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

Excipients: (cellulose microcrystalline 74.294 mg, silicon dioxide colloid 1.516 mg) 75.810 mg, croscarmellose sodium 1.692 mg, carboxymethyl starch sodium (type A) 4.25 mg, magnesium stearate 0.748 mg.

Description:

Round, biconvex tablets white or almost white, with a risk on one side.

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.

Reduces the activity of renin plasma, reduces the need for myocardium in oxygen, reduces the heart rate (heart rate) (at rest and with exercise). Has antihypertensive, antiarrhythmic and anti-anginal action. Blocking in low doses β₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic action (inhibits conduction and excitability, slows atrioventricular (AV) conductivity).

When the dose is increased above the therapeutic dose, beta₂-adrenoblocking action.

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

The antihypertensive effect is associated with a decrease in cardiac output, sympathetic stimulation of peripheral blood vessels, reduction in activity of the renin-angiotensin system (important for patients with initial hypersecretion renin) sensitivity reduction in response to the lowering of blood pressure (BP) and the influence on the central nervous system ( CNS). With arterial hypertension, the effect occurs after 2-5 days, a stable effect - after 1-2 months.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and a slight decrease in contractility, diastole lengthening, and improvement in myocardial perfusion.

Antiarrhythmic effect is due to 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 slowing AV- conductivity (mainly in the antegrade and, to a lesser extent, retrograde directions through AVnode) and on additional paths.

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it exerts a less pronounced effect on organs containing β₂-adrenoceptors (pancreas, skeletal muscles, smooth musculature of peripheral arteries, bronchi and uterus) and carbohydrate metabolism, does not cause retention of sodium ions in the body. The severity of atherogenic action does not differ from that of propranolol.

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

Pharmacokinetics:

Suction

Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract. Its bioavailability due to an insignificant metabolism "during primary passage" throughThe liver (approximately 10%) is approximately 90% after ingestion. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the dose range from 5 to 20 mg. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution

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

Metabolism

Metabolized by the oxidative pathway without subsequent conjugation. All metabolites have a polarity and are 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, first of all, with the help of isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only a small role.

Excretion

The clearance of bisoprolol is determined by the balance between excretion through the kidneys in an unchanged form (about 50%) and oxidation in the liver (about 50%) to metabolites, which are then excreted by the kidneys. The total ground clearance is 15 l / h. The half-life (T₁_/₂) is 10-12 hours.

There is no data on the pharmacokinetics of bisoprolol in patients with CHF and concurrent with impaired hepatic or renal function.

Indications:

Chronic heart failure.

Contraindications:

- Hypersensitivity to bisoprolol or any of the components;

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

- cardiogenic shock;

- AV-blockade II and III degree without an electrocardiostimulator;

- syndrome of weakness of the sinus node;

- sinoatrial blockade;

- pronounced bradycardia (heart rate <60 beats / min);

- severe arterial hypotension (systolic blood pressure <100 mm Hg);

- severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD) in history;

- severe peripheral arterial circulation and Raynaud's syndrome;

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

- metabolic acidosis;

- children and adolescents under 18 years of age (efficacy and safety not established).

Carefully:

Conducting desensitizing therapy, Prinzmetal angina, hyperthyroidism, diabetes type I and diabetes with considerable fluctuations in blood glucose concentration, AV-blockade of the I degree, expressed renal dysfunction (CC less than 20 ml / min), expressed violations of liver function, psoriasis, restrictive cardiomyopathy, congenital heart disease or heart valve flaw with severe hemodynamic disorders. CHF with myocardial infarction during the last 3 months, a strict diet.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. 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 carefully monitored, and the growth and development of the unborn child should be monitored, and in case of dangerous manifestations in pregnancy or fetus, alternative therapeutic measures should be taken.

You should carefully examine the newborn after delivery. In the first 3 days of life, bradycardia and hypoglycemia may occur.

Data on the isolation of bisoprolol with breast milk or safety of bisoprolol exposure to infants are not available. If you need to use the drug during breastfeeding, you should decide whether to stop breastfeeding.

Dosing and Administration:

Tablets should be taken inwards In the morning, squeezed a small amount of liquid, regardless of food intake. Tablets should not be chewed.

The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin I receptor antagonistsI (in case of intolerance to ACE inhibitors), beta-adrenoblockers, diuretics and, optionally, cardiac glycosides.

A prerequisite for the treatment with Cordinorm Cor is stable CHF without signs of exacerbation.

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

The titration phase

The beginning of treatment with CHF with a drug requires mandatory carrying out of a special phase of titration.

The recommended initial dose is 1.25 mg (¹/₂tablets of 2.5 mg) once a day. Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg, 3.75 mg (1¹/₂2.5 mg tablets), 5 mg, 7.5 mg (3 tablets of 2.5 mg or 1¹/₂5 mg bisoprolol tablets with a risk) and 10 mg once a day. Each subsequent increase in dose should be carried out not less than two weeks later.

During the titration phase, 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.

Change 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 aggravation of symptoms of CHF flow, expressed AD and bradycardia, it is recommended, first of all, to correct the doses of concomitant therapy. It may also be necessary to temporarily reduce the dose of Cordinorm Cor, or to cancel it.

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

If you want to stop taking the drug, the dose should be reduced gradually, since a sudden withdrawal can lead to a sudden deterioration in the patient's condition.

Treatment with the drug is usually long-term.

Special patient groups

When severe renal dysfunction (CC <20 mL / min) and in patients with severe liver disease the maximum daily dose of the drug is 10 mg.Increase in the dose of the drug in such patients should be carried out with extreme caution.

When impaired liver or kidney function of mild to moderate Usually dose adjustment is not required.

When the drug is used in patients old age correction of the dose is not required.

Side effects:

The incidence of adverse reactions listed below was distributed as follows: very often (≥1 / 10); often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000); very rarely (<1/10000, including individual messages).

From the side of the 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 - reduced tearing (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 bradycardia; often - aggravation of symptoms of CHF flow, sensation of cold or numbness in the extremities, pronounced decrease in blood pressure; infrequently infringement AV-conductivity, orthostatic hypotension.

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

Co the sides of the digestive system: 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-adrenoblockers can aggravate the course of psoriasis or cause a psoriasis-like rash.

On the part 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) and alanine aminotransferase (ALT)).

Overdose:

The most frequent symptoms overdose: 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 a pronounced bradycardia: intravenous (iv) atropine administration. 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: iv injection of plasma-substituting solutions and vasopressor preparations.

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

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

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

With hypoglycemia: intravenous injection of dextrose (glucose).

Interaction:

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

Unrecommended combinations

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

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 AVconductivity. AT 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" arterial 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 AVconductivity.

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 AVconductivity and increase the risk of 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 "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.

Nonsteroidal anti-inflammatory drugs can reduce the hypotensive effect of bisoprolol.

Simultaneous use of the drug Cordinorm Cor 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.

Hypotensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can enhance the antihypertensive 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 interrupt treatment with Cordinorm Cor immediately and do not change the recommended dose without first consulting a doctor, as this may cause to temporary deterioration 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 and during its interruption, patients need constant monitoring.

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

- fromdiabetes 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;

- froma touching diet;

- Pdevelopment of desensitizing therapy;

- AV-blockade of the I degree;

- fromprinzmetal prenas;

- Mr.cirrhosis of peripheral arterial blood circulation of mild and moderate degree (at the beginning of therapy there may be an increase in symptoms);

- psoryaz (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 is possible, which requires a higher dose beta₂adrenoblockers.

Allergic reactions: beta-blockers, including the drug Cordinorm Cor, can increase the 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 give 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 before surgery, it should be done gradually and completed 48 hours before the general anesthesia. An anesthesiologist should be alerted that you are taking Cordinorm Cor.

To date, there is insufficient data on the use of bisoprolol in patients with XCH in combination with type 1 diabetes mellitus, expressed kidney and / or liver dysfunction, restrictive cardiomyopathy, congenital heart defects 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.

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

The drug Cordinorm Cor does not affect the ability to drive vehicles according to the results of a study involving patients with ischemic heart disease. However, due to individual reactions, the ability to drive vehicles or work with technically complex mechanisms 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, 2.5 mg.

Packaging:

For 10 or 14 tablets in blisters PVC / PVDC / Al or PVC / PTFE / Al.

For 3, 6, 9 or 10 blisters for 10 tablets, 2 blisters for 14 tablets together with instructions for use in a cardboard bundle.

Storage conditions: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-002962

Date of registration:21.04.2015

Expiration Date:21.04.2020

Date of cancellation:2020-04-21

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

Chanelle Medical Ireland

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp04.02.2018

Illustrated instructions

Instructions

Cordinorm Cor (Cordinorm Cor)