Biprol - instructions for use, doses, side effects, contraindications

Excipients: cellulose microcrystalline 40.00 mg, ludypress LCEE (lactose monohydrate 94.7-98.3%, povidone 3-4%) 38.05 mg, corn starch 7.20 mg, silicon dioxide colloid (aerosil) 0.45 mg, crospovidone 0.90 mg, magnesium stearate 0.90 mg;

film sheath: titanium dioxide 0.43 mg, macrogol (polyethylene glycol 4000) 0.20 mg, hypromellose (hydroxypropylmethylcellulose) 1.27 mg, talc 0.10 mg.

Description:

Round, biconvex tablets, covered with a film coat of white color, with a risk. On the fracture, the core is white or almost white.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Selective beta₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. Has antihypertensive, antiarrhythmic and anti-anginal action.

Blocking in low doses of beta₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate from adenosine triphosphate, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect, reduces atrioventricular (AV) conductivity and excitability.Has only a slight affinity for beta₂-adrenoreceptors of smooth muscles of bronchi and vessels, and also to beta₂adrenoreceptors involved in the regulation of metabolism. therefore bisoprolol in general, does not affect the resistance of the respiratory tract and the metabolic processes in which beta is involved₂adrenoreceptor. If the therapeutic dose is exceeded, beta₂-adrenoblocking action. The total peripheral vascular resistance, which at the beginning of application (in the first 24 hours) increases somewhat (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), after 1-3 days it returns to the initial, and with prolonged use decreases.

Antihypertensive action is associated with a decrease in the minute volume of the blood, sympathetic stimulation of the peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (important for patients with initial renin hypersecretion), restoration of the sensitivity of the aortic baroreceptors (there is no increase in their activation in response to a decrease in blood pressure) and influence on the central nervous system.With arterial hypertension, the effect develops in 2-5 days, stable effect - after 1-2 months.

Antianginal action is caused by a decrease in myocardial oxygen demand as a result of a decrease in the heart rate and a decrease in myocardial contractility, diastole lengthening, and improvement in myocardial perfusion. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers, the ventricles can increase the need for oxygen at the beginning of the treatment, especially in patients with chronic heart failure (CHF).

Antiarrhythmic action is caused by elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of cyclic adenosine monophosphate, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing AV conducting (mainly in antegrade and, to a lesser extent, in retrograde directions) through the atrioventricular node and along additional routes.

With chronic heart failure bisoprolol reduces the severity of activation of the sympathoadrenal and renin-angiotensin-aldosterone system, which helps prevent the progression of the disease, improve the prognosis and reduce the number of hospitalizations.

Bisoprolol, in contrast to nonselective beta-blockers, when used in moderate therapeutic doses, has a less pronounced effect on organs containing beta₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; does not cause retention of sodium ions in the body.

Pharmacokinetics:

Suction. Bisoprolol almost completely (more than 90%) is absorbed from the gastrointestinal tract. Bioavailability after oral administration is up to 90% (due to a minor metabolism "during the primary passage" through the liver). Eating does not affect bioavailability. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution. The connection with plasma proteins is about 30%, which reduces the likelihood of interaction with other drugs that bind to proteins. Bisoprolol is distributed rather widely, the volume of distribution is 3.5 l / kg. Permeability through blood-brain and placental barriers is low.

Metabolism. Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are water soluble and excreted by the kidneys. The main metabolites found in blood plasma and urine are pharmacologically inactive. In studies with microsomes of human liver in vitro determined that bisoprolol is metabolized mainly with the help of the CYP3A4 isoenzyme (up to 95%) and, to an insignificant degree, the isoenzyme CYP2D6. Biotransformation of bisoprolol is not accelerated in patients with hyperthyroidism.

Excretion. Bisoprolol clearance is determined by the balance between excretion by the kidneys (50%) in unchanged form and metabolism in the liver (about 50%) to inactive metabolites, which are then excreted by the kidneys; less than 2% is excreted through the intestine (with bile). Does not accumulate in the body. The elimination half-life is 9-12 hours (which allows bisoprolol 1 time per day). The total clearance of bisoprolol is 15.6 ± 3.2 l / h, the renal clearance is 9.6 l / h.

Linearity. The dependence of the pharmacokinetics of bisoprolol on the dose is linear.

Pharmacokinetics of bisoprolol in special clinical cases

The pharmacokinetics of bisoprolol is stable, independent from the patient's age and sex.

In patients with CHF (III functional class by classification NYHA) the concentration of bisoprolol in the blood plasma is higher than that of healthy volunteers, and the half-life is increased to 17 hours.

Renal failure. In the case of severe renal dysfunction (creatinine clearance less than 20 ml / min) and in patients with anuria, the half-life of bisoprolol may increase by a factor of 2.

Liver failure. In severe hepatic failure, the half-life is prolonged to 13-15 hours.

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous impairment of liver or kidney function.

Indications:

Chronic heart failure.

Contraindications:

- Hypersensitivity to bisoprolol, other beta-blockers or any of the excipients of the drug (see section "Composition");

- acute heart failure or chronic heart failure in the stage of decompensation, requiring intravenous administration of drugs with a positive inotropic effect;

- shock (including cardiogenic);

- atrioventricular blockade II or III degree (without pacemaker);

- syndrome of weakness of the sinus node;

- sinoatrial blockade;

- pronounced bradycardia (heart rate less than 60 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 100 mm pt. st.), especially with myocardial infarction;

- severe bronchial asthma, chronic obstructive pulmonary disease in history;

- expressed by peripheral circulatory disorders or severe forms of Raynaud's syndrome;

- pheochromocytoma (without simultaneous use of alpha-blockers);

- metabolic acidosis;

- concurrent use of monoamine oxidase inhibitors (MAO) (except MAO-B inhibitors), floctafenine, sultopride;

- simultaneous intravenous administration of verapamil or diltiazem;

- lactase deficiency, lactose intolerance, malabsorption syndrome (the formulation includes lactose monohydrate);

- age to 18 years (due to insufficient data on effectiveness and safety of use).

Carefully:

- severe renal impairment (creatinine clearance less than 20 mL / min);

severe hepatic impairment;

- restrictive cardiomyopathy;

- Congenital heart defect;

- Valvular heart valve with severe hemodynamic disorders;

- a history of myocardial infarction within the last 3 months;

- AV blockade of the 1st degree;

- Prinzmetal angina;

- violations of peripheral circulation;

- Type 1 diabetes mellitus or diabetes mellitus with significant fluctuations in the concentration of glucose in the blood;

- bronchial asthma, chronic obstructive pulmonary disease;

- Myasthenia gravis;

- thyrotoxicosis;

- pheochromocytoma (with simultaneous use of alpha blockers);

- Depression (including in the anamnesis);

- psoriasis;

- Weighed allergic anamnesis, the period of desensitizing therapy;

- a strict diet (see section "Special instructions").

Pregnancy and lactation:

Pregnancy. Bisoprolol does not have direct cytotoxic, mutagenic and teratogenic effects, but it has pharmacological effects that can have a negative effect on the course of pregnancy and / or the fetus or the newborn. Usually beta-adrenoblockers reduce placental perfusion, which can lead to a slowing of fetal growth, fetal death, miscarriage or premature birth.Such a pathological reaction as hypoglycaemia, bradycardia, respiratory depression can occur in a fetus and a newborn baby.

Biprol should not be used during pregnancy, except when the benefit to the mother exceeds the risk of side effects in the fetus and / or the child. When treatment with Biprol is considered necessary, blood flow in the placenta and uterus should be monitored, and fetal growth and development monitored, and alternative therapies should be applied if pregnancy and / or fetus are undesirable. Care should be taken to examine the newborn after delivery; symptoms of hypoglycemia and bradycardia occur, usually during the first 3 days of life.

Lactation. There is no data on the isolation of bisoprolol in breast milk, therefore, taking Biprol during breastfeeding is not recommended. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, with a small amount of liquid, once a day in the morning (before breakfast, during or after it).Tablets should not be chewed or ground into a powder.

Preliminary conditions for starting treatment with Biprol are stable chronic heart failure without signs of exacerbation for six weeks; treatment with optimal doses of standard CHF therapy; no changes in standard therapy of CHF in the previous two weeks.

Beginning of treatment with Biprol requires mandatory carrying out of a special phase of titration and regular medical supervision.

The titration phase

The recommended initial dose of Biprol is 1.25 mg (¹/₂tablets of 2.5 mg) once a day. Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg once daily. Each subsequent increase in dose should be carried out at intervals of not less than 2 weeks. If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible. The maximum recommended (target) dose of Biprol in chronic heart failure is 10 mg once a day.

During the titration phase, regular monitoring of the heart rate, blood pressure and signs of worsening of the course of chronic heart failure,which can develop from the first day of application of the drug.

After taking the initial dose of 1.25 mg (¹/₂2.5 mg tablets) should be observed for 4 hours (control of heart rate, blood pressure, conduction disorders, signs of worsening of heart failure); if necessary, the drug is canceled.

Each dose increase should be carried out only if the previous dose is well tolerated and the patient is stable. With dubious tolerability and excessive lowering of blood pressure, the dose is increased 1 time in 4 weeks; with a target dose can be reached by the 24th week. If it is not possible to reach the target dose, the patient should receive the maximum tolerated dose.

During the period of titration or maintenance therapy, temporary deterioration of the course of heart failure, arterial hypotension or bradycardia can be observed. In these cases, it is recommended to first adjust the dosage of concomitant medications (a diuretic and / or an angiotensin converting enzyme (ACE) inhibitor, if this measure is ineffective, a temporary decrease, a slower titration of the dose, or cancellation of the Biprol preparation may be required.Renewal of therapy and / or titration of the dose of Biprol should be considered only after stabilization of the patient's condition.

You should not allow a sudden discontinuation of the Biprol preparation (as well as any beta-blocker), as the development of the "cancellation" syndrome, which is manifested by signs of CHF decompensation, is possible. Therefore, the cancellation and reduction of the dose of Biprol should be carried out gradually, under the supervision of the doctor, taking into account the individual reactions of the patient (see section "Special instructions").

If you miss a dose of the next dose, you should not double the next dose.

Duration of treatment

The drug Biprol is usually prescribed for long-term therapy, the duration of which is determined by the doctor.

Special patient groups

Patients with impaired renal or hepatic function. If there is a mild or moderate degree of kidney or liver dysfunction, dose adjustment is not required. In case of severe impairment of renal function (creatinine clearance less than 20 ml / min) and in patients with severe liver diseases, titration of the dose is carried out with extreme caution (see section "With caution"); the maximum daily dose of Biprol is 10 mg.

Patients of advanced age. Correction of the dose is not required.

Children. In connection with the lack of data, the use of Biprol in children under 18 is not recommended.

Patients with concomitant diseases. Currently, there is insufficient data on the use of bisoprolol in patients with CHF in combination with type 1 diabetes mellitus, severe renal and / or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve defects with severe hemodynamic disorders, myocardial infarction during the last 3 months (see "With caution").

Side effects:

The frequency of the side effects listed below is indicated in accordance with the classification World Health Organization: Often - more than 10%; often - more than 1% and less than 10%; infrequently - more than 0,1% and less than 1%; rarely - more than 0,01% and less than 0,1%; rarely - less than 0.01%, including individual cases.

From the side of the cardiovascular system: Often - a bradycardia, sensation of palpitation; often - marked decrease in blood pressure, worsening of CHF with development of peripheral edema (swelling of the ankles, feet) and shortness of breath, sensation of cold or numbness in the extremities (paresthesia); infrequently - violation of AV conduction (up to complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, chest pain.

From the central and peripheral nervous system: often - dizziness, headache, asthenia, increased fatigue; infrequently - depression, insomnia; rarely - hallucinations, nightmares.

Usually, these phenomena develop at the beginning of the course of treatment, usually expressed slightly and pass within 1-2 weeks after the start of treatment.

From the respiratory system: infrequently - Laryngo- and bronchospasm in patients with bronchial asthma or obstructive airway disease in history; rarely - Allergic rhinitis, nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain, constipation, a feeling of dryness of the oral mucosa; rarely - Hepatitis.

From the musculoskeletal system: infrequently - muscle weakness, cramps in the calf muscles, arthralgia.

From the organon of feelings: rarely - impaired vision, reduced tearing (should be taken into account when wearing contact lenses), hearing impairment, change in taste; rarely - a feeling of dryness and soreness of the eyes, conjunctivitis.

From the skin: rarely - increased sweating, psoriasis-like skin reactions; rarely - Alopecia, exacerbation of psoriasis.

From the endocrine system: rarely - hypoglycemia.

From the side of the reproductive system: rarely - a violation of potency (the frequency does not differ from placebo).

From the immune system: rarely - the appearance of antinuclear antibodies with unusual clinical symptoms of lupus-like syndrome, which disappear after the end of treatment.

Allergic reactions: rarely - skin itching, rash, urticaria, skin hyperemia.

Laboratory indicators: rarely - Increase in the concentration in the blood plasma of triglycerides, increase in the activity of "hepatic" transaminases (aspartate aminotransferase, alanine aminotransferase), bilirubin; rarely - Thrombocytopenia, agranulocytosis, leukopenia.

Other: rarely - withdrawal syndrome.

Overdose:

Symptoms

Arrhythmia, ventricular extrasystole, pronounced bradycardia, AV blockade, marked decrease in blood pressure, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

The cases of bisoprolol overdose were single, bradycardia and / or a marked decrease in blood pressure were observed. The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients and, probably, patients with CHF are highly sensitive.

Treatment

In the event of an overdose, it is recommended, first of all, that bisoprolol can be canceled, gastric lavage, the appointment of adsorptive agents and maintenance and symptomatic therapy.

With severe bradycardia - intravenous administration of atropine (1-2 mg). If the effect is insufficient, with caution you can inject isoprenaline or another agent that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With developed AV blockade patients should be under constant supervision, receive treatment with beta-adrenomimetics, such as epinephrine (adrenalin); in case of need - the statement of the artificial driver of a rhythm.

With ventricular extrasystole - lidocaine (antiarrhythmic drugs of the IA class do not apply).

At the expressed depression of arterial pressure - the patient should be translated and Trendelenburg position; if there are no signs of pulmonary edema, intravenous administration of plasma-substituting solutions is indicated, with their inefficiency - the introduction of epinephrine (adrenaline), dopamine, dobutamine (to maintain chronotropic and lyotropic action and eliminate a pronounced decrease in blood pressure).

With hypoglycemia - intravenous administration of a solution of dextrose (glucose).

With exacerbation of CHF flow - intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

With bronchospasm - the appointment of bronchodilators, including beta₂adrenomimetics and / or aminophylline.

With cramps - intravenously diazepam.

Hemodialysis does not significantly increase the excretion of bisoprolol.

Interaction:

The effectiveness and tolerability of bisoprolol may be affected by other concomitant medications. Such interaction is also possible in the case when two drugs are taken in a short time. It is necessary to inform the doctor about other medications taken, even if they are taken without prescription (OTC drugs).

Floktaphenin. In case of shock or hypotension due floctafenine, beta-blockers cause reduction compensatory cardiovascular reactions (joint use is contraindicated).

Sulphoprid. Due to the additive effect, it is possible to develop a pronounced bradycardia; high risk of ventricular arrhythmias (joint use contraindicated).

MAO inhibitors. Joint use is not recommended (with the exception of MAO type B inhibitors), since the likelihood of significant enhancement of antihypertensive action is high. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Blockers of "slow" calcium channels: verapamil and, to a lesser extent, diltiazem. Due to the synergistic effect when combined with bisoprolol may slow down AV conductivity and a decrease in the contractility of the myocardium (this combination should be avoided).

During the treatment with Biprol, intravenous administration of verapamil or diltiazem and other antiarrhythmic drugs is contraindicated (the risk of developing asystole, AV blockade of high degree, severe bradycardia, severe arterial hypotension, increased heart failure).

Hypotensive means of central action (eg, clonidine, apraclonidine, alpha-methyldopa, moxonidine, rilmenidine). It is not recommended joint use with bisoprolol. Due to the synergism of the action and inhibition of sympathetic compensatory mechanisms, the risk of developing severe bradycardia, stopping the sinus node, AV conductivity, pronounced reduction in blood pressure, reduction in cardiac output. Abrupt cancellation, especially before bisoprolol cancellation, increases the risk of developing "ricochet" hypertension (see section "Special instructions").

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when combined with bisoprolol reduce AV conductivity and increase the negative inotropic effect (strict clinical and electrocardiographic observation is required).

Antiarrhythmics III class (eg, amiodarone). It is possible to increase the negative effect on AV conductivity.

Blocks of "slow" calcium channels - dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine). The risk of a marked decrease in blood pressure and increased heart failure is increased.

Parasympathomimetics. Possible increased violations AV conduction and an increased risk of bradycardia.

Beta-blockers for topical use (eg, eye drops for the treatment of glaucoma) can enhance the systemic action of bisoprolol (lowering blood pressure, decreasing heart rate).

Insulin and hypoglycemic agents for oral administration. When combined, it is possible to increase the hypoglycemic effect. Symptoms of hypoglycemia, in particular tachycardia, can be masked or suppressed. This interaction is more typical for non-selective beta-blockers.

Means for inhalation general anesthesia, derivatives of hydrocarbons (e.g., chloroform, cyclopropane, halothane, methoxyflurane) increase the severity of cardiodepressive action and the likelihood of arterial hypotension (see section "Special instructions").

Cardiac glycosides. Increased risk of bradycardia, lengthening of time AV carrying out.

Nonsteroidal anti-inflammatory drugs (due to delay of sodium ions and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (due to the delay of sodium ions) weaken the antihypertensive effect of bisoprolol.

Beta-adrenomimetics (e.g., isoprenaline, dobutamine). Possible weakening of both drugs.

Adrenomimetics, affecting beta and alpha-adrenergic receptors (eg, norepinephrine, epinephrine). It is possible to enhance the vasoconstrictor effects of these agents, which occur with the participation of alpha-adrenergic receptors, with an increase in blood pressure. Such interaction is more likely with nonselective beta-blockers.

Diuretics, sympatholytics, hydralazine, Other drugs with potential effect on blood pressure. When combined, there may be an excessive decrease in blood pressure.

Tricyclic and tetracyclic antidepressants, sedatives, hypnotics and antipsychotic medicines (antipsychotics), ethanol. When combined, it is possible to excessively reduce blood pressure and increase the inhibition of the central nervous system.

Meflokhin. Increased risk of bradycardia (additive effect).

Sympathomimetics, xanthines (aminophylline, theophylline). There may be a mutual weakening of therapeutic effects.

Baclofen. Increased risk of hypotension.

Unhydrated alkaloids of ergot, ergotamine increase the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens the half-life of bisoprolol (clinically insignificant).

Allergens used for immunotherapy, or extracts of allergens for skin tests can provoke severe systemic allergic reactions in patients receiving bisoprolol (see the "Caution" section).

Iodine-containing radiopaque diagnostic tools for intravenous administration increase the risk of developing anaphylactic reactions, refractory to treatment. Bisoprolol lengthens the action non-profitpandmuscle relaxants and anticoagulant effect coumarins.

Special instructions:

- At the initial stages of treatment Biprol patients need to be observed with control heart rate, blood pressure (at the beginning of treatment daily, then once every 3-4 months), electrocardiograms, plasma glucose concentrations in patients with diabetes mellitus (1 time in 4-5 months). In elderly patients, it is recommended that kidney function be monitored once every 4-5 months.

It is necessary to teach the patient how to calculate the heart rate and instruct him about the need for medical advice if it is less than 60 beats / min.

- Do not abruptly discontinue treatment with Biprol or change the recommended dose without first consulting a doctor, especially in patients with IHD (risk of developing severe arrhythmias, myocardial infarction, CHF decompensation). Abolition is carried out gradually (for 2 or more weeks), reducing the dose to ¹/₄ in 3-4 days.

- In patients with a history of bronchopulmonary anamnesis Before starting treatment, it is recommended to study the function of external respiration. In bronchial asthma or chronic obstructive pulmonary disease, the simultaneous administration of bronchodilating agents, the periodic monitoring of the clinical state and parameters of the function of external respiration are shown.In patients with bronchial asthma, an increase in airway resistance may be required, which will require a higher dose of beta₂-adrenomimetics. In "smokers" the effectiveness of beta-blockers is lower.

- In patients with a history of allergic anamnesis beta-blockers, including bisoprolol, can increase the sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the action of beta-adrenoblockers. In this case, the effect of the use of epinephrine (adrenaline) may be absent (see sections "With caution", "Interaction with other medicinal products").

- Have patients with diabetes mellitus bisoprolol can mask tachycardia caused by hypoglycemia (cm section "With caution", "Interaction with other drugs"), in contrast to non-selective beta-blockers, does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood plasma to normal levels.

- Patients with AV blockade I degree, disturbance of peripheral blood circulation of mild and moderate degree is possible to increase symptoms, exacerbation of the disease, especially at the beginning of treatment (see the section "With caution").

- Have patients with psoriasis, including in the history, beta-blockers (including bisoprolol) can be applied only by carefully weighing the ratio of the benefits of treatment and risk (see the section "With caution").

- If you need to cancel the drug Biprol before a planned surgical intervention, this should be done gradually and completed 48 hours before the start of general anesthesia. The patient who took the Biprol preparation before surgery should choose a drug for general anesthetics with minimal negative inotropic effect (see section "Interaction with other drugs"). Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

- In patients with pheochromocytoma the preparation Biprol can be appointed only at achievement of an effective alpha-adrenoblockade (risk of development of a paradoxical arterial hypertensia).

- With thyrotoxicosis The drug Biprol can mask the symptoms of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of bisoprolol in patients with thyrotoxicosis is contraindicated, since it can intensify the symptoms.

- With the simultaneous use of clonidine his reception can be stopped only a few days after the withdrawal of the drug Biprol.

- Patients taking Biprol in combination with drugs that reduce the supply of catecholamines (eg, reserpine), should be under the supervision of a doctor for the diagnosis of arterial hypotension or bradycardia. In case of development the patients, especially the elderly, an increasing bradycardia (less than 60 beats / min), arterial hypotension (systolic blood pressure below 100 mm Hg) AV blockade, bronchospasm, ventricular arrhythmias, severe impairment of liver and kidney function, it is necessary to reduce the dose or stop treatment with bisoprolol.

- It is recommended to stop therapy (gradually reducing the dose) with the development of depression, caused by taking Biprol, or before the study the content in the blood and urine of catecholamines, normetanephrine, vanillylmandelic acid,titer of antinuclear antibodies.

- During the treatment with Biprol, alcohol should be avoided.

- Patients who use contact lenses, should take into account that against the background of treatment, it is possible to reduce the production of tear fluid.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care should be taken when driving vehicles and performing other activities requiring increased concentration of attention and speed of psychomotor reactions. Due to individual reactions, the ability to drive vehicles and work with technically complex machinery can be compromised. This should be paid special attention at the beginning of treatment, after changing the dose, as well as in the case of simultaneous use of alcoholic beverages.

Form release / dosage:

Tablets, film-coated, 2.5 mg.

Packaging:

10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2, 3, 5 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a place protected from light and moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002832

Date of registration:22.01.2015 / 16.12.2015

Expiration Date:22.01.2020

The owner of the registration certificate:Nizhny Novgorod Chemical and Pharmaceutical Plant, OJSCNizhny Novgorod Chemical and Pharmaceutical Plant, OJSC

Manufacturer: & nbsp

MAKIZ-PHARMA, LLC Russia

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Biprol (Biprol)