KORONAL

Active material: Bisoprolol
When ATH: C07AB07
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): I10, i20
When CSF: 01.01.01.02
Manufacturer: ZENTIVA a.s. (The Slovak Republic)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, coated light yellow, round, lenticular, with Valium.

Excipients: microcrystalline cellulose, corn starch, sodium lauryl, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, macrogol 400, Titanium dioxide (E171), iron oxide yellow (E172).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.

Pills, coated light pink, round, lenticular, with Valium.

Excipients: microcrystalline cellulose, corn starch, sodium lauryl, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, macrogol 400, Titanium dioxide (E171), iron oxide red (E172).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.

Pharmacological action

Selective beta₁-blocker without its own sympathomimetic activity. It has no membrane stabilizing action. It reduces plasma renin activity, reducing myocardial oxygen demand, It reduces the heart rate at rest and during exercise. It has hypotensive, antiarrhythmic and antianginal.

The antihypertensive action is due to a decrease in cardiac output, sympathetic stimulation of peripheral vascular, decreased activity of the renin-angiotensin system (It is more important for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure and the influence of the central nervous system. When hypertension hypotensive effect develops through 2-5 days, stable effect – through 1-2 Months.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. By increasing the end-diastolic left ventricular pressure and increase the tension of the muscle fibers of the ventricles can be increased oxygen demand, especially in patients with chronic heart failure.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV-conduction (mainly in the antegrade and, less, in retrograde direction through the AV-node) and conductivity for additional ways. When used in high therapeutic doses, Unlike non-selective beta-blockers, It has a less pronounced effect on the organs, содержащие b₂-adrenoreceptory (pancreas, skeletal muscle, smooth muscle peripheral arteries, bronchial and uterine) and carbohydrate metabolism, It does not cause a delay of sodium ions in the body. When used in high doses (200 mg, and more) It exerts a blocking effect on both subtypes of β-adrenoceptor, mainly the bronchi and vascular smooth muscle.

Pharmacokinetics

Absorption

Absorption sostavlyaet 80-90%, meal no effect on absorption. C_max in the blood plasma through 1-3 no.

Distribution and metabolism

Binding to plasma proteins is approximately 30%. The permeability of the BBB and placental barrier – low, the secretion of breast milk – low. It is metabolized in the liver.

Deduction

T_1/2 10-12 no. Report the news (50% – in unchanged form), less 2% excreted in the bile.

Testimony

- Arterial hypertension;

- CHD: prevention of angina attacks.

Dosage regimen

The drug is prescribed inside of 2.5-5 mg 1 time / day. If necessary, increase the dose to 10 mg 1 time / day. The maximum daily dose – 20 mg.

In patients with impaired renal function in QA < 20 ml / min or severe hepatic impairment the maximum daily dose – 10 mg.

Tablets should be taken on an empty stomach in the morning, without chewing.

Side effect

From the central and peripheral nervous system: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesias in extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor.

On the part of the organ of vision: blurred vision, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis.

Cardio-vascular system: sinusovaya bradycardia, heartbeat, conduction disturbances infarction, AV блокада (until the development of a full cross-blockade and heart failure), Arrhythmia, weakening of myocardial contractility, development (aggravation) chronic heart failure (swelling of the ankles, stop, breathlessness), decrease in blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), chest pain.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, abnormal liver function (dark urine, yellow skin or sclera, cholestasis), change in taste, hepatitis, changes in liver enzymes (GOLD, IS), bilirubin, triglycerides.

The respiratory system: nasal congestion, difficulty breathing when administered at high doses (loss of selectivity) and / or in predisposed patients – laringo- and bronchospasm.

On the part of the endocrine system: giperglikemiâ (in patients with non-insulin dependent diabetes mellitus), gipoglikemiâ (patients, receiving insulin), hypothyroid state.

From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

Dermatological reactions: increased sweating, dermahemia, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms.

Allergic reactions: itching, rash, hives.

Other: backache, arthralgia, withdrawal (increasing angina attacks, increased blood pressure), the weakening of the libido, reduced potency.

Contraindications

- Shock (incl. cardiogenic);

- Collapse;

- Pulmonary edema;

- Acute heart failure;

- Chronic heart failure decompensation;

— AV-blockade II and III degrees;

- Sinoatrialynaya blockade;

- SSS;

- Vыrazhennaya bradycardia;

- Angiospastic angina (Prinzmetal angina);

- Kardiomegalija (without signs of heart failure);

- Hypotension (systolic BP below 100 mmHg., especially in myocardial infarction);

- Asthma and chronic obstructive pulmonary disease in history;

- Simultaneous MAO inhibitors (except the MAO-B inhibitor);

- Late stages of peripheral circulatory disorders;

- Raynaud's disease;

- Pheochromocytoma (without the simultaneous use of alpha-blockers);

- Metabolic acidosis;

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to the medication and other beta-blockers.

FROM caution should be prescribed the drug for liver failure, chronic renal failure, myasthenia, thyrotoxicosis, diabetes, AV-blockade I degree, psoriaze, depression (incl. history), elderly patients.

Pregnancy and lactation

Coronal Application during pregnancy and lactation (breast-feeding) possible if, if the expected benefit to the mother outweighs the risk of side effects in the fetus or child.

When receiving bisoprolol during pregnancy the fetus is possible intrauterine growth, gipoglikemiâ, bradycardia.

Cautions

In appointing Coronal should regularly monitor the heart rate and blood pressure (at the beginning of treatment – daily, then – 1 once every 3-4 Months), conduct an electrocardiogram, determine the level of blood glucose in patients with diabetes (1 once every 4-5 Months). In elderly patients, it is recommended to monitor renal function (1 once every 4-5 Months).

It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 u. / min.

Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.

It should be taken into account, that approximately 20% angina patients beta-blockers are ineffective because of severe coronary atherosclerosis with a low threshold of ischemia (HR less 100 u. / min) and increased end-diastolic volume of the left ventricle, violates the subendocardial blood flow.

At smoking patients the effectiveness of beta-blockers reduced.

Sick, use contact lenses, We should take into account, that against the background of treatment may decrease the production of tear fluid.

When using the Coronal in patients with pheochromocytoma has the paradoxical risk of hypertension (if not previously achieved effective alpha adrenoblockade).

Bisoprolol may mask certain clinical signs of hyperthyroidism (eg, taxikardiju). Abrupt withdrawal Coronal in patients with thyrotoxicosis is contraindicated, Since the ability to strengthen the symptoms of the disease.

In diabetes Bisoprolol may mask tachycardia, induced hypoglycemia. In contrast, non-selective beta blockers hardly increase insulin-induced hypoglycemia or delay recovery of the concentration of glucose in the blood to normal levels.

At the same time taking clonidine its reception can be terminated only after a few days after discontinuation of bisoprolol.

Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine (adrenaline) with aggravated allergic history.

In the case of the need for a planned surgical treatment is carried out for the abolition of the drug 48 h before general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate I / atropine (1-2 mg).

Drugs, reducing stocks catecholamines (incl. reserpine), may enhance the action of beta-blockers, so patients, taking such drug combinations, We should be under constant medical supervision to identify pronounced reduction in blood pressure or bradycardia.

Patients with concomitant diseases bronhospasticheskimi can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs. Overdose danger of developing bronchospasm.

In the case of elderly patients increasing bradycardia (less 50 u. / min), significant decrease in blood pressure (systolic BP below 100 mmHg.), AV-blockade is necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy in the development of depression.

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. The abolition of a gradually, reducing the dose for 2 weeks or more (reduce the dose to 25% in 3-4 day).

It should stop the drug before the study content in the blood and urine catecholamines, metanephrines, vanilinmindalnoy acid, antinuclear antibodies.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: arrhythmia, ventricular premature beats, vыrazhennaya bradycardia, AV блокада, decrease in blood pressure, heart failure, cyanosis of nails of fingers or hands, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: you need to wash the stomach and assign absorbent products. Symptomatic therapy: at razvivšejsâ AV-blockade – in / introduction 1-2 mg atropine, epinephrine (adrenaline) or setting a temporary pacemaker; when ventricular arrhythmia – w / w lidocaine (A class of drugs I do not apply); decrease in blood pressure when the patient should be in the Trendelenburg position; in the absence of symptoms of pulmonary edema – I / O solutions plazmozameschayuschie, the ineffectiveness – administration of epinephrine (adrenaline), dopamine, doʙutamina (to maintain chrono- and inotropic effects and eliminate significant decrease in blood pressure); Heart failure – cardiac glycosides, Diuretic, glucagon; with cramps – in / diazepam; with bronchospasm – beta₂-agonists by inhalation.

Drug Interactions

Allergens, used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients, receiving bisoprolol.

In an application with the Coronal iodine radiopaque drugs for i / v administration increase the risk of anaphylactic reactions.

In an application with the Coronal phenytoin for / in the, drugs for inhalation general anesthesia (hydrocarbon derivatives) cardiodepressive increase the severity of the action and the probability of reduction of blood pressure.

In an application Coronal alter the effectiveness of insulin and oral hypoglycemic drugs, masking the symptoms of developing hypoglycemia (taxikardiju, increased blood pressure).

In an application Coronal reduces the clearance of lidocaine and xanthine (except difillina) and increases their concentration in the plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

NSAIDs (due to the delay of sodium ions and the blockade of prostaglandin synthesis by the kidneys), SCS and estrogens (by delaying the sodium ions) weaken hypotensive effect Coronal.

In an application with cardiac glycosides Coronal, methyldopa, reserpine and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening of bradycardia, AV-blockade, heart failure and congestive heart failure.

In an application with the Coronal nifedipine may lead to a significant reduction in blood pressure.

In an application with the Coronal diuretics, klonidin, simpatolitiki, hydralazine, and other antihypertensive drugs may cause an excessive decrease of blood pressure.

Coronal prolongs the action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin.

In an application with the Coronal tricyclic antidepressants and tetracyclic, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics drugs increase CNS depression.

Not recommended simultaneous application Coronal with MAO inhibitors due to a significant increase in the hypotensive action, a break in treatment between the reception of MAO inhibitors and Coronal must be at least 14 days.

In an application with the Coronal non-hydrogenated ergot alkaloids, ergotamine increase the risk of peripheral circulatory disorders.

In an application with the Coronal sulfasalazine increases the concentration of bisoprolol plasma.

In an application with rifampicin Coronal shortens the half-life of bisoprolol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in the dark, inaccessible to children at temperature from 15 ° to 25 ° C. Shelf life – 2 year.