Bisoprolol pills 2.5mg 30pcs

Composition

1 film-coated tablet contains:

Composition of the tablet core

Active ingredient: bisoprolol fumarate-2.5 mg.

Excipients: anhydrous calcium hydrophosphate-46.875 mg, microcrystalline cellulose-18.5 mg, corn starch-5.625 mg, magnesium stearate-0.75 mg, colloidal silicon dioxide-0.75 mg.

Composition of the tablet shell: opadray II white (85F18422) (polyvinyl alcohol-40%, titanium dioxide-25%, macrogol 3350-20.2%, talc-14.8% – – 3.0 mg

Pharmacological action

Pharmacotherapy group: beta_-1-adrenoblocker selective

ATX code: C07 AB 07

Pharmacological properties

Pharmacodynamics

Selective beta_-1-adrenoblocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.

Reduces the activity of blood plasma renin, reduces the need for myocardial oxygen, reduces the heart rate (HR) (at rest and during exercise). It has antihypertensive, antiarrhythmic and antianginal effects. Blocking the beta_-1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular flow of calcium ions, and has a negative chrono -, dromo -, batmo – and inotropic effect (inhibits conduction and excitability, slows down atrioventricular (AV) conduction).

If the therapeutic dose is exceeded, it has a beta_-2-adrenoblocking effect.

The total peripheral vascular resistance at the beginning of the drug use in the first 24 hours increases slightly (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors), which returns to the initial value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (which is 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). With arterial hypertension, the effect occurs in 2-5 days, stable effect – in 1-2 months.

The antianginal effect is caused by a decrease in the myocardial oxygen demand as a result of a decrease in heart rate, a slight decrease in contractility, an elongation of the diastole, and an improvement in myocardial perfusion.

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 in 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 medium therapeutic doses, unlike non-selective beta-blockers, it has a less pronounced effect on the organs containing beta_-2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause sodium ion retention in the body. The severity of the atherogenic effect does not differ from that of propranolol.

When used once in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces heart rate and stroke volume and, as a result, reduces the ejection fraction and myocardial oxygen demand.

Pharmacokinetics

Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract. Its bioavailability due to insignificant metabolism “during primary passage” through the liver (approximately 10%) is about 90% after oral use. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, and its plasma concentrations are proportional to the dose taken in the dose range from 5 to 20 mg. The maximum concentration in the blood plasma is reached in 2-3 hours.

Distribution

Bisoprolol is distributed fairly widely. The volume of distribution is 3.5 l / kg. Binding to plasma proteins reaches approximately 30%.

Metabolism

It is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polarized (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine do not show pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is primarily metabolized by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.

Deduction

The clearance of bisoprolol is determined by the balance between its excretion through the kidneys in unchanged form (about 50%) and oxidation in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total ground clearance is 15 l/h. The elimination half-life (T_1/2) is 10-12 hours.

There are no data on the pharmacokinetics of bisoprolol in patients with CHF and concomitant hepatic or renal impairment.

Indications

Chronic heart failure.

Use during pregnancy and lactation

The use of the drug during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

Beta-blockers reduce blood flow to the placenta and can affect fetal development. Blood flow in the placenta and uterus should be closely monitored, as well as the growth and development of the unborn child, and alternative therapeutic measures should be taken in case of adverse events in relation to pregnancy and/or the fetus.

The newborn should be carefully examined after delivery. In the first 3 days of life, symptoms of bradycardia and hypoglycemia may occur.

There are no data on the excretion of bisoprolol in breast milk or the safety of exposure to bisoprolol in infants. If it is necessary to use the drug during breastfeeding, the question of stopping breast-feeding should be decided.

Contraindications

– hypersensitivity to bisoprolol or to any of the excipients;

acute heart failure, chronic heart failure decompensation requiring inotropic therapy;

– cardiogenic shock;

– the atrioventricular (AV) blockade II and III degree (without pacemaker);

– sinoatrial block;

– syndrome of weakness of the sinus node;

– severe bradycardia (heart rate < 60 beats/min);

– severe hypotension (systolic blood pressure < 100 mm Hg. century)

– a severe form of bronchial asthma;

– expressed by human peripheral blood circulation or Raynaud’s syndrome;

metabolic acidosis;

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

– children and adolescence to 18 years (efficacy and safety not established).

Caution

– conducting desensitizing therapies;

– hyperthyroidism;

diabetes mellitus type I diabetes mellitus with significant fluctuations in the concentration of glucose in the blood;

– severe renal insufficiency (creatinine clearance (CC) of less than 20 ml/min);

severe disturbances of liver function;

– psoriasis;

– AV-block I degree;

– Prinzmetal’s angina;

– restrictive cardiomyopathy;

– congenital heart defect or heart valve with severe hemodynamic disturbances;

– chronic heart failure with myocardial infarction within the last 3 months;

– disorders of peripheral blood circulation;

– severe chronic obstructive pulmonary disease;

– bronchospasm (in the anamnesis);

– allergic reactions (history);

General anesthesia;

– a strict diet.

Side effects

The frequency of adverse reactions listed below was distributed as follows (WHO classification): very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000); very rare (

From the cardiovascular system: very often – bradycardia; often – worsening of symptoms of CHF, a feeling of cold or numbness in the extremities, a pronounced decrease in blood pressure; infrequently-violation of AV conduction, orthostatic hypotension.

From the nervous system: often – dizziness, headache; rarely-loss of consciousness.

Mental disorders: infrequently-depression, insomnia; rarely-hallucinations, nightmares.

From the sensory organs: rarely-reduced tear production (should be taken into account when wearing contact lenses), hearing disorders; very rarely-conjunctivitis.

From the respiratory system: infrequently-bronchospasm in patients with a history of bronchial asthma or obstructive airway diseases; rarely-allergic rhinitis.

From the digestive system: often – nausea, vomiting, diarrhea, constipation; rarely-hepatitis.

Musculoskeletal disorders: infrequently-muscle weakness, muscle cramps.

From the genitourinary system: rarely-violation of potency.

From the skin: rarely-hypersensitivity reactions, such as pruritus, skin rash, hyperemia of the skin; very rarely – alopecia, beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

From the laboratory parameters: rarely-increased triglyceride concentration and activity of “hepatic” transaminases in the blood (aspartate aminotransferase (AST), alanine aminotransferase (ALT)).

General disorders and disorders at the injection site: often-asthenia, increased fatigue.

Interaction

The efficacy and tolerability of bisoprolol may be affected by concomitant use of other medications. Such an interaction can also occur in cases where two drugs are taken after a short period of time. The doctor should be informed about taking other medications, even if they are taken without a doctor’s prescription (i. e. over-the-counter medications).

Not recommended combinations

Class I antiarrhythmic agents (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility.

Slow calcium channel blockers (BCCs) such as verapamil and, to a lesser extent, diltiazem, when used concomitantly with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous use of verapamil to patients taking beta-blockers may lead to severe hypotension and AV block.

Antihypertensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before beta-blockers are discontinued, may increase the risk of developing “rebound” hypertension.

Combinations that require special caution

with BMCC dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine) when used concomitantly with bisoprolol may increase the risk of hypotension. In patients with CHF, the risk of subsequent deterioration of the contractile function of the heart cannot be excluded.

Class III antiarrhythmic agents (such as amiodarone) may increase the violation of AV conduction.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

Parasympathomimetics, when used concomitantly with bisoprolol, may increase the violation of AV conduction and increase the risk of bradycardia.

The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia – in particular, tachycardia-can be masked or suppressed. Such interactions are more likely to occur with non-selective beta-blockers.

General anaesthetic agents may increase the risk of cardiodepressive effects, leading to hypotension (see section “Special instructions”).

Cardiac glycosides, when used concomitantly with bisoprolol, can lead to an increase in pulse conduction time, and thus to the development of bradycardia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect of bisoprolol.

Concomitant use of bisoprolol with beta-adrenomimetics (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics that affect beta-and alpha-adrenergic receptors (for example, norepinephrine (norepinephrine), epinephrine (epinephrine)) may increase the vasoconstrictor effects of these agents that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely to occur with non-selective beta-blockers.

Antihypertensive agents, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can increase the hypotensive effect of bisoprolol.

Mefloquine, when co-administered with bisoprolol, may increase the risk of developing bradycardia.

MAO inhibitors (with the exception of MAO B inhibitors) may enhance the antihypertensive effect of beta-blockers. Simultaneous use can also lead to the development of a hypertensive crisis.

How to take, course of use and dosage

Tablets should be taken orally in the morning, washed down with a small amount of liquid, regardless of the time of meal. Tablets should not be chewed.

The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. A prerequisite for treatment with the drug is stable CHF without signs of exacerbation.

During or after the titration phase, there may be a temporary worsening of the course of heart failure, a marked decrease in blood pressure, or bradycardia.

Titration phase

To ensure the following dosage regimen at the initial stages of treatment, it is recommended to use bisoprolol preparations from other manufacturers in the dosage form of 2.5 mg tablets or “5 mg tablets” with two risks.

Initiation of CHF treatment with the drug requires a special titration phase.

The recommended starting dose is 1.25 mg once daily. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg,3.75 mg,5 mg,7.5 mg and 10 mg once a day. Each subsequent increase in the dose should be carried out at least two weeks later.

The maximum recommended dose for CHF is 10 mg of bisoprolol once a day.

During the titration phase, regular monitoring of blood pressure, heart rate, and the severity of CHF symptoms is recommended. Worsening of the symptoms of CHF is possible from the first day of use of the drug.

Changing the reception mode

If the patient does not tolerate the maximum recommended dose of the drug, a gradual dose reduction is possible.

In case of worsening of the symptoms of CHF, severe blood pressure and bradycardia, first of all, it is recommended to adjust the doses of concomitant therapy. You may also need to temporarily reduce the dose of the drug or cancel it.

After stabilization of the patient’s condition, repeat titration should be performed, or continue treatment.

If discontinuation of the drug is required, then the dose of the drug should be reduced gradually, since abrupt withdrawal may lead to a sudden deterioration of the patient’s condition.

Treatment with the drug is usually long-term.

Special patient groups

In severe renal insufficiency (CC Increasing the dose of the drug in such patients should be carried out with extreme caution.

In cases of mild or moderate hepatic or renal impairment, no dose adjustment is usually required.

When using the drug in elderly patients, no dose adjustment is required.

Overdose

Symptoms: severe bradycardia, AV block, marked decrease in blood pressure, acute heart failure, hypoglycemia, bronchospasm.

Sensitivity to a single high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with CHF are highly sensitive.

Treatment: first of all, you should stop taking the drug and start supportive symptomatic therapy. With severe bradycardia-intravenous use of atropine. If the effect is insufficient, you can use caution to introduce a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily install an artificial pacemaker.

With a pronounced decrease in blood pressure – intravenous use of plasma-substituting solutions and vasopressors.

With hypoglycemia, intravenous use of dextrose (glucose), glucagon may be indicated.

With AV block, patients should be constantly monitored and treated with beta-adrenomimetics, such as epinephrine (epinephrine). If necessary, an artificial pacemaker can be installed.

If the course of CHF worsens, intravenous use of diuretics, drugs with a positive inotropic effect, as well as vasodilators is recommended.

With bronchospasm-the appointment of bronchodilators, including beta_-2-adrenomimetics and / or aminophylline.

Description

Tablets of round, biconvex shape, covered with a film-coated white or almost white color.

Special instructions

Do not abruptly discontinue treatment with bisoprolol or change the recommended dose without first consulting your doctor, as this may lead to temporary deterioration of heart activity. Treatment should not be interrupted abruptly, especially in patients with CHD. If discontinuation of treatment is necessary, the dose should be reduced gradually.

At the initial stages of bisoprolol treatment, patients need constant monitoring.

The drug should be used with caution in the following cases::

– severe COPD and mild forms of bronchial asthma;

diabetes mellitus with significant fluctuations in the concentration of glucose in the blood: symptoms expressed lower concentrations of glucose (hypoglycemia), such as tachycardia, palpitations or sweating, can be masked;

– a strict diet;

– conducting desensitizing therapies;

– AV-block I degree;

– Prinzmetal’s angina;

– disorders of the peripheral arterial circulation of mild and moderate degree (at the beginning of therapy may be increased symptoms);

– psoriasis (including in the anamnesis).

Respiratory system: concomitant use of bronchodilators is indicated in patients with asthma or COPD. Patients with asthma may have increased airway resistance, which will require a higher dose of beta_-2-adrenomimetics. In patients with COPD, bisoprolol, which is prescribed in combination therapy for the treatment of heart failure, should be started with the lowest possible dose, and patients should be carefully monitored for new symptoms (for example, shortness of breath, exercise intolerance, cough).

Allergic reactions: beta-blockers, including bisoprolol, may increase sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the action of beta-blockers. Epinephrine (epinephrine) therapy does not always produce the expected therapeutic effect.

General anesthesia: when performing general anesthesia, the risk of beta-adrenergic blockage should be considered. If it is necessary to stop bisoprolol therapy before surgery, this should be done gradually and completed 48 hours before general anesthesia. The anaesthetist should be advised about bisoprolol therapy.

Pheochromocytoma: in patients with an adrenal tumor (pheochromocytoma), bisoprolol can be prescribed only against the background of the use of alpha-blockers.

Hyperthyroidism: when treated with bisoprolol, the symptoms of thyroid hyperfunction (hyperthyroidism) may be masked.

Influence on the ability to drive vehicles and mechanisms

The drug Bisoprolol does not affect the ability to drive vehicles according to the results of the study in patients with CHD. However, due to individual reactions, the ability to drive vehicles or work with technically complex mechanisms may be impaired. This should be paid special attention at the beginning of therapy, after changing the dose, as well as when drinking alcohol at the same time.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Bisoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Heart Failure, Arrhythmia