Bisoprolol-SZ, 10 mg 50 pcs.

A selective betahadrenoblocker, without its own sympathomimetic activity, has no membrane stabilizing effect. It reduces plasma renin activity, decreases myocardial oxygen demand, decreases heart rate (HR) (at rest and under load).

It has hypotensive, antiarrhythmic and anti-anginal action. By blocking in low doses betahadrenoreceptors of the heart, it decreases catecholamine-stimulated cAMP formation from ATP, decreases intracellular calcium ion current, has negative chrono-, dromo-, batmo- and inotropic effects, inhibits conduction and excitability and decreases atrioventricular conduction.

If the dose is increased above the therapeutic dose, it has a beta2-adrenoblocating effect.

The total peripheral vascular resistance increases at the beginning of drug administration, in the first 24 h (as a result of reciprocal increase of alpha-adrenoreceptor activity and elimination of beta2-adrenoreceptor stimulation) which returns to baseline in 1-3 days and decreases with long-term administration.

The hypotensive effect is associated with decreased minute blood volume, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (of great importance for patients with initial renin hypersecretion), restoration of sensitivity in response to decreased blood pressure (BP) and the effect on the central nervous system (CNS).

In arterial hypertension, the effect occurs in 2-5 days, stable effect in 1-2 months. Antianginal effect is caused by the decrease of myocardial oxygen demand as the result of heart rate reduction and contractility decrease, prolongation of diastole, improvement of myocardial perfusion.

By increasing left ventricular end-diastolic pressure and increasing ventricular muscle fiber stretch, it may increase oxygen demand, particularly in patients with chronic heart failure.

. The antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of CAMF, arterial hypertension), reduction of the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, in the retrograde direction via AV node) and by additional pathways.

In contrast to non-selective beta-adrenoblockers, when administered in medium therapeutic doses, it has less pronounced effect on the organs containing beta2-adrenoreceptors (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause delay of sodium ions (Na+) in the body; the severity of atherogenic action does not differ from that of propranolol.

Pharmacokinetics

Absorption – 80 – 90%, food intake does not affect absorption. Maximum concentration in blood plasma is observed after 1-3 hours, the binding to blood plasma proteins is about 30%. Hematoencephalic barrier and placental barrier permeability is low, secretion with breast milk is low.

50% of the dose is metabolized in the liver with the formation of inactive metabolites, half-life is 10-12 hours. About 98% is excreted by the kidneys – 50% unchanged, less than 2% in bile.

Indications

Arterial hypertension;

coronary heart disease: prevention of angina attacks.

Pharmacological effect

A selective beta-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect. Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (heart rate) (at rest and during exercise).

It has hypotensive, antiarrhythmic and antianginal effects. By blocking betagadrenoreceptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cAMP from ATP, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect, inhibits conductivity and excitability, and reduces atrioventricular conduction.

When increasing the dose above the therapeutic one, it has a beta2-adrenergic blocking effect.

The total peripheral vascular resistance at the beginning of the use of the drug, in the first 24 hours, increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which returns to the original level after 1-3 days, and decreases with long-term administration.

The hypotensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure (BP) and an effect on the central nervous system (CNS).

In case of arterial hypertension, the effect occurs after 2-5 days, stable effect – after 1-2 months. The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and decreased contractility, prolongation of diastole, and improved myocardial perfusion.

By increasing end-diastolic pressure in the left ventricle and increasing the stretch of ventricular muscle fibers, it can increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown of atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, in the retrograde directions through the AV node) and along additional pathways.

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause retention of sodium ions (Na+) in the body; the severity of the atherogenic effect does not differ from the effect of propranolol.

Pharmacokinetics

Absorption – 80 – 90%, food intake does not affect absorption. The maximum concentration in blood plasma is observed after 1-3 hours, the connection with blood plasma proteins is about 30%. Permeability through the blood-brain barrier and placental barrier is low, secretion into breast milk is low.

50% of the dose is metabolized in the liver with the formation of inactive metabolites, the half-life is 10-12 hours. About 98% is excreted by the kidneys – 50% unchanged, less than 2% with bile.

Special instructions

Use with caution for psoriasis and when there is a family history of psoriasis, diabetes mellitus in the decompensation phase, or with a predisposition to allergic reactions.

Active ingredient

Bisoprolol

Composition

Active substance:

bisoprolol fumarate 5 mg and 10 mg

Excipients:

core – croscarmellose sodium (primellose) – 2.2 mg, 4.4 mg;

povidone (medium molecular weight polyvinylpyrrolidone) – 6.0 mg, 12.0 mg;

pregelatinized starch (starch 1500) – 4.0 mg, 8.0 mg;

colloidal silicon dioxide (Aerosil) – 1.54 mg, 3.08 mg;

talc – 2.0 mg, 4.0 mg;

microcrystalline cellulose – 30.4 mg, 60.8 mg;

lactose (milk sugar) – 47.86 mg, 95.72 mg;

magnesium stearate – 1.0 mg;

shell – Opadry II (polyvinyl alcohol, partially hydrolyzed – 1.2 mg, 2.4 mg; titanium dioxide – 0.67998 mg, 1.35996 mg; talc – 0.444 mg, 0.888 mg; macrogol (polyethylene glycol 3350) – 0.606 mg, 1.212 mg; iron dye oxide (II) yellow – 0.07002 mg, 0.14004 mg).

Pregnancy

Use during pregnancy and lactation is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.

Contraindications

Hypersensitivity to the components of the drug and other beta-blockers, shock (including cardiogenic), collapse, pulmonary edema, acute heart failure, chronic heart failure in the stage of decompensation, atrioventricular (AV) block II-III stage, sinoatrial block, sick sinus syndrome, severe bradycardia, Prinzmetal angina, cardiomegaly (without signs of heart failure), arterial hypotension (systolic blood pressure less than 100 mm Hg, especially with myocardial infarction); severe forms of bronchial asthma and a history of chronic obstructive pulmonary disease; simultaneous use of monoamine oxidase inhibitors (MAO) (with the exception of MAO-B), late stages of peripheral circulatory disorders, Raynaud’s disease), pheochromocytoma (without simultaneous use of alpha-blockers), metabolic acidosis, age under 18 years (efficacy and safety have not been established).

With caution: liver failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, first degree atrioventricular block, depression (including a history), psoriasis, old age.

Side Effects

From the central nervous system: increased fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesia in the extremities (in patients with intermittent claudication and Raynaud’s syndrome), tremor.

From the senses: blurred vision, decreased secretion of tear fluid, dry and sore eyes, conjunctivitis.

From the cardiovascular system: sinus bradycardia, palpitations, myocardial conduction disturbances, AV block (up to the development of complete transverse block and cardiac arrest), arrhythmias, weakening of myocardial contractility, development (worsening) of chronic heart failure (swelling of the ankles, feet; shortness of breath), decreased blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud’s syndrome), chest pain.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, liver dysfunction (dark urine, yellowness of the sclera or skin, cholestasis), changes in taste.

From the respiratory system: nasal congestion, difficulty breathing when prescribed in high doses (loss of selectivity) and/or in predisposed patients – laryngo- and bronchospasm.

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

Allergic reactions: skin itching, rash, urticaria.

From the skin: increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis symptoms.

Laboratory indicators: thrombuitopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, changes in the activity of liver enzymes (increased ALT, AST), bilirubin levels, triglycerides. Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: back pain, arthralgia, weakened libido, decreased potency, withdrawal syndrome (increased angina attacks, increased blood pressure).

Interaction

Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol.

Iodine-containing radiocontrast drugs for intravenous administration increase the risk of developing anaphylactic reactions. Phenytoin when administered intravenously, drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of lowering blood pressure. Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure). Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

The hypotensive effect is weakened by non-steroidal anti-inflammatory drugs (Na+ retention and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (Na+ ion retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers of “slow” calcium channels (verapamil, diltiazem), amiodorone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure. Nifedipine can lead to a significant decrease in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure. Prolongs the effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression.

Concomitant use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect; the break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.

Ergotamine increases the risk of developing peripheral circulatory disorders; sulfasalazine increases the concentration of bisoprolol in plasma; Rifampin shortens the half-life.

Overdose

Symptoms: arrhythmia, ventricular extrasystole, severe bradycardia, AV block, marked decrease in blood pressure, chronic heart failure, cyanosis of fingernails or palms, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage and administration of adsorbents; symptomatic therapy: in case of developed AV block – intravenous administration of 1-2 mg of atropine, epinephrine or installation of a temporary pacemaker; for ventricular extrasystole – lidocaine (class IA drugs are not used); when blood pressure decreases, the patient should be in the Trendelenburg position; if there are no signs of pulmonary edema – intravenous plasma-substituting solutions, if ineffective – administration of epinephrine, dopamine, dobutamine (to maintain chronotropic and inotropic effects and eliminate a pronounced decrease in blood pressure); for heart failure – cardiac glycosides, diuretics, glucagon; for convulsions – intravenous diazepam; for bronchospasm, beta-agonists by inhalation.

Storage conditions

Store in a dry place, protected from light, out of reach of children, at a temperature not exceeding 20 °C.

Shelf life

3 years.

Manufacturer

North Star NAO, Russia