Biprol, 5 mg 30 pcs.

A selective beta1-adrenoblocker with no sympathomimetic activity of its own, has no membrane stabilizing effect.

It has antihypertensive, antiarrhythmic and antianginal action.

By blocking in low doses beta1-adrenoreceptors of the heart it decreases stimulated by catecholamines formation of cyclic adenosine monophosphate from adenosine triphosphate, decreases intracellular ions flux.br>
calcium, has negative chrono-, dromo-, batmo- and inotropic effects, reduces atrioventricular (AV) conduction and excitability.

In case of therapeutic dose it has beta2-adrenoblocking action.

The total peripheral vascular resistance at the beginning of the drug administration (during the first 24 hours) increases (as a result of reciprocal increase of activity of alpha-adrenoreceptors and elimination of

stimulation of beta2-adrenoreceptors) that after 1-3 days returns to the initial level, and decreases after the long-term administration.

Antihypertensive effect is associated with reduction of the minute blood volume, sympathetic stimulation of peripheral vessels, reduction of renin-angiotensin-aldosterone system activity (of great importance for patients with

initial renin hypersecretion), restoration of sensitivity of aortic arch baroreceptors (there is no increase of their activity in response to a decrease in blood pressure) and the effect on the central nervous system.

In case of arterial hypertension the effect is developed in 2-5 days, its stable effect – in 1-2 months.

Antianginal action is determined by the decrease of myocardial oxygen demand due to slow heart rate and decreased myocardial contractility, prolongation of diastole, improvement of myocardial perfusion.

By increasing end diastolic pressure in the left ventricle and increasing ventricular muscle fiber stretch may increase myocardial oxygen demand, especially in patients with chronic heart failure (CHF).

Antiarrhythmic action is due to the elimination of arrhythmogenic factors (tachycardia, increased sympathetic nervous system activity, increased cyclic adenosine monophosphate,

arterial hypertension), decreased rate of spontaneous excitation of sinus and ectopic pacemakers, and deceleration of AV conduction (predominantly antegrade and, to a lesser extent, retrograde) through the atrioventricular node and along accessory pathways.

In contrast to non-selective beta-adrenoblockers, when administered in medium therapeutic doses it has less pronounced effect on organs containing beta2-adrenoreceptors (pancreas, skeletalbr>
muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism; does not cause sodium ion retention in the body.

Pharmacokinetics

Absorption. Absorption is 80-90%, food intake does not affect absorption of the drug. Maximal concentration in blood plasma is observed after 1-3 hours. Bioavailability is about 90%. Binding with blood plasma proteins is about 30%.

Distribution. Volume of distribution is 3.5 l/kg. Permeability through the blood-brain barrier and the placental barrier is low.

Metabolism. Metabolized in liver with participation of CYP3A4 (up to 95%) and CYP2D6 isoenzymes. The effect of “primary passage” through the liver is insignificant (about 10%). Biotransformation of bisoprolol is not accelerated in patients with thyroid hyperfunction.

Excretion. Total clearance is 15.6±3.2 l/hour, renal clearance is 9.6±1.6 l/hour. Balanced clearance of bisoprolol is determined by the balance between its excretion through the kidneys unchanged (about

50%) and oxidation in the liver (about 50%) to inactive metabolites, which are then also excreted by the kidneys; less than 2% is excreted through the intestine (with bile). It does not accumulate in the body. Half-life period is 9-12 hours.

Dependence of bisoprolol pharmacokinetics on dose is linear.

Pharmacokinetics of bisoprolol is stable, independent of patient age and sex.

Pharmacokinetics in special clinical cases

Renal insufficiency. In case of marked renal function impairment (creatinine clearance less than 20 ml/min) and in patients with anuria half-life period may increase more than 2 times.

Hepatic insufficiency. In case of severe hepatic insufficiency half-life period is increased up to 13-15 hours.

Chronic heart failure.

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

Indications

Tachycardia, Arrhythmia, Hypertension (high blood pressure), Heart palpitations, Cardialgia (pain in the heart), Heart failure

• Arterial hypertension.
• Ischemic heart disease: prevention of attacks of stable angina.

.

Active ingredient

Bisoprolol

Composition

Active ingredient

Bisoprolol fumarate 5,000 mg/10,000 mg;

Excipients:

Microcrystalline cellulose 44,500 mg/ 62,400 mg;

Ludipress LCE (lactose monohydrate 94.7-98.3%, povidone 3-4%) 40,000 mg/ 38,500 mg;

Corn starch 8,000 mg/ 11,000 mg;

Colloidal silica 0,500 mg/ 0,600 mg;

Crospovidone (collidon CL) 1,000 mg/ 1,250 mg;

Magnesium stearate 1,000 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.

How to take, the dosage

Biprol is taken orally, in the morning, once a day with some liquid, before, during or after breakfast.

Tablets should not be chewed or crushed into powder. In all cases the mode of administration and the dose are determined individually by the physician taking into account the heart rate and the patient’s condition.

In hypertension and coronary heart disease the drug is administered by 5 mg once a day.

If necessary the dose is increased up to 10 mg once a day. During the treatment of arterial hypertension and angina pectoris the maximum daily dose is 20 mg 1 time per day.

For patients with severe renal dysfunction (creatinine clearance less than 20 ml/min) or with severe hepatic impairment the maximum daily dose is 10 mg 1 time per day.

In such patients the dose should be increased with special caution.

In elderly patients the dose adjustment is not required.

Interaction

The use of allergens used for immunotherapy or allergen extracts for skin tests during therapy with Bisoprolol increases the risk of severe systemic allergic reactions or anaphylaxis.

The simultaneous use with bisoprolol of iodine-containing X-ray contrasting drugs for IV administration increases the risk of anaphylactic reactions.

Concomitant use of bisoprolol with IV phenytoin, drugs for inhalation general anesthesia (hydrocarbon derivatives) increases the severity of cardiodepressive effects and the likelihood of BP decrease.

In concomitant use, bisoprololol alters the effectiveness of insulin and oral hypoglycemic drugs and masks the symptoms of developing hypoglycemia (tachycardia, increased BP).

Concomitant use of bisoprolol decreases clearance of lidocaine and xanthines (except diphylline) and increases their plasma concentrations, especially in patients with initially increased clearance of theophylline due to smoking.

The hypotensive effect of bisoprolol is reduced by NSAIDs (Na+ retention and blockade of prostaglandin synthesis by the kidneys), GCS and estrogens (retention of Na+ ions).

When used concomitantly, cardiac glycosides, methyldopa, reserpine and guanfacine, calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade, heart failure and heart failure.

When used concomitantly with bisoprolol, nifedipine may cause a significant decrease in BP.

When used concomitantly with bisoprololol, diuretics, clonidine, sympatholytics, hydralazine and other hypotensive drugs may lead to excessive BP reduction.

Bisoprolol prolongs the effects of nondepolarizing myorelaxants and the anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics increase the CNS depressant effect of bisoprolol.

The concomitant use of bisoprolol with MAO inhibitors is not recommended due to the significant increase in hypotensive effect (interval between intake of MAO inhibitors and bisoprolol should be at least 14 days).

When used concomitantly with bisoprololol, nonhydrogenated ergot alkaloids, ergotamine increase the risk of peripheral circulatory disorders.

Concomitant use of sulfasalazine increases the plasma concentration of bisoprolol.

Concomitant use of rifampicin decreases T 1/2 of bisoprolol.

Special Instructions

Treatment with the drug is usually long-term.

Before starting treatment, it is recommended to conduct a study of external respiratory function in patients with a history of bronchopulmonary problems.

Patients with bronchospastic disorders may be prescribed bisoprololol in case of intolerance and/or ineffectiveness of other hypotensive drugs, and the dose of the drug should be strictly monitored.

Supervision of patients receiving bisoprolol should include monitoring of heart rate, blood pressure (at the beginning of treatment – daily, then once in 3-4 months),

electrocardiogram, plasma glucose concentration in diabetic patients (once in 4-5 months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months).

The patient should be taught the method of counting heart rate and instructed to consult a physician if it falls below 60 bpm.

In about 20% of patients with angina pectoris beta-adrenoblockers are ineffective.

The main causes are severe coronary atherosclerosis with low ischemic threshold (heart rate less than 100 bpm) and increased left ventricular end-diastolic volume that impairs subendocardial blood flow.

In “smokers” the efficacy of beta-adrenoblockers is lower.

Patients who use contact lenses should consider that against the background of treatment there may be a decrease in tear fluid production.

When used in patients with pheochromocytoma there is a risk of paradoxical arterial hypertension (if effective alpha-adrenoblockade has not been previously achieved).

In thyrotoxicosis bisoprolol may mask certain clinical signs of thyrotoxicosis (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it may exacerbate the symptoms.

In diabetes mellitus, it may mask tachycardia caused by hypoglycemia. Unlike non-selective beta-adrenoblockers, it practically does not increase insulin-induced hypoglycemia and does not delay recovery of blood glucose concentration to normal levels.

If clonidine is used simultaneously, its use can be discontinued only a few days after bisoprolol withdrawal.

The severity of hypersensitivity reactions may increase and the lack of effect of usual doses of epinephrine against the background of a history of aggravated allergology.

If it is necessary to perform a planned surgical intervention the drug should be canceled 48 hours before the start of general anesthesia.

If the patient took the drug before the surgical procedure, he should choose a drug for general anesthesia with minimal negative inotropic effect.

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

Drugs that reduce catecholamine stores (e.g., reserpine) may enhance the effects of beta-adrenoblockers, so patients taking such drug combinations should be under constant medical supervision for arterial hypotension or bradycardia.

In elderly patients with increasing bradycardia (less than 60 bpm), arterial hypotension (systolic blood pressure below 100 mmHg.), AV blockade, bronchospasm, ventricular arrhythmias, severe hepatic and renal dysfunctions it is necessary to reduce the dose or discontinue treatment.

Bisoprolol treatment should not be abruptly interrupted because of the risk of severe arrhythmias and myocardial infarction. Discontinuation is carried out gradually, reducing the dose over 2 weeks or more (the dose is reduced by 25% every 3 to 4 days).

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

The drug should be discontinued before testing the content of catecholamines, normetanephrine and vanillylmindalic acid in blood and urine, antinuclear antibody titer.

Influence on the ability to drive vehicles and operate machinery

During treatment, caution should be exercised when driving vehicles and performing other potentially dangerous activities that require increased concentration and rapid psychomotor reactions.

Synopsis

Round, biconvex, film-coated tablets, white or almost white.

On the cross section the nucleus is white or white with a barely noticeable creamy tint.

Features

Absorption. Absorption is 80-90%, food intake does not affect absorption of the drug.

Maximum concentration in blood plasma is observed after 1-3 hours. Bioavailability is about 90%.

The binding to plasma proteins is about 30%.

Distribution.

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

Metabolism.

Metabolized in the liver with the participation of CYP3A4 (up to 95%) and CYP2D6 isoenzymes.

The effect of “primary passage” through the liver is insignificant (about 10%).

Biotransformation of bisoprolol is not accelerated in patients with thyroid hyperfunction.

Excretion. Total clearance is 15.6±3.2 l/hour, renal clearance is 9.6±1.6 l/hour.

Balanced clearance of bisoprolol is determined by the balance between its excretion through the kidneys unchanged (about 50%) and oxidation in the liver (about 50%) to inactive metabolites, which are then also excreted by the kidneys; less than 2% is excreted through the intestine (with bile).

It does not accumulate in the body. Half-life period is 9-12 hours.

Dependence of bisoprolol pharmacokinetics on dose is linear. Bisoprolol pharmacokinetics is stable and does not depend on the age and sex of the patient.

Pharmacokinetics in special clinical cases Renal insufficiency.

In patients with significant renal function impairment (creatinine clearance less than 20 ml/min) and in patients with anuria half-life may increase more than 2 times.

Hepatic insufficiency.

In case of severe hepatic insufficiency half-life period is increased up to 13-15 hours.

Chronic heart failure.

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

Contraindications

Hypersensitivity to bisoprolol, other drug components and other beta-adrenoblockers; shock (including cardiogenic); pulmonary edema; acute heart failure or CHF in decompensation,

requiring inotropic therapy; AV block of II-III degree, without pacemaker; Sinoatrial blockade; sinus node weakness syndrome; bradycardia (heart rate less than 60 bpm);

Prinzmetal angina; cardiomegaly (without signs of heart failure); severe arterial hypotension (systolic BP less than 100 mm Hg).Hg.

severe bronchial asthma and chronic obstructive pulmonary disease (COPD) in anamnesis; concomitant use of floktafenine, sultopride, monoamine oxidase inhibitors (MAO), except for MAO type B;

Simultaneous intravenous administration of verapamil or diltiazem; severe peripheral circulatory disorders, Raynaud’s syndrome; pheochromocytoma (without simultaneous use of alpha-adrenoblockers);

metabolic acidosis; age under 18 years (effectiveness and safety are not established).
Lactase deficiency, lactose intolerance, lactose/isomaltose malabsorption syndrome (the drug contains lactose).

With caution

Severe hepatic impairment, severe renal insufficiency (creatinine clearance less than 20 ml/min), myasthenia, thyrotoxicosis, diabetes (may mask the symptoms of hypoglycemia), aggravated
allergic reactions.

allergic history, 1st degree AV blockade, depression (including in anamnesis), psoriasis, bronchial asthma, COPD, peripheral circulatory disorders, strict diet.

Side effects

Frequency of the following side effects is given in accordance with the WHO classification: very common – more than 10%; common – more than 1% and less than 10%; infrequent – more than 0.1% or less

1%; rare – more than 0.01% and less than 0.1%; very rare – less than 0.01%, including individual cases.

Central and peripheral nervous system: often – increased fatigue, asthenia, dizziness, headache.

Usually these phenomena occur at the beginning of the treatment, are usually insignificant and disappear within 1-2 weeks; rarely – sleep disturbances, depression; rarely – nightmares, hallucinations, loss of consciousness.

Cardiovascular system:

very common – bradycardia, palpitations; often – marked decrease in blood pressure (especially in patients with CHF), manifestations of angiospasm (increased peripheral circulation disorders,

feeling of cold in the extremities (paresthesias); infrequent – AV conduction disorders (up to complete transverse blockade and cardiac arrest), arrhythmias, worsening

CHF course with the development of peripheral edema (edema of ankles, feet) and dyspnea, orthostatic hypotension, chest pain.

Digestive system disorders:

often – nausea, vomiting, diarrhea, abdominal pain, constipation, dry mouth mucosa; rarely – hepatitis, increased activity of “liver” transaminases (alanine aminotransferase, aspartate aminotransferase), increased concentration of bilirubin.

Respiratory system:

infrequent – laryngo- and bronchospasm in patients with

bronchial asthma or obstructive airways disease; rarely –
allergic rhinitis, nasal congestion.

Musculoskeletal system:

infrequent – muscle weakness, cramps in the calf muscles, arthralgia.

Senses:

rarely – visual impairment, decreased tear production (should be considered while wearing contact lenses), hearing impairment, changes in taste;

very rarely – dry and painful eyes, conjunctivitis.

Skin: rare – increased sweating, psoriasis-like skin reactions, very rare – alopecia, exacerbation of psoriasis.

Endocrine system: rare – hypoglycemia.

Urinary system: rare – impaired potency, decreased libido.

Immune system: rare – the appearance of antinuclear antibodies with unusual clinical symptomatology of lupus-like syndrome, which disappear after treatment.

Allergic reactions: rare – skin hyperemia, skin itching, skin rash, urticaria.

Laboratory: rare – hypertriglyceridemia; very rare – thrombocytopenia, agranulocytosis, leukopenia.

Other: rare – “withdrawal” syndrome (increased angina pectoris attacks, increased blood pressure).

Overdose

Symptoms:

Arrhythmias, ventricular extrasystoles, marked bradycardia, AV blockade, marked BP decrease, chronic heart failure, cyanosis of finger and palm nails, difficulty breathing, bronchospasm, dizziness, fainting, seizures.

Treatment:

Gastric lavage, administration of adsorbents. If necessary, symptomatic therapy: in developed AV-blockade intravenous injection of atropine (1-2 mg), epinephrine, or placement of a temporary pacemaker; in ventricular extrasystole – lidocaine (Class I A drugs are not used).

In case of BP decrease, the patient should be in Trendelenburg position; if there are no signs of pulmonary edema, IV plasma exchange solutions are administered; if ineffective, epinephrine, dopamine, dobutamine (to maintain chronotropic and inotropic action and to eliminate marked BP decrease).

In case of heart failure, cardiac glycosides, diuretics, glucagon are prescribed; in convulsions – intravenous diazepam; in bronchospasm – beta 2 -adreno stimulants by inhalation.

Pregnancy use

The use of Biprol during pregnancy and lactation is possible if the benefit to the mother exceeds the risk of side effects in the fetus and child.

Similarities

Niperten, Concor, Bisogamma, Concor Cor, Coronal, Bidop, Bisoprolol-Teva, Bisoprolol, Biprolol, Bidop Cor