Concor Cor - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate, anhydrous - 134.0 mg; corn starch, fine powder - 15 mg; silicon dioxide colloidal, anhydrous - 1.5 mg; cellulose microcrystalline - 10.0 mg; crospovidone - 5.5 mg; magnesium stearate 1.5 mg.

Film Sheath: gand promromellose 2910/15 - 2.20 mg, macrogol-400 - 0.53 mg, dimethicone-100 - 0.11 mg, titanium dioxide (E 171) - 1.22 mg.

Description:

White, heart-shaped, biconvex tablets, covered with a shell, with a risk on both sides.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Selective beta₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. He has only 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 involved₂adrenoreceptors. Selective action of the drug on beta₁-adrenoceptors persists beyond the therapeutic range.

In a single application in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol reduces the heart rate (heart rate), stroke volume of the heart and, as a result, reduces the ejection fraction and the need for myocardium in oxygen. With prolonged therapy, initially increased total peripheral vascular resistance (OPSS) is reduced.

Pharmacokinetics:

Suction. Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to an insignificant metabolism "during the first passage" through the liver (at about 10%) is about 90% after ingestion. Eating does not affect bioavailability.

Bisoprolol shows linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the range of 5 to 20 mg. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution. Bisoprolol distributed fairly widely. The volume of distribution is 3.5 l / kg. The connection with plasma proteins is approximately 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. Data obtained as a result of experiments with microsomes of human liver in vitro, show that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only a small role.

Excretion. Bisoprolol clearance is determined by the balance between excretion by the kidneys in unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. The total ground clearance is 15 liters per hour. The half-life is 10-12 hours.

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous impairment of liver or kidney function.

Indications:Chronic heart failure

Contraindications:

Hypersensitivity to biseoprolol or to any of the auxiliary substances (see section "Composition"),
acute heart failure, chronic heart failure 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,
expressed 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, type I diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, AV blockade of I degree, expressed renal failure (CC less than 20 ml / min), expressed liver function abnormalities, psoriasis, restrictive cardiomyopathy , congenital heart disease or heart valve disease with severe hemodynamic disorders, CHF with myocardial infarction during the last 3 months, severe forms of chronic obstructive pulmonary disease, horny diet.

Pregnancy and lactation:

In pregnancy, the Concor® Cor preparation should be recommended for use only if the benefit to the mother exceeds the risk of side effects in the fetus and / or the child.

As a rule, beta-adrenoblockers reduce blood flow in the placenta and can affect the development of the fetus. Blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored, and alternative therapeutic measures taken if pregnancy and / or fetus are undesirable. 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 the isolation of bisoprolol in breast milk. Therefore, taking Concor® Cor is not recommended for women during lactation. If taking the drug during lactation is necessary, breastfeeding should be discontinued.

Dosing and Administration:

Concor Cor tin tablets should be taken once a day with a small amount of liquid in the morning before breakfast, during or after it. Tablets should not be chewed or ground into a powder.

Standard treatment of CHF scheme involves the use of inhibitors of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor antagonists II (in the case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. The beginning of treatment with CHC with Concor® Cor requires mandatory special phase of titration and regular medical supervision.

A prerequisite for the treatment with Concor® Cor is Constant Chronic Heart Failure without signs of exacerbation.

Treatment with CHC with Concor® Cor begins with the following 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. 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 maximum recommended dose for CHF is 10 mg of Concor Cor preparation once a day.

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

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

During the titration phase or after it, 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 Concor Cor, or to cancel it.

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

Treatment with Concor® Cor is usually a long-term therapy.

Special patient groups

Violation ofFunctions kidney or liver:

- 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 of a liver the maximum daily dose makes 10 mg. Increase in 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 not enough data on the use of the drug Concor® Cor in children, it is not recommended to prescribe the drug to children under 18 years of age.

To date, there is insufficient data on the use of Concor Cor preparation in patients with CHF in combination with type 1 diabetes mellitus, expressed renal and / or liver dysfunction, restrictive cardiomyopathy, congenital heart disease or heart valve disease with severe hemodynamic disorders. Also, sufficient data have not yet been obtained regarding patients with CHF with myocardial infarction during the last 3 months.

Side effects:

The incidence of adverse reactions listed below was determined as follows:

- very often ≥ 1/10;

- often ≥ 1/100, <1/10;

- infrequently ≥ 1/1000, <1/100;

- rarely ≥1 / 10,000, <1/1000;

- very rarely <1/10 000.

central nervous system

Often: dizziness, headache.

Rarely: loss of consciousness.

Common violations

Often: asthenia, increased fatigue.

Mental disorders

Infrequently: depression, insomnia.

Rarely: hallucinations, nightmares.

From the side of the organ of vision

Rarely: decreased lacrimation (should be considered when wearing contact lenses).

Very rarely: conjunctivitis.

From the side of the hearing organ

Rarely: hearing impairment.

From the side of the cardiovascular system

Very often: a bradycardia.

Often: aggravation of symptoms of CHF; a feeling of cold or numbness in the extremities, a pronounced decrease in blood pressure.

Infrequently: violation AV conduction, orthostatic hypotension.

From the respiratory system

Infrequent: bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis.

Rarely: allergic rhinitis.

From the side of the digestive tract

Often: nausea, vomiting, diarrhea, constipation.

Rarely: hepatitis.

From the musculoskeletal system

Infrequently: muscle weakness, muscle cramps.

From the skin

Rarely: hypersensitivity reactions, such as pruritus, 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)).

Overdose:

Symptoms

The most common symptoms of an overdose are: 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

When an overdose occurs, first of all, it is necessary to stop taking the drug and begin supporting symptomatic therapy.

With severe bradycardia: intravenous 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 marked decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations.

When AV blockade: patients should be under constant supervision and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.

With exacerbation of the course of CHF: intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

When bronhospazme: the appointment of bronchodilators, including beta₂adrenomimetics and / or aminophylline.

When 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 doctor should be informed about the acceptance of other drugs, even if they are received without a doctor's prescription (ie, non-prescription drugs).

Unrecommended combinations

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.

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

Combinations requiring special care

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, decreasing 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. Such interactions are more likely when using nonselective 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 timing 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 Concor Cor preparation 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-adrenoreceptors (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, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the hypotensive effect of bisoprolol.

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

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 interrupt treatment with Concor® Cor immediately and do not 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 Concor® Cor, 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 concentration: symptoms of marked decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations or excessive sweating, may be masked;
Strict diet;
Desensitizing therapy;
AV blockade of the 1st degree;
Angina of princemetal;
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 higher dose of beta2-adrenomimetics. In patients with COPD bisoprolol, prescribed in complex therapy for the treatment of heart failure, should begin with the lowest possible dose, and patients carefully monitor for the appearance of new symptoms (eg, dyspnea, intolerance to physical exertion, coughing).

Allergic reactions: beta-blockers, including the drug Concor® Cor, can increase sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the action of beta-adrenoblockers. 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 discontinue therapy with Concor® Cor before surgery, it should be done gradually and completed 48 hours before general anesthesia. An anesthesiologist should be warned that you are taking Concor® Cor.

Pheochromocytoma: in patients with a tumor of the adrenal glands (pheochromocytoma), the preparation Concor® Cor can be prescribed only against the background of the use of alpha-adrenoblockers.

Hyperthyroidism: in the treatment with Concor® Cor, the symptoms of hyperthyroidism (hyperthyroidism) of the thyroid gland can be masked.

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

The preparation Concor® Cor 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:

Film-coated tablets, 2.5 mg.

Packaging:

10 tablets per blister of aluminum foil and PVC; 3 blisters together with instructions for use are placed in a cardboard box.

For 14 tablets in a blister of aluminum foil and PVC; 1 blister together with instructions for use are placed in a cardboard box.

25 tablets per blister of aluminum foil and PVC; 2 blisters together with instructions for use are placed in a cardboard box.

30 tablets per blister of aluminum foil and PVC; 1 blister together with instructions for use are placed in a cardboard box.

When the drug is packaged at a Russian company, Nanolek LLC

30 tablets per blister of aluminum foil and PVC; 1 or 2 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 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:П N013955 / 01

Date of registration:06.12.2007 / 08.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:Merck KGaAMerck KGaA Germany

Manufacturer: & nbsp

MERCK, KGaA Germany

Representation: & nbspMERK, LLCMERK, LLCRussia

Information update date: & nbsp03.02.2018

Illustrated instructions

Instructions

Concor® Cor (Concor® Cor)