  
• hypotension (SBP <100 c="" p="">
  
• severe forms of bronchial asthma and other obstructive diseases of the respiratory tract
  
• concomitant use of monoamine oxidase inhibitors (MAOIS) (with the exception of MAO inhibitors)
  
• late stages of peripheral circulatory disorders, Raynaud's disease,
  
• pheochromocytoma (without the simultaneous use of alpha-blockers)
  
• metabolic acidosis
  
• depression
  
• the age of 18 years (efficacy and safety not established).
  

With caution:

• liver failure
  
• chronic renal failure
  
• myasthenia gravis
  
• thyrotoxicosis
  
• diabetes
  
• AV blockade I of a degree
  
• depression in history
  
• psoriasis
  
• allergic reactions in anamnesis
  
• old age.
  

Application of pregnancy and breast-feeding:

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.

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, convulsions.

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), the 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, laringo - and bronchospasm when administered in high doses (loss of selectivity) in predisposed patients.

From the endocrine system: hyperglycemia (in patients with insulin-independent diabetes mellitus), hypoglycemia (in patients, receiving insulin), hypothyroid state.

Allergic reactions: skin itching, rash, hives.

With the skin: increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions, exacerbation of psoriasis, alopecia.

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: back pain, arthralgia, cramps in the calf muscles, reduced libido, reduced potency, the syndrome (increased angina, increased blood pressure).

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.

Radiopaque iodine-containing 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 (blockade of PG synthesis by the kidney, delay Na+), corticosteroids and estrogens (delay of Na+ions).

Cardiac glycosides, methyldopa, reserpine, and guanfacine, CCB (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or exacerbating bradycardia, AV block, cardiac arrest and heart failure.

Nifedipine can lead to significant reduction of AD.

Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs can lead to 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.

Sulfasalazine bisoprolol improves concentration in plasma rifampicin shortens the half-life.

Method of application and dose:

Inside, in the morning on an empty stomach, without chewing. 5 mg 1 time per day, If necessary dose increased to 10 mg 1 time per day. The maximum daily dose of 20 mg/day.

In patients with impaired kidney with Cl creatinine <10 20="" p="">

Dose adjustment in elderly patients is not required.

Overdose:

Symptoms: 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 adsorbing drugs symptomatic therapy: with advanced 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 no signs of pulmonary edema — in/in the introduction of plasma-substituting solutions in case of inefficiency — epinephrine, dopamine, dobutamine (to maintain Chrono- and inotropic action and the elimination of expressed lower AD) heart failure — cardiac glycosides, diuretics, glucagon in convulsions — in/diazepam with bronchospasm — beta2-agonists inhalation.

Special instructions:

Control for patients receiving bisoprolol should include measurement of heart rate and blood pressure (at the beginning of treatment — daily, then 1 once in 3-4 mo), the 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 heart rate <50 p="">

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 <100 p="">

In smokers 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 epinephrine with aggravated allergic anamnesis.

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 pick up the drugs for General anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate/atropine (1-2 mg).

Drugs, 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 (<50 100="" av="" p="">

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 (25% in 3-4 day). Should be lifted before the examination of blood and urine catecholamines, normetanephrine and vanillylmandelic acid, titles of antinuclear antibodies.

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.