Expiration date: 09/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains active substance: 

hemifumarate bisoprolol 5 or 10 mg

Excipients: microcrystalline cellulose calcium hydrogen phosphate maize starch croscarmellose sodium magnesium stearate silica colloidal anhydrous 

film cover: lactose monohydrate hypromellose titanium dioxide macrogol 4000 dye iron (III) oxide yellow dye iron (III) oxide red (for dosages of 10 mg) 

blistere in 10 PCs. in cardboard pack of 3, 5 or 10 blisters.

Description pharmaceutical form:

Tablets, film-coated, 5 mg: light yellow, round, biconvex, cross-scored on one side and engraved "BIS 5" on the other, on a break of white color.

Tablets, film-coated, 10 mg: yellow, round, biconvex, cross-scored on one side and engraved "BIS 10" on the other, on a break of white color.

Feature:

Selective &,beta1-blocker.

Pharmacokinetics:

Bisoprolol is almost completely absorbed from the gastrointestinal tract, food intake does not affect absorption. Bioavailability is about 90%.

Tmax 2-4 h after ingestion. Linking blood plasma proteins — 26-33%. Metabolized in the liver, bisoprolol metabolites have pharmacological activity. T1/2 is 9-12 hours, which makes possible the use of the drug 1 time per day.

Display memory — 50% in unaltered, less 2% — through the intestines.

Permeability through the blood-brain and placental barrier — low, in small amounts excreted in breast milk.

Description pharmacological action:

Bisoprolol is a selective beta1-blocker without own sympathomimetic activity, has membrane stabilizing effect. As for other beta1-blockers, the mechanism of action in hypertension is unclear. However, it is known that bisoprolol reduces the activity of renin in blood plasma, reduces the need of myocardium in oxygen, slows the heart rate. 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, inhibits all the functions of the heart, reduces AV conduction and excitability. When exceeding the therapeutic dose has 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-adrenoceptor), through 1-3 day returns to the original value, and with prolonged use decreases. The antihypertensive effect associated with a decrease in minute volume of blood, sympathetic stimulation of peripheral vessels, decreased activity of sympathoadrenal system (SAS) (of great importance for patients with baseline 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 observed after 1-2 months.

Antianginal effect is due to reduction of requirement of a myocardium for oxygen by reducing contractility and other functions of the myocardium, 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 (CHF).

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 in the body the severity of the atherogenic actions is not different from the action of propranolol.

Indications:

• hypertension
  
• Coronary artery disease (prevention of attacks of stable angina)
  
• CHF (in combination therapy).
  

Contraindications:

• hypersensitivity to the drug and other beta-blockers
  
• acute heart failure and CHF decompensation requiring inotropic therapy
  
• cardiogenic shock
  
• collapse
  
• AV blockade II–III degree, without pacemaker
  
• sinoatrial block
  
• syndrome sick sinus
  
• bradycardia (heart rate before treatment less than 50 beats/min)
  
• expressed arterial gipotenzia (sad less than 90 mm Hg.St.)
  
• cardiomegaly (with no signs of heart failure)
  
• severe forms of bronchial asthma and COPD in history
  
• expressed human peripheral blood circulation
  
• Raynaud's syndrome
  
• metabolic acidosis
  
• pheochromocytoma (without the simultaneous use of alpha-blockers)
  
• concomitant use floctafenine and sultopride
  
• the age of 18 years (efficacy and safety not established).
  

With caution:

• conduct desensitizing therapy
  
• hyperthyroidism
  
• diabetes mellitus type 1 and diabetes mellitus with considerable fluctuations of concentration of glucose in the blood
  
• expressed kidney failure (Cl creatinine less than 20 ml/min)
  
• marked disorders of liver function
  
• psoriasis
  
• AV blockade I of a degree
  
• Prinzmetal's angina
  
• restrictive cardiomyopathy
  
• congenital heart defect or heart valve with severe hemodynamic disturbances
  
• CHF with myocardial infarction within the last 3 months.
  
• depression (including in history)
  
• pheochromocytoma (required the simultaneous use of alpha-blockers)
  
• strict diet.
  

Application of pregnancy and breast-feeding:

Bisoprolol has no direct cytotoxic, mutagenic and teratogenic effects, but has pharmacological effects that may cause harmful effects on pregnancy and/or fetus, or newborn. Usually beta-blockers reduce placental perfusion, which leads to slower growth of the fetus, fetal death, miscarriage or premature birth. In the fetus and newborn may experience pathological reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.

The drug is Biological should not be used during pregnancy, use is possible in the case if the benefit to the mother outweighs the risk of side effects in the fetus and/or child. In the case where a drug treatment Byol been considered necessary, you should monitor the blood flow in the placenta and uterus, as well as to observe the growth and development of the unborn child, and in case of occurrence of adverse events in relation to pregnancy and/or fetus, the use of alternative therapies. You should carefully examine the newborn after birth. The symptoms of hypoglycaemia and bradycardia, usually occur within the first 3 days of life.

The period of breastfeeding. Data on the penetration of bisoprolol in the breast milk is not. Therefore, the use of Biological drug is not recommended for women during lactation.

If necessary, use of the drug during lactation breastfeeding should be discontinued.

Side effects:

Frequency of adverse reactions listed below is defined as follows (who classification): very often — at least 10%, often — not less than 1% but less than 10% infrequently — no more than 0.1% but less than 1% rare — at least 0.01% but less than 0.1%, very rare — less than 0.01%, including individual messages.

From the CCC: often — slowing the heart rate (bradycardia, especially in patients with CHF), palpitations often — expressed lower AD (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disorders, cold sensation in the limbs (paresthesias), rarely — violation of AV conduction (until the development of a complete transverse blockade and heart failure), arrhythmia, orthostatic hypotension, worsening of the flow of CHF with the development of peripheral edema (swelling of ankles, feet shortness of breath), chest pain.

From the nervous system: often — dizziness, headache, asthenia, fatigue, sleep disturbance, depression, anxiety, rarely — confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremor, muscle cramps. Usually these effects are mild nature and are usually within 1-2 weeks after the start of treatment.

From the sensory organs: rare — impaired vision, reduction of tearing (to consider when wearing contact lenses), tinnitus, hearing loss, ear pain very rare — dryness and soreness of eyes, conjunctivitis, taste disturbance.

The respiratory system: rare — bronchospasm in patients with bronchial asthma or obstructive Airways disease rare — allergic rhinitis nasal congestion.

From the digestive system: often — nausea, vomiting, diarrhea, constipation, dryness of the mucous membrane of the mouth, abdominal pain, rarely — hepatitis, increased activity of liver enzymes (ALT, AST), increased concentration of bilirubin, a change of taste.

From the side of musculoskeletal system: infrequently — artralgia, pain in the back.

With the genitourinary system: very rarely — violation of potency, weakening of libido.

Laboratory tests: rarely — increased concentration of triglycerides in blood in some cases — thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rare — skin itching, rash, hives.

From the skin: rarely — increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions very rarely — alopecia beta-blockers can exacerbate psoriasis.

Other: the syndrome (the strokes, the AD).

Drug interactions:

Antiarrhythmic agents of class I (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainid, propafenon) while the use of bisoprololum can reduce AV conduction and myocardial contractility. Antiarrhythmic agents of class III (e.g. amiodarone) may increase the violation of AV conduction. Effect of beta-blockers for topical application (e.g. eye drops for glaucoma treatment) may exacerbate the systemic effects of bisoprolol (decrease in blood pressure, slowing the heart rate).

Parasympathomimetic while the use of bisoprolol may increase the violation of AV conduction and increase the risk of bradycardia.

Coadministration of the drug with the Biological beta-agonists (e.g. isoprenaline, dobutamine) may cause decreased effect of both drugs. Combination of bisoprolol with agonists affecting beta - and alpha-adrenoceptors (e.g. norepinephrine, epinephrine), may potentiate the vasoconstrictor effects of these means that occur with the participation of alpha-adrenergic receptors, leading to increased blood pressure. Such interaction is more likely with use of nonselective beta-blockers.

Mefloquine while the use of bisoprololum can increase the risk of bradycardia.

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 diagnostic agents for/in the introduction increases the risk of anaphylactic reactions.

Phenytoin in the on/in the introduction, means for inhalation anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive actions and reduce the likelihood of AD. The effectiveness of insulin and hypoglycemic agents for oral administration may vary in the treatment of bisoprololum (masks the symptoms of developing hypoglycemia: tachycardia, the AD).

The clearance of lidocaine and xantinov (except theophylline) may be reduced in connection with a possible increase in their concentration in blood plasma, especially in patients with initially increased clearance of theophylline under the influence of Smoking. Weaken hypotensive effect of NSAIDs (delay of sodium ions and blockade of PG synthesis by the kidney), corticosteroids and estrogens (delays sodium ions).

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

Nifedipine can lead to significant reduction of HELL.

Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs can lead to excessive reduction of HELL. Effects of non-depolarizing muscle relaxants and anticoagulant effect of coumarins during treatment with bisoprolol can be extended.

Tricyclic and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedatives and hypnotics drugs increase oppression CNS.

Not recommended simultaneous application with MAO inhibitors because of significant increase gipotenzivnogo actions. The break in treatment between receiving MAO inhibitors and bisoprolol must be not less than 14 days.

Non-hydrogenated ergot alkaloids , including ergotamine, increase the risk of peripheral circulatory disorders.

Sulfasalazine bisoprolol improves concentration in plasma.

Rifampicin shortens T1/2 of bisoprolol.

Method of application and dose:

Inside, in the morning, on an empty stomach (before Breakfast), during Breakfast or after 1 times per day with a small amount of liquid. Tablets should not be chewed or crushed.

In all cases the mode of reception and dose selects the physician for each patient individually, taking into account in particular the variation and condition of the patient.

Arterial hypertension and ischemic heart disease

In arterial hypertension and ischemic heart disease Biological drug used for 5 mg 1 time per day. If necessary, increase the dose to 10 mg 1 time per day.

In the treatment of hypertension and angina maximum daily dose is 20 mg 1 time/day.

CHF

Initiating treatment of CHF drug Byol require a special titration phase and regular medical monitoring.

A prerequisite for drug treatment Byol CHF is stable without signs of deterioration.

The treatment of chronic heart failure drug Byol starts in accordance with the following scheme of titration. This may require individual adaptation, depending on how well the patient takes the prescribed dose, i.e. the dose can be increased only if the previous dose was well tolerated.

To ensure appropriate titration in 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 tabl. 5 mg) 1 times a day. Depending on individual tolerance dose can be increased to 2.5 mg (1/2 table. drug Byol 5 mg), 3.75 mg (3/4 tab. 5 mg), 5 mg (1 table. drug Byol 5 mg or 1/2 tab. 10 mg), 7.5 mg (3/4 tab. 10 mg) and 10 mg of 1 times a day at intervals of not less than 2 weeks.

If the increase in dose is poorly tolerated by the patient, may reduce the dose.

The maximum daily dose in the treatment of CHF is 10 mg 1 time per day.

During a titration it is recommended that regular monitoring of blood pressure, heart rate and symptoms of increasing severity of CHF. The worsening of CHF symptoms possibly from the first day of treatment.

During the titration phase or after it may cause temporary worsening of CHF, hypotension or bradycardia. In this case it is recommended first of all to pay attention to the selection of doses of concomitant standard therapy. You may also need a temporary reduction of the dose Byol 5 mg or cancel treatment. After stabilization of the patient's state should re-titration of the dose or continue the treatment.

Violation of the kidney or liver

The liver or kidney disease mild or moderate degree usually does not require dose adjustment. When expressed violations kidney function (Cl creatinine less than 20 ml/min) and in patients with severe liver disease the maximum dose is 10 mg. increasing the dose in these patients should be performed with extreme caution.

Elderly patients

Dose adjustment is not required.

To date, insufficient data regarding the use of the drug Byol 5 mg in patients with CHF associated with diabetes mellitus type 1, severe disorders of the kidney and/or liver disease, restrictive cardiomyopathy, congenital heart disease or hemodynamically due to a heart defect. Also still not received sufficient information regarding patients with CHF with myocardial infarction within the last 3 months.

Overdose:

Symptoms: arrhythmia, ventricular arrythmia, expressed aetiology, AV blockade, expressed lower AD, acute heart failure, hypoglycemia, acrocyanosis, shortness of breath, bronchospasm, dizziness, fainting, seizures.

Treatment: in the event of overdose, you should stop taking the drug, gastric lavage should be taken adsorbing means, spend symptomatic therapy.

At the expressed bradycardia — in/in the introduction of atropine. If the effect is insufficient, with care it is possible to introduce a means of having a positive chronotropic effect. Sometimes you may need a temporary production of an artificial pacemaker.

When expressed lower AD — in/in the introduction of plasma-substituting solutions and vasopressors. When hypoglycemia can be shown in/with the introduction of glucagon or dextrose (glucose). AV blockade — the patients should be under the supervision and to the treatment of &beta-agonists such as epinephrine. In case of need — the production of an artificial pacemaker.

If worsening of CHF in/with the introduction of diuretics, drugs with positive inotropic effect, as well as vasodilators.

With bronchospasm — appointment of bronchodilators, including &,beta-agonists and/or aminophylline.

Special instructions:

Should not abruptly discontinue treatment with Biological because of the risk of developing severe arrhythmias and myocardial infarction. Lifting a gradually reducing the dose by 25% every 3-4 days.

Status monitoring of patients taking the drug is Biological, should include measurement of HR and AD (at the beginning of treatment — daily, then 1 once in 3-4 mo), the ECG, determination of the concentration 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).

It should teach the patient methods of calculating heart rate and instruct on the need of medical advice if heart rate less than 50 beats/min.

In the case of elderly patients increasing bradycardia (heart rate less than 50 beats/min), expressed lower AD (sad less than 100 mm Hg.St.), AV blockade, it is necessary to reduce the dose or stop the treatment. Before treatment is recommended study of respiratory function in patients with severe bronchopulmonary history.

Patients using contact lenses should take into account that treatment with the drug may decrease the production of tear fluid.

If the drug Biological for patients with pheochromocytoma has the risk of paradoxical hypertension (if not previously achieved by effective blockade of alpha-adrenergic receptors).

In hyperthyroidism bisoprolol may mask certain clinical signs of hyperthyroidism (e.g. tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because it can enhance symptoms. At diabetes can mask the tachycardia, caused by hypoglycemia. Unlike nonselective beta-blockers, virtually no increases caused by insulin hypoglycemia and not delay restoration of the concentration of glucose in the blood to normal values. With simultaneous use of clonidine its reception can be terminated only a few days after discontinuation of the drug Byol.

Perhaps the increased severity of hypersensitivity reactions and lack of effect of conventional doses of epinephrine with aggravated allergic anamnesis.

If necessary for a planned surgical treatment, the drug should be discontinued for 48 h before General anesthesia. If the patient has taken the drug before surgery, he should choose drugs for General anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate/atropine (1-2 mg). Drugs that Deplete the depot 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 lower HELL or bradycardia.

Patients with bronchospastic diseases can carefully prescribed cardioselective beta-blockers in case of intolerance and/or ineffectiveness of other antihypertensive agents. In patients receiving beta-blockers in patients with concomitant bronchial asthma may increase airway resistance. When the dose of the drug Byol in these patients there is a risk of bronchospasm.

In case of detection of patients increasing bradycardia (heart rate less than 50 beats/min), expressed lower AD (sad less than 100 mm Hg.St.), AV blockade, it is necessary to reduce the dose or stop the treatment.

It is recommended to stop therapy with Byol in the development of depression.

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. The abolition of the drug are gradually, reducing the dose for 2 weeks or more (reduce the dose 25% in 3-4 day).

It should stop the drug before the study of concentration in blood and urine catecholamines, normetanephrine, vanillylmandelic acid, titles of antinuclear antibodies. In smokers the effectiveness of beta-adrenoblokatorov below.

Effects on ability to drive vehicles and perform other activities that require concentration and speed of psychomotor reactions. During the period of drug treatment Byol caution when driving and performing other potentially hazardous activities, require high concentration and psychomotor speed reactions.