Bisogamma, 5 mg 30 pcs.

A selective beta₁-adrenoblocker without intrinsic sympathomimetic activity, has no membrane stabilizing effect. Reduces blood plasma renin activity, reduces myocardial oxygen demand, reduces HR (at rest and during exercise).

It has hypotensive, antiarrhythmic and antianginal action. In low doses it blocks β₁-adrenoreceptors of heart, decreases catecholamine-stimulated cAMP formation from ATP, decreases intracellular calcium ion current, has negative chrono-, dromo-, batmo- and inotropic action.

When the dose is increased above the therapeutic dose, it has beta₂-adrenoblocking effects.

In the beginning of the drug administration, in the first 24 hours, RPS increases (as a result of reciprocal increase of alpha-adrenoreceptor activity and elimination of β₂-adrenoreceptor stimulation) and returns to baseline in 1-3 days, and decreases with prolonged 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 BP reduction and influence on CNS.

In arterial hypertension, the effect occurs in 2-5 days, stable effect in 1-2 months.

The antianginal effect is caused by 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 can increase oxygen demand, especially in patients with chronic heart failure.

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

When used in moderate therapeutic doses, unlike non-selective beta-adreno-blockers, Bisogamma® has less pronounced effect on organs containing β₂-adrenoreceptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and carbohydrate metabolism, does not cause delay of sodium ions in the body; by severity of atherogenic action it does not differ from propranolol.

Indications

Arterial hypertension.
IHD: prevention of angina attacks.

Pharmacological effect

A selective beta1-blocker without internal sympathomimetic activity and does not have a membrane-stabilizing effect. Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (at rest and during exercise).

It has hypotensive, antiarrhythmic and antianginal effects. By blocking β1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, and has a negative chrono-, dromo-, bathmo- and inotropic effect.

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

At the beginning of the use of the drug, in the first 24 hours, OPSS increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of β2-adrenergic receptors) and after 1-3 days returns to the original level, and with long-term use it decreases.

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 and an effect on the central nervous system.

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 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, Bisogamma® has a less pronounced effect on organs containing β2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause retention of sodium ions in the body; the severity of the atherogenic effect does not differ from propranolol.

Special instructions

Monitoring of patients taking the drug Bisogamma® includes measuring heart rate and blood pressure (at the beginning of treatment – daily, then once every 3-4 months), conducting an ECG, determining blood glucose levels with concomitant diabetes mellitus (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months). The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

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

In approximately 20% of patients with angina, beta blockers are ineffective. The main reasons are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100 beats/min) and increased end-diastolic volume of the left ventricle, which impairs subendocardial blood flow.

When using the drug in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if effective blockade of α-adrenergic receptors is not previously achieved).

In case of thyrotoxicosis, bisoprolol can mask certain clinical symptoms of thyrotoxicosis (for example, tachycardia).

Abrupt withdrawal of Bisogamma® in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.

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

It is possible that the severity of the hypersensitivity reaction may increase and there will be no effect from usual doses of epinephrine against the background of a burdened allergic history.

If planned surgical treatment is necessary, Bisogamma® should be discontinued 48 hours before the start of general anesthesia. If the patient took the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effects.

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

Medicines that reduce the reserves of catecholamines (including reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision for timely monitoring of a pronounced decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases can be prescribed cardioselective adrenergic blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs. An overdose is dangerous due to the development of bronchospasm.

If increasing bradycardia (less than 50 beats/min), a pronounced decrease in blood pressure (systolic blood pressure below 100 mm Hg), or AV blockade is detected in elderly patients, it is necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy if depression develops.

Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmia and myocardial infarction. Cancellation is carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 3-4 days).

When used in combination with clonidine, its use can be discontinued only a few days after bisoprolol is discontinued.

In smoking patients, the effectiveness of beta-blockers is lower.

Patients who use contact lenses should take into account that during treatment with Bisogamma there may be a decrease in the production of tear fluid.

The drug should be discontinued before testing the content of catecholamines, normetanephrine and vanillinmandelic acid in the blood and urine, and titers of antinuclear antibodies.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, patients should be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Bisoprolol

Composition

1 tablet contains:

Active substance:

bisoprolol hemifumarate – 5 mg.

Excipients:

crospovidone,

pregelatinized starch,

microcrystalline cellulose,

colloidal silicon dioxide,

magnesium stearate,

macrogol 6000,

polysorbate 20,

titanium dioxide (E171),

calcium carbonate (E170),

talc,

iron (III) oxide yellow dye (E172),

hypromellose (HPMC 5),

hypromellose (HPMC 50).

Pregnancy

Prescribing the drug during pregnancy and lactation is possible only if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Contraindications

Shock (including cardiogenic).
Collapse.
Pulmonary edema.
Acute heart failure.
Chronic heart failure in the stage of decompensation.
AV block II and III degrees.
Sinoatrial block.
SSSU.
Severe bradycardia.
Prinzmetal’s angina.
Cardiomegaly (without signs of heart failure).
Arterial hypotension (systolic pressure <100 mm Hg, especially with myocardial infarction). Severe forms of bronchial asthma and other obstructive respiratory diseases. Late stages of peripheral circulatory disorders, Raynaud's disease. Pheochromocytoma (without simultaneous use of alpha-blockers). Metabolic acidosis. Depression. Simultaneous administration of MAO inhibitors (except for MAO type B inhibitors). Children and teenagers up to 18 years of age. Hypersensitivity to the components of the drug and other beta-blockers.

With caution: the drug should be prescribed to patients with liver failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, first degree AV block, psoriasis; with indications in the anamnesis of depression, allergic reactions; elderly patients.

Side Effects

From the central nervous system and peripheral 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, convulsions.

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

From the cardiovascular system: sinus bradycardia, palpitations, impaired myocardial conduction, AV block (up to the development of complete transverse block and cardiac arrest), 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 impairment peripheral circulation, 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 the activity of liver enzymes (increased ALT, AST) and bilirubin levels, 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.

From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

From the musculoskeletal system: back pain, arthralgia, cramps in the calf muscles.

From the reproductive system: weakened libido, decreased potency. Allergic reactions: skin itching, rash, urticaria.

Dermatological reactions: increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis symptoms, alopecia.

Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: withdrawal syndrome (increased angina attacks, increased blood pressure), increased triglyceride levels.

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 radiopaque drugs for intravenous administration increase the risk of anaphylactic reactions in patients receiving bisoprolol.

Phenytoin with intravenous administration and drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of a decrease in blood pressure in patients receiving bisoprolol.

Bisoprolol changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Bisoprolol 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 of bisoprolol is reduced by NSAIDs (retention of sodium ions and blockade of prostaglandin synthesis by the kidneys), corticosteroids and estrogens (retention of sodium ions).

Cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmics, when used simultaneously with bisoprolol, increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure.

When used simultaneously with nifedipine, a significant decrease in blood pressure is possible.

When used simultaneously with bisoprolol, diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure.

Bisoprolol prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics enhance the inhibitory effect of bisoprolol on the central nervous system.

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 (including ergotamine), when used simultaneously with bisoprolol, increase the risk of developing peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin reduces T1/2 of bisoprolol.

Overdose

Symptoms: 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 adsorbent medications. Carrying out symptomatic therapy: in case of developed AV blockade – 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 – beta2-adrenergic stimulants by inhalation.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Manufacturer

S.K. Master K&K S.R.L., Romania