Bisoprolol - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 0.0973 g or 0.0923 g, calcium carbonate - 0.0145 g, microcrystalline cellulose 0.0145 g, croscarmellose sodium (impellose) 0.0029 g, talc 0.00435 g , magnesium stearate - 0.00145 g;

composition of the shell:

for a dosage of 5 mg - Opadrai II White (polyvinyl alcohol - 40%, titanium dioxide - 25%, talc - 20.2%, macrogol (polyethylene glycol) - 14.8%) 0.004841 g, silicone emulsion - 0.000159 g;

for a dosage of 10 mg - Opaprai II White (polyvinyl alcohol - 40%, titanium dioxide - 25%, talc - 20.2%, macrogol (polyethylene glycol) - 14.8%) - 0.004737 g, iron dye oxide red E 172 - 0.000052 g, macrogol (polyethylene glycol) - 0.000052 g, silicone emulsion -0.000159 g.

Description:

Dosage of 5 mg: the tablets covered with a film cover, almost white color, round, biconcave. Insignificant roughness of the surface is permissible. Color of tablets on a cross-section from white to light yellow.

Dosage of 10 mg: pills covered with a film membrane, pink with a weak brownish hue, round, biconvex. Insignificant roughness of the surface is permissible. Color of tablets on a cross-section from white to light yellow.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Selective beta₁-adrenoblokagor without its own sympathomimetic activity, does not possess membrane-stabilizing action. Has a slight affinity for beta₂-adrenoreceptors of smooth muscles of bronchi and vessels, and also to beta₂adrenoreceptors involved in the regulation of metabolism. Consequently, bisoprolol in general, does not affect the resistance of the respiratory tract and the metabolic processes in which beta is involved₂-adrenoceptors.

Selective action of the drug on beta₁-adrenoceptors persists beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of the drug is achieved 3-4 hours after ingestion. With a single application of bisoprolol, the effect persists for 24 hours. The maximum reduction in blood pressure (BP) is achieved 2 weeks after the start of treatment. Bisoprolol reduces the activity of the sympathoadrenal system by blocking the beta adrenoreceptors of the heart.

With a single oral intake in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol reduces the heart rate (heart rate), reduces the shock volume of the heart and, as a consequence, reduces the ejection fraction and the need for myocardium in oxygen.

With prolonged therapy, initially increased total peripheral vascular resistance (OPSS) is reduced. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of beta-blockers.

Pharmacokinetics:

Suction

Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. High bioavailability of the drug (about 90%) is due to a low degree of metabolism in the "first pass" through the liver. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, its plasma concentrations are proportional to the dose taken in the range of 5 to 20 mg. The maximum concentration in the blood is achieved in 2-3 hours.

Distribution

The volume of distribution is 3.5 l / kg. Communication with plasma proteins reaches 30%.

Metabolism

Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys.The main metabolites found in blood plasma and urine, do not show pharmacological activity. Bisoprolol is metabolized by the 95% CYP3A4 isoenzyme and by the enzyme CYP2D6, which plays an insignificant role.

Excretion

About 50% of the drug is metabolized in the liver, metabolites are excreted by the kidneys. 50% of bisoprolol is excreted by the kidneys unchanged. The total ground clearance is 15 liters per hour. The half-life is 10-12 hours.

Indications:

- Arterial hypertension;

- IHD: stable angina;

- CHF.

Contraindications:

- Hypersensitivity to bisoprolol or to any of the components of the drug (see section "Composition"),

- acute heart failure, CHF in the stage of decompensation, requiring inotropic therapy,

- cardiogenic shock,

- atrioventricular (AV) blockade of II and III degree, without an electrocardiostimulator,

- syndrome of weakness of the sinus node,

- sinoatrial blockade,

- pronounced bradycardia (heart rate less than 60 beats / min),

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg)

- severe forms of bronchial asthma,

- marked violations of peripheral arterial blood circulation or Raynaud's syndrome,

- pheochromocytoma (without simultaneous use of alpha-blockers),

- metabolic acidosis,

- age 18 years (insufficient efficacy and safety data in this age group).

Carefully:

Conducting desensitizing therapy, Prinzmetal angina, hyperthyroidism, diabetes type I and diabetes with considerable fluctuations in blood glucose concentration, AV blockade I extent expressed renal failure (creatinine clearance less than 20 mL / min) expressed by human liver, psoriasis, restrictive cardiomyopathy, congenital heart defects, or defect of a heart valve with severe hemodynamic disorders, chronic heart failure myocardial infarction within the last 3 months, severe chronic obstructive pulmonary disease (COPD), a strict diet.

Pregnancy and lactation:

In pregnancy, the drug Bisoprolol should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and / or the child.

Beta-adrenoblockers reduce blood flow in the placenta and can affect the development of the fetus. It is necessary to monitor blood flow in the placenta and uterus, as well as to observe the growth and development of the unborn child and in case of occurrence of adverse events in relation to pregnancyand / or fetus, apply alternative therapies.

You should carefully examine the newborn after delivery. In the first three days of life, bradycardia and hypoglycemia may occur.

There is no data on excretion into breast milk, so the drug Bisoprolol is not recommended for women during breastfeeding. If taking the drug during lactation is necessary, breastfeeding should be discontinued.

Dosing and Administration:

A drug Bisoprolol should be taken once a day with a small amount of liquid, in the morning before breakfast or after it. Tablets should not be chewed and ground into a powder

Arterial hypertension and stable angina

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.

Usually the initial dose is 5 mg of the drug Bisoprolol 1 per day. If necessary, the dose can be increased to 10 mg once a day.

The recommended maximum dose is 20 mg of the drug Bisoprolol 1 per day.

Chronic heart failure

Beta-blockers along with other antihypertensive and diuretic drugs are included in the standard treatment of CHF. Initiation of CHF treatment with a drug Bisoprolol requires mandatory conduct of a special phase of titration and regular medical supervision.

A prerequisite for drug treatment Bisoprolol is stable CHF without signs of exacerbation.

Treatment of CHF with a drug Bisoprolol begins in accordance with the titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i. E. The dose can be increased only if the previous dose is well tolerated.

To ensure the appropriate titration process at the initial stages of treatment, it is recommended that bisoprolol in dosage form: 2.5 mg tablets. The recommended initial dose is 1.25 mg once a day. Depending on the individual tolerability, 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 dose should be carried out not less than two weeks later.

If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible. The recommended maximum dose for the treatment of CHF is 10 mg of Bisoprol 1 time per day.

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

If the patient does not tolerate the recommended maximum dose of the drug, a gradual dose reduction should be considered.

During or after the titration phase, temporary worsening of the course of CHF, arterial hypotension or bradycardia may occur. In this case, it is recommended, first of all, to correct the doses of concomitant therapy. It may also be necessary to temporarily reduce the dose of the drug Bisoprolol or its cancellation.

After stabilization of the patient's condition, a repeated titration of the dose should be performed, or the treatment should be continued.

Duration of treatment for all indications for the use of the drug Bisoprolol

Treatment with drug Bisoprolol is usually a long-term therapy.

Special patient groups

Impaired renal or hepatic function

- If the liver or kidney function is mild or moderate, you usually do not need to adjust the dose.

- At the expressed infringements of function of kidneys (KK less than 20 ml / mines) and at patients with serious diseases the maximum daily dose makes 10 mg. Increasing the dose in such patients should be carried out with extreme caution.

Elderly patients

Correction of the dose is not required.

Children

Since there is insufficient data on the use of the drug Bisoprolol in children, it is not recommended to prescribe the drug to children under 18 years of age.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to the frequency of their development as follows: very often (more than or equal to 1/10), often (more than 1/100, less than 1/10), infrequently (more than 1/1000 , less than 1/100), rarely (more than 1/10000, less than 1/1000), very rarely (less than 1/10000, including individual messages).

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

Common violations: often - asthenia (in patients with CHF), increased fatigue *; infrequently - asthenia (in patients with arterial hypertension or angina pectoris).

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

From the side of the organs of sight: rarely - reduction of lacrimation (should be considered when wearing contact lenses); very rarely - conjunctivitis.

From the organs of hearing: rarely - hearing impairment.

From the cardiovascular system: very often bradycardia (in patients with CHF); often - exacerbation of symptoms of CHF flow (in patients with CHF), a feeling of cold or numbness in the extremities, a marked decrease in blood pressure, especially in patients with CHF; infrequently infringement AV conduction, bradycardia (in patients with arterial hypertension or angina pectoris), worsening of CHF symptoms (in patients with arterial hypertension and angina pectoris), orthostatic hypotension.

From the respiratory system: infrequently bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis; rarely allergic rhinitis.

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

From the musculoskeletal system: infrequently - muscle weakness, muscle cramps.

From the skin: rarely - reactions of hypersensitivity (skin itching, 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 side of the reproductive system: rarely - a violation of potency.

Laboratory indicators: rarely - an increase in the concentration of triglycerides and the activity of "hepatic" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).

* In patients with hypertension or angina pectoris, especially these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

Overdose:

Symptoms: AV blockade, pronounced bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients and, probably, patients with CHF are highly sensitive.

Treatment: In case of an overdose, first of all, it is necessary to stop taking the drug and begin supporting symptomatic therapy:

- with severe bradycardia: intravenous administration of 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 a pronounced decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations;

- at AV blockade: patients should be under constant supervision and receive treatment with beta-adrenomimetics (epinephrine). If necessary - staging an artificial pacemaker;

- with exacerbation of CHF flow: intravenous injection of diuretics, drugs with a positive inotropic effect, vasodilators;

- with bronchospasm: the appointment of bronchodilators, including beta₂adrenomimetics and / or aminophylline;

- with hypoglycemia: intravenous dextrose (glucose).

Interaction:

The effectiveness and tolerability of bisoprolol may be influenced by simultaneous intake of other drugs. This interaction can also occur when two drugs are taken in a short time. The physician should be informed about taking other medications, even if they are taken without the doctor's prescription (ie, OTC drugs).

Unrecommended combinations

Treatment of chronic heart failure

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the heart.

All indications for the use of the drug Bisoprolol

The blockers of "slow" calcium channels (BCCC) such as verapamil and, to a lesser extent, diltiazem, with simultaneous application with bisoprolol may lead to a decrease in myocardial contractility and disruption AV conductivity. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Hypotensive drugs of central action (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 the central sympathetic tone. Abrupt cancellation, especially before the abolition of beta-blockers, may increase the risk of developing "ricochet" arterial hypertension.

Combinations requiring special care

Treatment of arterial hypertension and angina

Antiarrhythmics of Class I with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

All indications for the use of the drug Bisoprolol

BCCC derivatives of dihydropyridine (for example, nifedipine, felodipine, amlodipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out.

Antiarrhythmic drugs of the III class (for example, amiodarone) can increase the violation AV conductivity.

The action of beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, reducing heart rate).

Parasympatomimetics with simultaneous use with bisoprolol may increase the disruption AV conductivity and increase the risk of developing a bradycardia.

The hypoglycemic effect of insulin or hypoglycemic agents for oral ingestion may be enhanced. Symptoms of hypoglycemia - in particular, tachycardia, can be masked or suppressed.Similar interactions are more likely when using non-selectiveMr.th beta-blockers.

Means for general anesthesia may increase the risk of cardiodepressive action, leading to hypotension (see section "Special instructions").

Cardiac glycosides with simultaneous application with bisoprolol may lead to an increase in the time of the impulse and, thus, to the development of bradycardia.

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of bisoprolol.

Simultaneous use of the drug Bisoprolol with beta-adrenomimetics (for example, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics, affecting beta and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) may enhance 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 when using nonselective beta-blockers.

Antihypertensives and other drugs with antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazine) can enhance the hypotensive effect of bisoprolol.

Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.

Monoamine oxidase (MAO) inhibitors, with the exception of MAO B inhibitors, can enhance the antihypertensive effect of beta-blockers. Simultaneous application can also lead to the development of hypertensive crisis.

Special instructions:

Do not abruptly discontinue drug treatment Bisoprolol or change the recommended dose without first consulting a doctor, as this can lead to a temporary worsening of the heart.

Treatment should not be interrupted suddenly, especially in patients with ischemic heart disease. If cessation of treatment is necessary, then the dose should be reduced gradually. At the initial stages of treatment with the drug Bisoprolol patients need constant monitoring.

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

- severe forms of COPD and non-severe forms of bronchial asthma;

- diabetes mellitus with significant fluctuations in blood glucose: symptoms of hypoglycemia, such as tachycardia, palpitations or excessive sweating, may be masked;

- strict diet;

- conducting desensitizing therapy;

- AV blockade of the 1st degree;

- angina of Prinzmetal;

- violations of peripheral arterial blood flow of mild and moderate degree (at the beginning of therapy there may be an increase in symptoms);

- psoriasis (including in the anamnesis);

Respiratory system: with bronchial asthma or COPD simultaneous application of bronchodilating agents is shown. In patients with bronchial asthma, an increase in airway resistance may be required, which will require a high dose of beta₂- adrenomimetics. In patients with COPD bisoprolol, prescribed in complex therapy for the treatment of CHF, should be started with the lowest possible dose, and patients should carefully observe and monitor new symptoms (eg, dyspnea, intolerance to physical activity, cough).

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

General anesthesia: when conducting general anesthesia, the risk of blockade of beta-adrenergic receptors should be considered.If it is necessary to stop therapy with the drug Bisoprolol before surgical intervention, it should be done gradually and completed 48 hours before the general anesthesia. You should warn the anesthesia doctor that you are taking the drug Bisoprolol.

Pheochromocytoma: in patients with a tumor of the adrenal glands (pheochromocytoma), the drug Bisoprolol can be appointed only against the background of the use of alpha-blockers.

Hyperthyroidism: when treating with a drug Bisoprolol symptoms of hyperthyroidism (hyperthyroidism) may be masked.

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

A drug Bisoprolol does not affect the ability to drive vehicles according to the results of the study in patients with ischemic heart disease. However, due to individual reactions, the ability to drive vehicles or work with technically complex machinery can be disrupted. This should be paid special attention at the beginning of treatment, after changing the dose, as well as with the simultaneous use of alcohol.

Form release / dosage:

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

Packaging:

10 tablets per contour cell pack.

For 1, 2, 3, 4 or 5 contour squares with instructions for use in a cardboard pack.

Storage conditions:

In a dry, the dark 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.

Terms of leave from pharmacies:On prescription

Registration number:LP-000745

Date of registration:29.09.2011 / 13.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:BIOKOM, CJSC BIOKOM, CJSC Russia

Manufacturer: & nbsp

BIOKOM, CJSC Russia

Representation: & nbspBIOKOM, CJSCBIOKOM, CJSC

Information update date: & nbsp05.04.2017

Illustrated instructions

Instructions

Bisoprolol (Bisoprolol)