Coronal 10 mg tablets No. 60 *

Coronal (CORONAL) instructions for use

Composition

active ingredient: bisoprolol; 1 tablet contains 5 mg or 10 mg of bisoprolol fumarate;

Excipients:

Coronal 5: microcrystalline cellulose, corn starch, sodium lauryl sulfate, silicon dioxide colloid, magnesium stearate, hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide yellow (E172)

Coronale 10: microcrystalline cellulose, corn starch, sodium lauryl sulfate, silicon dioxide colloid, magnesium stearate, hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide red (E172).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

Coronale 5: light yellow biconvex tablets coated with a film membrane, which have a resolution to the dash on one side.

Coronale 10: light pink biconvex tablets coated with a film membrane, which have a resolution to the dash on one side.

Pharmacological group

Selective blockers of b-adrenergic receptors. ATX Code C07A B07.

Pharmacological properties

Pharmacodynamics. Bisoprolol is a highly selective ß 1 adrenoblocker. Has no ICA and clinically expressed membrane-stabilizing properties. The drug has a very low affinity for the ß2 receptors of the smooth muscles of the bronchi and vessels, as well as the ß2 receptors that participate in metabolic regulation. Thus, bisoprolol does not affect the resistance of the respiratory tract and ß2 mediated metabolic effects. The selectivity of bisoprolol relative to ß 1 -adrenoceptors extends beyond the therapeutic range of doses.

Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of bisoprolol occurs 3-4 hours after ingestion. The elimination half-life is 10-12 hours, which results in a 24-hour effectiveness after a single dose. The maximum antihypertensive effect is achieved after 2 weeks of admission.

With intensive therapy in patients with coronary heart disease without chronic heart failure, bisoprolol reduces cardiac output and myocardial oxygen demand by reducing heart rate and stroke volume. With prolonged therapy, increased peripheral resistance decreases. Also, the mechanism of action of reducing renin activity in plasma is the basis of the antihypertensive effect of ß-blockers.

Bisoprolol inhibits the response to sympathoadrenergic activity by blocking cardio-ß 1 receptors. This leads to a slowing of the heartbeat and a decrease in the contractile function of the myocardium, a reduction in myocardial oxygen demand. This achieves the desired effect in patients with angina and ischemic heart disease.

Pharmacokinetics.

Absorption. After ingestion, more than 90% of bisoprolol is absorbed from the gastrointestinal tract. Absorption does not depend on food intake. The value of the first pass effect is ≤ 10%. Bioavailability is about 90%.

Distribution. The volume of distribution is 3.5 l / kg. Binding to plasma proteins is about 30%.

Metabolism and excretion. Bisoprolol is excreted from the body in two ways: 50% is metabolized in the liver with the formation of inactive metabolites and is excreted by the kidneys, 50% is excreted by the kidneys unchanged. The total clearance of bisoprolol is 15 l / h. Due to the long half-life (10-12 hours) the drug retains a therapeutic effect for 24 hours when applied once a day.

Linearity. The pharmacokinetics of bisoprolol is linear, its indices are independent of age.

Special groups of patients. Since bisoprolol is excreted from the body by kidneys and liver equally in patients with impaired liver function or renal dysfunction, correction of the dosing regimen is not required. Pharmacokinetics in patients with stable chronic heart failure and with impaired liver or kidney function has not been studied. In patients with chronic heart failure of functional class III (NYHA), the level of bisoprolol in the blood plasma is higher and the half-life is longer compared to healthy volunteers. The maximum plasma concentration in the equilibrium state is 64 + 21 ng / ml with a daily dose of 10 mg and a half-life of 17 + 5:00.

Clinical characteristics.

Indications

• Arterial hypertension;
• ischemic heart disease (angina)
• chronic heart failure with systolic dysfunction of the left ventricle in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Contraindications

• Acute congestive heart failure or heart failure in a state of decompensation, which requires inotropic therapy;
• cardiogenic shock
• blockade of II and III degree (with the exception of this in patients with an artificial pacemaker)
• syndrome of weakness of the sinus node;
• sinoatrial block
• symptomatic bradycardia
• symptomatic arterial hypotension
• severe form of bronchial asthma
• late stages of impaired peripheral circulation or Raynaud's disease
• pheochromocytoma, was not treated;
• metabolic acidosis,
• hypersensitivity to bisoprolol or other components of the drug.

Interaction with other drugs and other interactions

Combinations that are not recommended.

Treatment of chronic heart failure.

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): it is possible to potentiate the effect by AV-conduction and enhance the negative inotropic effect.
All indications.

Calcium antagonists (verapamil groups, to a lesser extent diltiazem): a negative effect on the contractile function of the myocardium and AV-conduction. The administration of verapamil in patients taking ß-blockers can lead to severe arterial hypotension and AV blockade.
Hypotensive drugs of central action (clonidine, methyldopa, moxonidine, rilmenidine): may worsen the course of heart failure due to a decrease in the central sympathetic tone (decrease in heart rate and cardiac output, vasodilation).Sudden abolition of the drug, especially if it is preceded by the abolition of ß-adrenoceptor blockers, may increase the risk of ricochet hypertension.

Combinations that should be used with caution.

Treatment of arterial hypertension or coronary heart disease (angina pectoris).

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): it is possible to potentiate the effect by AV-conduction and enhance the negative inotropic effect.

All indications.

Calcium antagonists of the dihydropyridine type (for example, nifedipine, felodipine, amlodipine): an increased risk of arterial hypotension is possible. The possibility of an increase in the negative effect on the inotropic function of the myocardium in patients with heart failure is not ruled out.
Class III antiarrhythmic drugs (amiodarone): Potentiation of the effect on AV-conduction is possible.
ß-blockers of local action (for example, contained in eye drops for the treatment of glaucoma): it is possible to enhance the systemic effects of bisoprolol.
Parasympathomimetics: AV-conduction time may be longer and the risk of bradycardia may be increased.
Insulin and oral hypoglycemic agents: increased hypoglycemic action. Blockade of β-adrenergic receptors can mask symptoms of hypoglycemia.
Means for anesthesia: the risk of oppression of myocardial function and arterial hypotension increases (see Section "Features of application").
Cardiac glycosides: decrease in heart rate, increase in AV conduction time.
Nonsteroidal anti-inflammatory drugs (NSAIDs): possible weakening of the hypotensive effect of bisoprolol.
ß-sympathomimetics (eg, orciprenaline, isoprenaline, dobutamine): use in combination with the drug may result in a decrease in the therapeutic effect of both agents. To treat allergic reactions, higher doses of epinephrine may be required.
Sympathomimetics, which activate α- and ß-adrenergic receptors (for example, adrenaline, noradrenaline): the manifestation of α-adrenergic receptor mediated vasoconstrictive effect, which leads to increased blood pressure and increased intermittent claudication. Such an interaction is likely when using non-selective ß-blockers.
When combined with antihypertensive agents and agents, hypotensive action (eg, tricyclic antidepressants, barbiturates, phenothiazine) may increase the risk of arterial hypotension.

Combinations are possible.

Mefloquine: there may be an increased risk of bradycardia.
MAO inhibitors (except MAO type B inhibitors): increased antihypertensive effect of ß-blockers, but there is a risk of developing a hypertensive crisis.

Application features

Treatment of stable chronic heart failure with bisoprolol should begin with the titration phase.

Patients with coronary heart disease should not be discontinued suddenly without the need, as this can lead to transient deterioration. Initiation and discontinuation of bisoprolol treatment requires regular monitoring.

At present, there is no sufficient therapeutic experience in the treatment of heart failure in patients with the following diseases and pathological conditions: Type I diabetes mellitus (insulin-dependent), severe renal dysfunction, severe liver dysfunction, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant valve valvular disease , myocardial infarction within the last 3 months.

The drug should be used with caution to patients under such conditions:

• bronchospasm (with bronchial asthma, obstructive airways diseases);
• diabetes mellitus with significant fluctuations in blood glucose, with the symptoms of hypoglycemia (tachycardia, palpitation, sweating) can be hidden;
• strict diet;
• carrying out desensitization. Like other ß-blockers, bisoprolol can increase sensitivity to allergens and increase the severity of anaphylactic reactions. In such cases, treatment with epinephrine does not always produce a positive therapeutic effect;
• blockade of the 1st degree;
• angina of Prinzmetal;
• obliterating diseases of peripheral arteries (at the beginning of therapy, it is possible to increase complaints)
• general anesthesia.

In patients who are scheduled for general anesthesia, the use of ß-blockers reduces the incidence of arrhythmia and myocardial ischemia during the introduction to anesthesia, intubation and postoperative period. It is recommended to continue the use of ß-blockers in the perioperative period. It is necessary to warn an anesthesiologist about admission of ß-adrenergic blockers, since the doctor should take into account the potential interaction with other drugs that can lead to bradyarrhythmia, reflex tachycardia and a decrease in the capacity of the reflex mechanism to compensate for blood loss. In case of cancellation of bisoprolol before surgery, the dose should be gradually reduced and discontinued 48 hours before general anesthesia.

Combinations of bisoprolol with calcium antagonists of the verapamil or diltiazem group, with class I antiarrhythmic drugs and with central-action antihypertensives are not recommended (see Section "Interaction with Other Drugs and Other Interactions").

Despite the fact that the ß-blockers (ß1) have a lower cardioselective effect on lung function than non-selective ß-blockers, they should be avoided, like all ß-blockers, in obstructive airway diseases, if there are no compelling reasons for conducting therapy. If necessary, the drug should be used with caution. In patients with obstructive airways disease, bisoprolol should be started with a low possible dose, and patients should be monitored for new symptoms (such as dyspnoea, intolerance to physical activity, cough).

In bronchial asthma or other chronic obstructive pulmonary diseases, can cause symptoms, concomitant therapy with bronchodilators is indicated. In some cases, patients with bronchial asthma may require higher doses of ß2-sympathomimetics due to increased airway resistance.

Patients with psoriasis (including anamnesis) ß-blockers (eg, bisoprolol) are prescribed after a thorough benefit / risk ratio.

Patients with pheochromocytoma are prescribed only after the administration of α-adrenoreceptor therapy. Symptoms of thyrotoxicosis can be masked against the background of taking the drug. With the use of the drug, a positive result can be observed during doping control.

Use during pregnancy or lactation.

Pregnancy. Bisoprolol has pharmacological properties that can lead to adverse effects on pregnancy and / or fetus / newborn development. As a rule, ß-adrenoblockers reduce placental blood flow, which can cause a delay in intrauterine development, intrauterine death, spontaneous abortion or premature birth. Side effects can occur in the fetus and the newborn (eg, hypoglycemia, bradycardia). If treatment with ß-blockers is necessary, it is desirable that this is an ß 1 -selective adrenoblocker.

During pregnancy, the drug is used only when the expected benefit to the mother exceeds the potential risk to the fetus.It is necessary to monitor uteroplacental blood flow and fetal growth. In case of adverse effects on pregnancy or fetus, alternative treatment should be considered.

After delivery, the newborn should be carefully monitored. Symptoms of hypoglycemia and bradycardia can be expected within the first 3 days.

The period of breastfeeding. There are no data on the excretion of bisoprolol into breast milk, so it is not recommended to use the drug during breastfeeding.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

In studies involving patients with ischemic heart disease, the drug did not affect the ability to drive. However, in individual cases, the drug may affect the ability to drive vehicles or work with mechanisms. Particular attention should be paid at the beginning of treatment, with a change in the dose of the drug or in the interaction with alcohol.

Dosing and Administration

The drug should be taken without chewing, in the morning on an empty stomach, during or after breakfast, washed down with a small amount of liquid.

Arterial hypertension; ischemic heart disease (angina).

Treatment should be started gradually from low doses with a subsequent increase in the dose. The recommended dose is 5 mg (1 tablet of 5 mg) per day. With a moderate degree of hypertension (diastolic pressure up to 105 mmHg), a dose of 2.5 mg (½ tablets of the drug at 5 mg) is appropriate.

If necessary, the daily dose can be increased to 10 mg (1 tablet of 10 mg) per day. Further increase in the dose is justified only in exceptional cases. The maximum recommended dose is 20 mg per day.

Dose adjustments are set individually, depending on the pulse rate and therapeutic benefit.

Chronic heart failure with systolic dysfunction of the left ventricle in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Standard therapy for chronic heart failure: ACE inhibitors (or angiotensin receptor blockers in case of intolerance to ACE inhibitors), β-adrenoreceptor blockers, diuretics and, if necessary, cardiac glycosides.

The drug is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.

Therapy should be conducted by a doctor with experience in the treatment of chronic heart failure.

Treatment of stable chronic heart failure with the drug begins in accordance with the titration scheme presented below and can be adjusted depending on the individual reactions of the body.

1,25 mg * of bisoprolol fumarate 1 time per day for 1 week, if well tolerated, increase to
2.5 mg * of bisoprolol fumarate 1 time per day for the next 1 week, if well tolerated, increase to
3.75 mg * bisoprolol fumarate 1 time per day for the next 1 week, if well tolerated, increase to
5 mg of bisoprolol fumarate once a day for the next 4 weeks, if well tolerated, increase to
7.5 mg of bisoprolol fumarate once a day for the next 4 weeks, if well tolerated, increase to
10 mg of bisoprolol fumarate once a day as maintenance therapy.
* At the beginning of therapy for chronic heart failure, 2.5 mg is recommended. To obtain a dose of 2.5 mg tablet drug at 5 mg can be divided in half.

The maximum recommended dose of bisoprolol fumarate is 10 mg 1 time per day.

During the titration phase control necessary for the following vital signs (blood pressure, heart rate), and the progression of heart failure symptoms. Symptoms can develop from the first day after the start of treatment.

Modification of treatment.

If the maximum recommended dose is not well tolerated, gradual dose reduction is possible. If, during the titration phase or after there is a gradual worsening of heart failure, hypotension develops or aetiology, correction recommended dose, which may require temporary dose reduction of bisoprolol or may suspend treatment. After stabilization of the patient always should consider re-initiation of treatment with bisoprolol.

Should not stop treatment with the drug abruptly, especially in patients with ischemic heart disease, as it may lead to a deterioration in the patient's condition. In case of need of treatment to complete slowly, gradually reducing the dose (e.g., reducing the dose twice weekly).

Treatment of stable chronic heart failure is usually long.

The course of treatment lasting and depends on the nature and severity of the disease.

Patients with hepatic and / or renal insufficiency.

Arterial hypertension; cardiac ischemia. For patients with impaired mild to moderate hepatic or renal function selection gravity doses generally do not need. For patients with severe renal failure (creatinine clearance less than 20 mL / min) and patients with severe liver failure dose should not exceed 10 mg daily dose. There are limited data on the use of bisoprolol in patients on dialysis. Need to modify the dosing regimen is not.

Chronic heart failure No pharmacokinetic bisoprolol in patients with chronic heart failure simultaneously with impaired hepatic or renal function, therefore, necessary to increase the dose with caution.

Elderly patients do not require dose adjustment.

Children. Clinical data on the efficacy and safety of the drug have no children, so you should not use the drug in this category of patients.

Overdose

Symptoms.

In overdose (e.g., a daily dose of 15 mg instead of 7.5 mg) cases of AV-blockade III extent, dizziness and bradycardia were recorded. Frequent signs ß-blocker overdose is bradycardia, hypotension, congestive heart failure, hypoglycemia, and bronchoconstriction. Currently, there are several cases of overdose in patients with hypertension and / or coronary heart disease (the maximum dose - 2000 mg bisoprolol). Marked bradycardia and / or hypotension. All patients recovered. There is wide variation in individual sensitivity to a single high dose of bisoprolol in heart failure patients may be more sensitive to the drug. Therefore, treatment should begin with a gradual increase in dose (see.CATEGORY "Dosage and administration").

Treatment.

When drug overdose treatment is stopped and a supportive and symptomatic therapy. There are limited data bisoprolol difficult to dialysis. If you suspect an overdose, in accordance with the expected pharmacologic actions and based on the recommendations for other ß-blockers should consider the following general measures.

When bradycardia: atropine. If no response, isoprenaline administered with caution or other preparation with a positive chronotropic effect. In exceptional cases, it may require the introduction of transvenous pacemaker.

If hypotension: intravenous fluids and vasoconstrictors. Glucagon may be useful.

In atrioventricular block II and III degree: careful monitoring and administering isoprenaline infusion or administration transvenous pacemaker.

During exacerbation of chronic heart failure: administering diuretics, inotropic agents, vasodilators.

When bronchospasm: bronchodilators (e.g., isoprenaline), ß 2 agonists and / or aminophylline.

When hypoglycemia: intravenous glucose.

Adverse Reactions

Side effects by frequency of occurrence is classified in categories:

very common (> 1/10), common (> 1/100 and <1/10), uncommon (> 1/1000 and <1/100), rare (> 1/10000 and <1/1000), very rare (<1/10000) unknown (not defined by the frequency data).

From the heart.

Very common: bradycardia (in patients with chronic heart failure patients).

Often, signs of worsening of heart failure (in patients with chronic heart failure patients).

Infrequently violation of AV conduction, bradycardia (in patients with hypertension or ischemic heart disease), signs of worsening of heart failure (in patients with hypertension or ischemic heart disease).

From the nervous system.

Often dizziness * headache *.

Rarely syncope.

For part of the view.

Rarely reduction lacrimation (to consider when wearing contact lenses).

Very rarely, conjunctivitis.

On the part of hearing.

Rare: hearing impairment.

The respiratory system.

Infrequently bronchospasm in patients with asthma or obstructive airways diseases in history.

Rarely allergic rhinitis.

On the part of the digestive tract.

Common: nausea, vomiting, diarrhea, constipation.

Of the skin and connective tissues.

Rarely hypersensitivity reactions, including itching, redness, rash.

Very rarely alopecia. In the treatment of ß-blockers may experience deterioration in patients with psoriasis in the form of psoriatic lesions.

On the part of the musculoskeletal system.

Infrequently, muscle weakness, convulsions.

On the part of the liver.

Rarely hepatitis.

On the part of the circulatory system.

often feeling cold or numbness in the extremities, hypotension (in patients with chronic heart failure patients).

Infrequently, orthostatic hypotension (in patients with chronic heart failure patients), hypotension (in patients with hypertension or ischemic heart disease).

On the part of the reproductive system.

Rare: violation of potency.

Mental disorders .

Infrequently, depression, sleep disturbance.

Rarely nightmares, hallucinations.

Laboratory indicators.

Rare: increased blood triglycerides, increased liver enzymes in the blood plasma (AST, ALT).

Common disorders.

Often, asthenia (patients with chronic heart failure patients), fatigue *.

Infrequently, asthenia (patients with arterial hypertension or ischemic heart disease).

* Applies only to patients with hypertension or ischemic heart disease. These symptoms usually occur early in treatment, are mild and disappear within the first 1-2 weeks.

In case of any side effects or adverse reactions should inform your doctor immediately.

Shelf life

3 years.

Storage conditions

Stored in the original packaging of the reach of children at a temperature not higher than 25 ° C.

Packaging

10 tablets in a blister, 3 or 6 blister packs in a cardboard box.

15 tablets in a blister, 2 or 4 blisters per box.

Category of leave

On prescription.