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

Excipients: cellulose microcrystalline 44,500 mg / 62,400 mg, ludypress LCEE (lactose monohydrate 94.7-98.3%, povidone 3-4%) 40,000 mg / 38,500 mg, starch corn 8,000 mg / 11,000 mg, silicon dioxide colloid (aerosil) 0.500 mg / 0,600 mg, crospovidone (kollidone CL) 1,000 mg / 1,250 mg, magnesium stearate 1.00 mg / 1.250 mg;

shell: titanium dioxide 0.287 mg / 0.430 mg, macrogol (polyethylene glycol 4000) 0,287 mg / 0,430 mg, hypromellose 1,320 mg / 1,968 mg, talc 0,106 mg / 0,172 mg.

Description:

Round, biconvex tablets, covered with a film coating of yellow (for dosages of 5 mg) or dark yellow (for a dosage of 10 mg) colors. On the cross-section, two layers are visible, the inner layer is white or white with a barely noticeable creamy hue of color.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

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

Blocking in low doses 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 action, reduces atrioventricular (AV) conductivity and excitability. If the therapeutic dose is exceeded, beta₂-adrenoblocking action. The total peripheral vascular resistance at the beginning of the drug (in the first 24 hours) increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), which returns to the initial one after 1-3 days, and decreases with long-term administration.

Antihypertensive action is associated with a decrease in the minute volume of 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 activity 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 caused by a decrease in myocardial oxygen demand as a result ofreduction of heart rate and decrease in myocardial contractility, diastole lengthening, improvement of myocardial perfusion. By increasing the end-diastolic pressure in the left ventricle and increasing the stretching of the ventricular fibers, myocardial oxygen demand may increase, 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.

When used in average therapeutic doses, in contrast to non-selective beta blockers, 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. Absorption - 80-90%, food intake does not affect the absorption of the drug. The maximum concentration in the blood plasma is observed after 1-3 hours. Bioavailability is about 90%. The connection with blood plasma proteins is about 30%.

Distribution. The volume of distribution is 3.5 l / kg. Permeability through blood-brain and placental barriers is low.

Metabolism. Metabolised in the liver with the participation of isoenzymes CYP3A4 (up to 95%) and CYP2D6. The effect of "primary transmission" through the liver is insignificant (about 10%). Biotransformation of bisoprolol is not accelerated in patients with hyperthyroidism.

Excretion. The total ground clearance is 15.6 ± 3.2 l / h, the renal clearance is 9.6 ± 1.6 l / h. Balanced clearance of bisoprolol is determined by the balance between excretion through the kidneys in an unchanged form (about 50%) and oxidation 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 half-life is 9-12 hours.

The dependence of the pharmacokinetics of bisoprolol on the dose is linear. The pharmacokinetics of bisoprolol is stable, it does not depend on the age and sex of the patient.

Pharmacokinetics in special clinical cases

Renal insufficiency. In the case of severe renal dysfunction (clearance, creatinine less than 20 ml / min) and in patients with anuria, the half-life can increase more than 2-fold.

Liver failure. In the case of severe hepatic insufficiency, there is an increase in the half-life period to 13-15 hours.

Chronic heart failure. In patients with chronic heart failure (NYHA class III functional class), the concentration of bisoprolol in the blood plasma is higher than in healthy volunteers, and the elimination half-life is increased to 17 hours.

Indications:

- Arterial hypertension;

- andShestic heart disease: prevention of attacks of stable angina.

Contraindications:

Hypersensitivity to bisoprolol, other components of the drug and other beta-blockers; shock (including cardiogenic); pulmonary edema; acute heart failure or CHF in the stage of decompensation, requiring inotropic therapy; AV blockade II-III degree, without pacemaker; sinoatrial blockade; syndrome of weakness of the sinus node; bradycardia (heart rate less than 60 beats per minute);angina of Prinzmetal; cardiomegaly (no signs of heart failure); severe arterial hypotension (systolic blood pressure less than 100 mm Hg), especially with myocardial infarction; severe bronchial asthma and chronic obstructive pulmonary disease (COPD) in history; simultaneous administration of floktaphenin, sultopride, monoamine oxidase inhibitors (MAO), except for MAO type B; simultaneous intravenous administration of verapamil or diltiazem; severe violations of peripheral circulation, Raynaud's syndrome; pheochromocytoma (without simultaneous use of alpha-blockers); metabolic acidosis; age to 18 years (efficacy and safety not established).

Lactase deficiency, lactose intolerance, lactose malabsorption / isomaltose syndrome (the composition of the drug includes lactose).

Carefully:

Severe hepatic insufficiency, marked renal failure (creatinine clearance less than 20 ml / min), myasthenia gravis, thyrotoxicosis, diabetes mellitus (can mask symptoms of hypoglycemia), weighed allergic anamnesis, AV blockade of I degree, depression (including in the anamnesis), psoriasis, bronchial asthma, COPD, peripheral circulatory disorders, strict diet.

Pregnancy and lactation:

Bisoprolol does not have direct cytotoxic, mutagenic and teratogenic effects, but it has pharmacological effects that can have harmful effects on the course of pregnancy and / or on the fetus or newborn.

Usually beta-adrenoblockers reduce placental perfusion, which leads to a slowing of fetal growth, fetal death, miscarriage or premature birth. The fetus and newborn child may experience pathological reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.

Biprol should not be used during pregnancy. The use is possible if the benefit to the mother exceeds the risk of side effects in the fetus and / or the child. In the case when treatment with Biprol is considered necessary, blood flow in the placenta and uterus should be monitored, as well as the growth and development of the fetus. In case of appearance of undesirable phenomena in relation to pregnancy and / or fetus, alternative therapies should be used.

You should carefully examine the newborn after delivery.Symptoms of hypoglycemia and bradycardia arise, as a rule, during the first 3 days of life.

There is no data on the penetration of bisoprolol into breast milk, so taking Biprol is not recommended for women during lactation.

If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Biprol preparation is taken orally, in the morning, once a day with a small amount of liquid, before breakfast, during or after it. Tablets should not be chewed or ground into a powder. In all cases, the regimen and dosage are selected by the doctor for each patient individually, in particular, taking into account the heart rate and the patient's condition.

With arterial hypertension and ischemic heart diseasea the drug is prescribed 5 mg once a day. If necessary, increase the dose to 10 mg once a day.

In the treatment of hypertension and angina pectoris the maximum daily dose is 20 mg once a day.

For patients with severe renal dysfunction (creatinine clearance less than 20 ml / min) or with a marked impairment of liver function the maximum daily dose is 10 mg once a day. Increasing the dose in such patients should be done with extreme caution.

Patients old age correction of the dose is not required.

Side effects:

The frequency of the side effects listed below is indicated in accordance with the WHO classification: very 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%; very rarely - less than 0.01%, including individual cases.

From the central and peripheral nervous system: often - increased fatigue, asthenia, dizziness, headache. Usually, these phenomena develop at the beginning of treatment, as a rule, are slightly expressed and take place within 1-2 weeks; infrequently - sleep disorders, depression; rarely - nightmares, hallucinations, loss of consciousness.

From the side of the cardiovascular system: very often bradycardia, palpitation; often a marked decrease in blood pressure (especially in patients with CHF), manifestations of angiospasm (increased peripheral circulation disorders, cold sensation in the extremities (paresthesia), infrequent AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias,aggravation of the course of CHF with the development of peripheral edema (swelling of the ankles, feet) and dyspnea, orthostatic hypotension, chest pain.

From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain, constipation, dryness of the oral mucosa; rarely - hepatitis, increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase), increased bilirubin concentration.

From the respiratory system: infrequently - laryngo- and bronchospasm in patients with bronchial asthma or obstructive airways disease; rarely - allergic rhinitis, nasal congestion.

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

From the sense organs: rarely - visual impairment, reduced tearing (should be taken into account when wearing contact lenses), hearing impairment, taste change; very rarely - dryness and soreness of the eyes, conjunctivitis.

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

From the endocrine system: rarely - hypoglycemia.

From the genitourinary system: rarely - a violation of potency, a weakening of the libido.

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 flushing, itching, skin rash, urticaria.

Laboratory indicators: rarely - hypertriglyceridemia; very rarely - thrombocytopenia, agranulocytosis, leukopenia.

Other: rarely - withdrawal syndrome (increased angina attacks, increased blood pressure).

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.

Treatment: gastric lavage, the appointment of absorbents, symptomatic therapy.

With severe bradycardia - intravenous atropine. If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect.Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With developed AV blockade - intravenous administration 1-2 mg atropine, epinephrine or setting a temporary pacemaker.

With ventricular extrasystole - lidocaine (preparations IA class do not apply).

With a marked reduction in blood pressure, the patient should be moved to the Trendelenburg position; if no signs of pulmonary edema - intravenous plasma-substituting solutions in their inefficiency - administration of epinephrine, dopamine, dobutamine (to maintain chronotropic and inotropic action and eliminate expressed lowering blood pressure).

In hypoglycemia, intravenous administration of a dextrose solution (glucose) can be indicated.

With heart failure - cardiac glycosides, diuretics.

With convulsions - intravenously diazepam.

With bronchospasm - inhalation beta₂- adrenomimetics.

Interaction:

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 (joint use is contraindicated).

MAO inhibitors. It is not recommended simultaneous use (with the exception of MAO type B), 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.

Blocks of "slow" calcium channels (diltiazem and verapamil). This combo should be avoidedination. During the period of treatment with Biprol, intravenous administration of verapamil or diltiazem and other antiarrhythmic drugs is contraindicated. Due to the synergism of the action, a sharp drop in blood pressure, a violation of automatism (pronounced bradycardia, stopping the sinus node), violations AV conduction, heart failure). If this combination is necessary, careful clinical and electrocardiographic monitoring of patients, especially the elderly and at the beginning of treatment, is required.

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) with simultaneous application possible decrease AV conduction and contractility of the myocardium (combination with bisoprolol should be avoided).

Antiarrhythmic drugs of III class (eg, amiodarone). When combined with bisoprolol, breach of contractility, automatism and conduction due to suppression of sympathetic compensatory mechanisms is possible (this combination should be avoided).

Antihypertensive agents of central action (clonidine, apraclonidine; alpha-methyldopa, guanfacine, moxonidine, rilmenidine). When combined, an increased risk of developing severe bradycardia, stopping the sinus node, AV conduction, a sharp decrease in blood pressure, heart failure (synergistic effect). This combination should be avoided. If necessary, careful clinical and electrocardiographic monitoring is required, especially in elderly patients and at the beginning of treatment: Significant increase in blood pressure with a sharp reversal of the antihypertensive drug of central action.

Cardiac glycosides. Reduction of heart rate, conduction disturbance.

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).

Calcium channel blockers (eg, nifedipine). There may be an excessive decrease in blood pressure.

Parasympathomimetics. When combined, the risk of developing bradycardia.

Meflohin. Joint application with bisoprolol increases the risk of developing bradycardia (additive effect).

Phenytoin with intravenous administration, drugs for inhalation of general anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of lowering blood pressure. Simultaneous application with beta-adrenomimetics (e.g., isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

The combination of bisoprolol from adrenomimetics, affecting beta and alpha-adrenergic receptors (eg, norepinephrine, epinephrine), can enhance the vasoconstrictive effect of these agents, which occurs with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure.Such interactions are more likely when using nonselective beta-blockers.

Bisoprolol can change the effectiveness of insulin and hypoglycemic agents for oral administration, mask the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Bisoprolol reduces clearance lidocaine and xanthineat (except diphylline) and increases their concentration in the plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Antihypertensive effect weaken nonsteroidal anti-inflammatory drugs (delay of sodium ions and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion retention).

Diuretics, sympatholytics, hydralazine and other hypotensive medicines. Risk of excessive lowering of blood pressure.

Bisoprolol lengthens the action Nondepolarizing muscle relaxants and anticoagulant effect coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics medicines - when combined with bisoprolol, an intensification of central nervous system depression.

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

Ergotamine increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in plasma.

Rifampicin reduces the half-life of bisoprolol.

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 tools for intravenous administration increase the risk of developing anaphylactic reactions.

Special instructions:

Treatment with the drug is usually long-term.

Before the start of treatment, it is recommended that a study of the function of external respiration be performed in patients with a history of bronchopulmonary anamnesis. Patients with bronchospastic diseases can be prescribed bisoprolol in case of intolerance and / or inefficiency of other antihypertensive drugs,while strictly following the dose of the drug. Overdosing is dangerous by the development of bronchospasm.

Monitoring of patients receiving bisoprolol, should include monitoring the heart rate, blood pressure (at the beginning of treatment - every day, then once in 3-4 months), electrocardiograms, plasma glucose concentrations in patients with diabetes (1 time in 4-5 months). In elderly patients it is recommended to monitor kidney function (1 time in 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.

Approximately in 20% of patients with angina pectoris beta-blockers are ineffective. The main causes are severe coronary atherosclerosis with a low threshold of ischemia (heart rate less than 100 beats / min) and an increase in the end diastolic volume of the left ventricle, which disrupts the subendocardial blood flow.

In "smokers" the effectiveness of beta-blockers is lower.

Patients who use contact lenses should take into account that a reduction in tear fluid production is possible against the background of treatment.

When used in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless an effective alpha-adrenoblockade has been previously achieved).

With thyrotoxicosis bisoprolol can mask certain clinical signs of thyrotoxicosis (eg, tachycardia). Sharp abolition in patients with thyrotoxicosis is contraindicated, as it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it does not actually increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

With the simultaneous use of clonidine, its administration can be stopped only a few days after the withdrawal of bisoprolol.

It is possible to increase the severity of the reaction of hypersensitivity and the lack of effect from the usual doses of epinephrine against the background of a burdened allergological anamnesis.

In case of necessity of carrying out of planned surgical intervention, the drug is withdrawn 48 hours before the start of general anesthesia.If the patient has taken the drug before surgery, he should choose a medicine for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Drugs that reduce catecholamine stores (for example, reserpine), can enhance the action of beta-blockers, so patients taking such a combination of drugs should be under constant observation of the doctor for the detection of arterial hypotension or bradycardia.

In the case of elderly patients with increasing bradycardia (less than 60 beats per minute), 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.

Bisoprolol treatment should not be discontinued abruptly because of the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose for 2 weeks or more (dose reduced by 25% in 3-4 days).

It is recommended to stop therapy (with a gradual decrease in dose) with the development of depression caused by taking the drug.

The drug should be discontinued before the study of the blood and urine content of catecholamines, normetanefrin and vanillin-mandelic acid, the titer of antinuclear antibodies.

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

During the treatment period, care must be taken when driving vehicles and performing other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 5 mg and 10 mg.

Packaging:

For 10 tablets in a planar cell pack of polyvinylchloride film and aluminum foil.

For 3, 5 or 10 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place, 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:LS-001581

Date of registration:15.09.2011 / 08.12.2015

Expiration Date:Unlimited

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

HEMOFARM, LLC Russia

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Biprol (Biprol)