Expiration date: 02/2025

Release form and composition: 

Tablets, coated light yellow, round, biconvex.

• 1 tablet contains bisoprolol fumarate 5 mg
  

Tablets, film-coated light pink color, round, lenticular, with the mark.

• 1 tablet contains bisoprolol fumarate 10 mg
  

Excipients: microcrystalline cellulose, corn starch, sodium lauryl sulfate, silicon dioxide colloidal anhydrous, magnesium stearate.

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

Pharmacological action:

Selective beta1-blocker without own sympathomimetic activity. Has no membrane stabilizing effect. Reduces plasma renin activity, reduces the need heart of oxygen, reduces the heart rate at rest and during exercise. It has hypotensive, antiarrhythmic and antianginal effects.

Hypotensive effect associated with a decrease in minute volume of blood, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (has a greater significance for patients with initial hypersecretion of renin), restoring sensitivity in response to decreased blood pressure and effects on the Central nervous system. When hypertension hypotensive effect develops after 2-5 days, stable effect - in 1-2 months.

Antianginal effect is due to the reduction of requirement of a myocardium in oxygen as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improved myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of the muscle fibers of the ventricles can increase 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 content, arterial hypertension), reduced rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV conduction (mainly in the antegrade and to a lesser extent, in the retrograde directions through the AV node) and conduction by additional ways. When used in high therapeutic doses, unlike nonselective beta-blockers, has a less pronounced effect on bodies containing beta2-adrenergic receptors (pancreas, skeletal muscle, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause the delay of sodium ions in the body. When used in high doses (200 mg or more) has a blocking effect on both subtypes of beta-adrenergic receptors, primarily in the bronchi and vascular smooth muscle.

Pharmacokinetics:

Suction

Absorption is 80-90%, eating does not affect the absorption. Cmax in plasma is after 1-3 h.

Distribution and metabolism

Linking blood plasma proteins is about 30%. The permeability of the BBB and placental barrier - low, the secretion of breast milk - low. Metabolized in the liver.

Excretion

T1/2 10-12 h. Excreted by the kidneys (50% in unaltered), less than 2% is excreted in the bile.

Indications:

• arterial hypertension
  
• Coronary artery disease: prevention of angina attacks.
  

Dosing regimen:

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

In patients with impaired kidney with QC t 20 ml/min or with acute human liver the maximum daily dose - 10 mg.

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

Side effects:

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

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

From the side of cardiovascular system: sinus bradycardia, palpitations, impaired conductivity infarction, AV-blockade (up to the development of a complete transverse blockade and heart failure), arrhythmia, weakening of myocardial contractility, development (the aggravation of) chronic heart failure (swelling of ankles, feet, shortness of breath), reducing AD, orthostatic hypotension, manifestation of angiospasm (increased peripheral circulatory disorders, cold lower extremities, Raynaud's syndrome), chest pain.

From the digestive system: dry mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, the human liver (dark urine, yellowness of the sclera or skin, cholestasis), changing taste, hepatitis, change in the activity of liver enzymes (ALT, AST), bilirubin, triglycerides.

The respiratory system: nasal congestion, difficulty breathing in the appointment of high doses (loss of selectivity) and/or prone patients - laringo - and bronchospasm.

From the endocrine system: hyperglycemia (in patients with insulin-dependent diabetes mellitus), hypoglycemia (in patients, receiving insulin), hypothyroid state.

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

Dermatological reactions: increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions, exacerbation of psoriasis symptoms.

Allergic reactions: skin itching, rash, hives.

Other: back pain, arthralgia, withdrawal syndrome (increased angina, increased blood pressure), reduced libido, reduced potency.

Contraindications:

• shock (including cardiogenic)
  
• the collapse
  
• pulmonary edema
  
• acute heart failure
  
• chronic cardiac insufficiency of the decompensation
  
• AV blockade II and III degree
  
• sinoatrial block
  
• SSSU
  
• expressed aetiology
  
• angiospasticescoy angina (Prinzmetal's angina)
  
• cardiomegaly (with no signs of heart failure)
  
• hypotension (systolic BP below 100 mm Hg.St., especially in myocardial infarction)
  
• bronchial asthma and chronic obstructive pulmonary disease in anamnesis
  
• simultaneous reception of MAO inhibitors (except for MAO inhibitors of type)
  
• late stage human peripheral blood circulation
  
• Raynaud's disease
  
• pheochromocytoma (without the simultaneous use of alpha-blockers)
  
• metabolic acidosis
  
• the age 18 years (effectiveness and safety have not been established)
  
• hypersensitivity to the medication and other beta-blockers.
  

With caution should designate product in liver failure, chronic renal insufficiency, myasthenia gravis, thyrotoxicosis, diabetes, AV blockade degree I, psoriasis, depression (including in history), elderly patients.

Pregnancy and lactation:

The use of Coronal during pregnancy and lactation (breastfeeding) is possible only 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 retardation, hypoglycemia, bradycardia.

Special instructions:

When assigning Coronal should regularly monitor the HR and AD (at the beginning of treatment - daily, then 1 once in 3-4 mo), conduct an EKG, to determine the level of blood glucose in patients with diabetes mellitus (1 once in 4-5 mo). In elderly patients it is recommended to monitor kidney function (1 once in 4-5 mo).

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

Before treatment is recommended study of respiratory function in patients with a history of broncho-pulmonary history.

Note that about 20% patients with stroke beta-adrenoblokatora ineffective due to severe coronary atherosclerosis with the low threshold of ischemia (heart rate less than 100 beats/min) and increased end diastolic volume of the left ventricle that violate the upper subendocardialnah blood flow.

Smoking patients the effectiveness of beta-blockers reduced.

Patients using contact lenses should take into account that the treatment may decrease the production of tear fluid.

When using Coronal in patients with pheochromocytoma there is a risk of paradoxical hypertension (if not previously achieved effective alpha adrenoblokada).

Bisoprolol may mask certain clinical signs of hyperthyroidism (eg, tachycardia). Sudden removal of the Coronal in patients with thyrotoxicosis is contraindicated, because it can enhance the symptoms of the disease.

Diabetes bisoprolol may mask tachycardia caused by hypoglycemia. Unlike nonselective beta-blockers hardly enhances insulin-induced hypoglycemia and delay recovery of the glucose concentration in the blood to normal levels.

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

Perhaps the increased severity of hypersensitivity reactions and lack of effect of conventional doses of epinephrine (adrenaline) on the background of the burdened allergological anamnesis.

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

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

Medicines, reducing stocks of catecholamines (e.g. reserpine), may enhance the action of beta-adrenoblokatorov, therefore, patients, accepting such combination drugs, should be under constant supervision of a doctor to identify expressed downward AD or bradycardia.

Patients with underlying bronchospastic diseases you can assign a cardioselective blocker in case of intolerance and/or ineffectiveness of other antihypertensive drugs. Overdose is dangerous development of bronchospasm.

In the case of elderly patients increasing bradycardia (less 50 beats/min), expressed lower AD (systolic BP below 100 mm Hg.St.), AV-blockade, it is necessary to reduce the dose or stop the 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. Lifting a gradually reducing the dose for 2 weeks or more (reduce the dose 25% in 3-4 day).

It should stop the drug before the examination of blood and urine catecholamines, metanephrines, vanillymandelic acid, titles of 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 psychomotor speed reactions.

Overdose:

Symptoms: arrhythmia, ventricular arrythmia, expressed aetiology, AV-blockade, reducing AD, heart failure, cyanosis of nails of fingers or palms, difficulty in breathing, bronchospasm, dizziness, fainting, seizures.

Treatment: should be washed stomach and appoint absorbent products. Symptomatic therapy: with advanced AV-blockade - in/in the introduction 1-2 mg of atropine, epinephrine (adrenaline) or staging a temporary pacemaker with ventricular arrhythmia - I/lidocaine (drugs I And class does not apply) if pressure reduction, the patient should be in Trendelenburg position if signs of pulmonary edema - in/in plasma-substituting solutions in case of inefficiency - epinephrine (adrenaline), dopamine, dobutamine (to maintain Chrono - and inotropic action and the elimination of expressed lower AD) in heart failure - cardiac glycosides, diuretics, glucagon in convulsions - in/diazepam with bronchospasm - beta2-agonists 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.

While the use of a Coronal iodine radiopaque drugs for at/in the introduction increases the risk of anaphylactic reactions.

At simultaneous application with phenytoin Coronal for/in the introduction, drugs for inhalation General anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive actions and reduce the likelihood of AD.

While the use of coronal alter the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, the AD).

While the use of Coronal reduces the clearance of lidocaine and xantinov (except difillina) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of Smoking.

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

While the use of a Coronal cardiac glycosides, methyldopa, reserpine, and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or exacerbating bradycardia, AV-blockade, heart failure and heart failure.

While the use of a Coronal nifedipine can lead to significant reduction of AD.

While the use of a Coronal diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive medicines can cause excessive reduction of AD.

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

While the use of a Coronal tricyclic and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and hypnotics drugs increase oppression CNS.

Not recommended simultaneous application of the Coronal with MAO inhibitors because of significant increase gipotenzivnogo actions, break in treatment between receiving MAO inhibitors and Coronal shall be not less than 14 days.

While the use of a Coronal non-hydrogenated ergot alkaloids, ergotamine increases risk of peripheral circulatory disorders.

While the use of a Coronal sulfasalazine bisoprolol improves concentration in plasma.

While the use of a Coronal rifampicin shortens the half-life of bisoprolol.

Terms and conditions of storage:

The drug should be stored in a dark, inaccessible to children place at temperature from 15° to 25°C.