Composition, form of production and packaging
The tablets covered with a film membrane of light yellow color, cordate, biconcave, with a risk on both sides.
1 tab.
bisoprolol fumarate 5 mg
Excipients: calcium hydrophosphate, anhydrous 132 mg, corn starch, fine powder 14.5 mg, silicon colloidal dioxide, anhydrous 1.5 mg, microcrystalline cellulose 10 mg, crospovidone 5.5 mg, magnesium stearate 1.5 mg.
Composition of the film membrane: hypromellose 2910/15 - 2.2 mg, macrogol 400 - 0.53 mg, dimethicone 100 - 0.11 mg, iron oxide oxide yellow (E172) - 0.02 mg, titanium dioxide (E171) - 0.97 mg.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
25 pcs. - blisters (2) - packs of cardboard.
30 pcs. - blisters (1) - packs of cardboard.
The tablets covered with a film cover of light orange color, cordate, biconcave, with a risk on both sides.
1 tab.
bisoprolol fumarate 10 mg
Excipients: calcium hydrophosphate, anhydrous - 127.5 mg, corn starch, fine powder - 14 mg, silicon colloidal dioxide, anhydrous - 1.5 mg, microcrystalline cellulose - 10 mg, crospovidone - 5.5 mg, magnesium stearate - 1.5 mg.
Composition of the film coat: hypromellose 2910/15 - 2.2 mg, macrogol 400 - 0.53 mg, dimethicone 100 - 0.22 mg, iron dye oxide yellow (E172) - 0.12 mg, ferric iron oxide red (E172) 0.002 mg, titanium dioxide (E171 ) - 0.85 mg.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
25 pcs. - blisters (2) - packs of cardboard.
30 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Selective beta- 1- adrenoblocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.
Has only a slight affinity for? 2- adrenoreceptors of smooth muscles of bronchi and vessels, as well as to? 2- adrenoreceptors involved in the regulation of metabolism.Therefore, bisoprolol in general does not affect the resistance of the respiratory tract and metabolic processes, which are involved? 2- adrenoreceptors.
Selective action of the drug on? 1- adrenoreceptors persists beyond the therapeutic range.
Bisoprolol does not have a pronounced negative inotropic effect.
The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol 1 time / day, its therapeutic effect persists for 24 hours due to the fact that its T 1/2 from the blood plasma is 10-12 hours. Typically, the maximum reduction in blood pressure is achieved 2 weeks after the start of treatment.
Bisoprolol reduces the activity of the sympathoadrenal system by blocking? 1- adrenoreceptors of the heart.
With a single oral intake in patients with IHD without signs of chronic heart failure, bisoprolol reduces heart rate, reduces stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With prolonged therapy, the initially increased OPSS is reduced. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of beta-blockers.
PHARMACOKINETICS
Suction
After oral administration of bisoprolol almost completely (> 90%) is absorbed from the digestive tract. Its bioavailability due to insignificant metabolism at the "first passage" through the liver (at about 10%) is about 90%. Eating does not affect bioavailability. Bisoprolol is characterized by linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the dose range of 5 to 20 mg. C max in blood plasma is achieved in 2-3 hours.
Distribution
Bisoprolol is distributed quite widely. V d is 3.5 l / kg. Binding to plasma proteins reaches about 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. The data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily with CYP3A4 (about 95%), and CYP2D6 plays only a minor role.
Excretion
Bisoprolol clearance is determined by the balance between excretion by the kidneys in an unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites that are also excreted by the kidneys. The total ground clearance is 15 l / h. T 1/2 is 10-12 hours.
Pharmacokinetics in special clinical cases
There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous impairment of liver or kidney function.
INDICATIONS
- arterial hypertension;
- IHD: stable angina;
chronic heart failure.
DOSING MODE
The drug is taken orally 1 time / day. Tablets should be taken 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.
Arterial hypertension and stable angina
The dose is selected individually, primarily taking into account the heart rate and the patient's condition.
As a rule, the initial dose is 5 mg 1 time / day. If necessary, the dose can be increased to 10 mg 1 time / day. In the treatment of hypertension and angina, the maximum recommended dose is 20 mg 1 time / day.
Chronic heart failure
The standard treatment regimen for chronic heart failure includes the use of ACE inhibitors or angiotensin II receptor antagonists (in the case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. At the beginning of the treatment of chronic heart failure with Concor В® it is required to perform a special phase of titration under regular medical supervision.
A prerequisite for treatment with Concor В® is stable chronic heart failure without signs of exacerbation.
Treatment with Concor В® 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.
To ensure the appropriate titration process at the initial stages of treatment, it is recommended to use bisoprolol in the dosage form of a 2.5 mg tablet.
The recommended initial dose is 1.25 mg 1 time / 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 1 time / day. Each subsequent increase in the dose should be carried out at least 2 weeks later. If the increase in the dose of the drug is poorly tolerated by the patient, then a dose reduction is possible.
The maximum recommended dose for the treatment of chronic heart failure is 10 mg 1 time / day.
During titration, regular monitoring of blood pressure, heart rate and degree of symptoms of chronic heart failure is recommended. The worsening of the symptoms of the course of chronic heart failure is possible already from the first day of application of the drug.
If the patient does not tolerate the maximum recommended dose of the drug, then the possibility of a gradual dose reduction should be considered.
During the titration phase or after it, temporary deterioration of the course of chronic heart failure, arterial hypotension or bradycardia is possible. 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 В® 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 for all indications
Treatment with Concor В® is usually long-term.
Special patient groups
Patients with violations of the liver or kidneys of mild or moderate severity , as well as elderly patients, correction of the dosing regimen, as a rule, is not required.
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 done with extreme caution.
Older patients do not need a dose adjustment.
Because There is not enough data on the use of the drug Concor В® in children, it is not recommended to prescribe the drug to children and adolescents under the age of 18 years .
To date, there is insufficient data on the use of Concor В® in patients with chronic heart failure in combination with type 1 diabetes mellitus, expressed kidney 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 chronic heart failure with myocardial infarction during the last 3 months.
SIDE EFFECT
Determination of the frequency of adverse reactions: 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).
From the cardiovascular system: very often - bradycardia (in patients with chronic heart failure); often - exacerbation of symptoms of chronic heart failure (in patients with chronic heart failure), a feeling of cold or numbness in the limbs, a marked decrease in blood pressure (especially in patients with chronic heart failure);infrequent AV conduction, bradycardia (in patients with hypertension or angina pectoris), exacerbation of symptoms of chronic heart failure (in patients with hypertension or angina pectoris), orthostatic hypotension.
From the side of the central nervous system: often - dizziness *, headache *; rarely - loss of consciousness.
From the side of the psyche: infrequently - depression, insomnia; rarely - hallucinations, nightmares.
From the senses: rarely - a decrease in tearing (should be taken into account when wearing contact lenses), hearing impairment; very rarely - conjunctivitis.
On the part of the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or obstructive airway disease in history.
From the side of the digestive system: often - nausea, vomiting, diarrhea, constipation; rarely - hepatitis.
From the laboratory: rarely - an increase in the level of liver enzymes in the blood (AST, ALT).
From the musculoskeletal system: infrequently - muscle weakness, muscle cramps.
From the side of the reproductive system: rarely - a violation of potency.
Allergic reactions: rarely - skin itching, rash, hyperemia of the skin, allergic rhinitis.
From the skin: very rarely - alopecia. Beta-blockers can exacerbate the course of psoriasis or cause a psoriasis-like rash.
Other: often - asthenia (in patients with chronic heart failure), increased fatigue *; infrequently - asthenia (in patients with arterial hypertension or angina pectoris).
* In patients with hypertension or angina pectoris, especially these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.
CONTRAINDICATIONS
- acute heart failure;
- Chronic heart failure in the stage of decompensation, requiring treatment with drugs with a positive inotropic effect;
- cardiogenic shock;
- AV blockade II and III degree, without pacemaker;
- SSSU;
- Sinoatrial blockade;
- pronounced bradycardia (heart rate <60 bpm);
- marked decrease in blood pressure (systolic blood pressure <100 mm Hg);
- severe forms of bronchial asthma and COPD in history;
- marked violations of peripheral arterial blood circulation, Raynaud's disease;
- pheochromocytoma (without simultaneous use of alpha-blockers);
metabolic acidosis;
- age under 18 years (insufficient data on efficiency and safety);
- Hypersensitivity to the components of the drug.
With caution apply the drug with angina Prinzmetal, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, AV-blockade of the first degree, severe renal failure (CC <20 ml / min), expressed violations of the liver function, psoriasis, restrictive cardiomyopathy, congenital heart disease or heart valve disease with severe hemodynamic disorders, chronic heart failure with myocardial infarction during the last 3 months, during the de sensitizing therapy, in patients on a strict diet.
PREGNANCY AND LACTATION
The use of Concor В® during pregnancy is possible only if the intended benefit for the mother is greater than 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 alternative therapeutic measures taken in case of undesirable manifestations in relation to pregnancy or fetus. You should carefully examine the newborn after delivery. In the first 3 days of life, bradycardia and hypoglycemia may occur.
There is no data on the isolation of bisoprolol with breast milk. Acceptance of Concor В® is not recommended for women during lactation. If you need to use the drug during lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function of mild or moderate severity of dosing regimen are generally not required.
For patients with severe renal dysfunction (with a QC less than 20 ml / min), the maximum daily dose is 10 mg.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with impaired liver function of mild or moderate severity of dosing regimen are generally not required.
For patients with severe impairment of liver function, the maximum daily dose is 10 mg.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
Older patients do not need a dose adjustment.
SPECIAL INSTRUCTIONS
The patient should not abruptly discontinue treatment and change the recommended dose without first consulting a doctor, as this can lead to a temporary deterioration in the heart. Treatment should not be interrupted suddenly, especially in patients with ischemic heart disease. If discontinuation of treatment is necessary, the dose should be reduced gradually.
At the initial stage of treatment with Concor В®, patients need constant monitoring of the doctor.
Caution should be used in patients with diabetes mellitus with significant fluctuations in blood glucose (symptoms of severe hypoglycemia, such as tachycardia, palpitations or excessive sweating may be masked), in patients on a strict diet, with desensitizing therapy, AV blockade of the I degree , Prinzmetal angina, violations of peripheral arterial blood flow of mild and moderate degree (at the beginning of therapy there may be an increase in symptoms), with psoriasis (including anamneze).
Respiratory system: with bronchial asthma or COPD, simultaneous application of bronchodilating agents is indicated. In patients with bronchial asthma, an increase in airway resistance may be required, which requires a higher dose of beta 2 -adrenomimetics.
Allergic reactions: beta adrenoblockers, including the Concor В® preparation, can increase sensitivity to allergens and the severity of anaphylactic reactions due to weakening of adrenergic compensatory regulation under the action of beta-adrenoblockers. Epinephrine (epinephrine) therapy does not always produce the expected therapeutic effect.
In the conduct of general anesthesia should take into account the risk of blockade of? -adrenoceptors. If it is necessary to discontinue therapy with Concor В® before surgery, it should be done gradually, and completed 48 hours before general anesthesia. An anesthesiologist should be warned that the patient is taking Concor В® .
In patients with pheochromocytoma, Concor В® can be prescribed only against the background of the use of alpha-blockers.
When treating with Concor В®, symptoms of hyperthyroidism may be masked.
Impact on the ability to drive vehicles and manage mechanisms
Concor В® does not affect the ability to drive vehicles according to the results of the study in patients with IHD. However, due to individual reactions, the ability to drive a car 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.
OVERDOSE
Symptoms: most often - AV blockade, severe 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, in patients with chronic heart failure, sensitivity is high.
Treatment: if an overdose occurs, first of all, stop taking the drug and begin supporting symptomatic therapy.
With pronounced bradycardia - IV injection of atropine. If the effect is insufficient, then with caution, you can introduce 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.
With AV-blockade - constant clinical control, the appointment of beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.
With exacerbation of the course of chronic heart failure - in / in the introduction of diuretics, drugs with a positive inotropic effect, as well as vasodilators.
When bronhospazme - appointment bronhodilatatorov, incl. Beta 2 -adrenomimetikov and / or aminophylline.
When hypoglycemia - in / in a dextrose (glucose).
DRUG INTERACTION
The effectiveness and tolerability of bisoprolol can affect the simultaneous use of other medications. Such interaction may also occur in those cases when the two drugs are taken over a short period of time. The doctor should be informed about the use of other drugs, even if the application is carried out without a prescription.
Deprecated combination
treatment of chronic heart failure,
antiarrhythmic agents of class I (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol can reduce AV-conduction and the contractile ability of the heart.
All indications for use of the drug Concor В®
Calcium channel blockers slow verapamil type and to a lesser extent, diltiazem, while the use of bisoprolol can lead to a decrease of myocardial contractility and AV-conduction disturbance. In particular, on / in the introduction of verapamil in patients receiving beta-blockers may cause severe hypotension and AV-blockade. Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to slowing of the heart rate and reducing cardiac output and vasodilation due to the reduction of the central sympathetic tone. Abrupt withdrawal, particularly before the abolition of beta-blockers may increase the risk of "rebound" hypertension.
Combinations requiring special care
The treatment of hypertension and angina pectoris
antiarrhythmic agents of class I (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while the use of bisoprolol can reduce AV-conduction and contractility of the myocardium.
All indications for use of the drug Konkor В®
blockers slow calcium channels dihydropyridine derivatives (e.g. nifedipine, felodipine, amlodipine) while the application of bisoprolol can increase the risk of hypotension. In patients with chronic heart failure can not eliminate the risk of further deterioration of the contractile function of the heart.
Class III antiarrhythmics (e.g., amiodarone), while the use of bisoprolol can exacerbate violation of AV-conduction.
The action of beta-blockers for topical (e.g., eye drops for treating glaucoma) may enhance the systemic effects of bisoprolol (decrease in blood pressure, heart rate reduction).
Parasympathomimetics while the use of bisoprolol can exacerbate violation of AV-conduction and increase the risk of bradycardia.
When applied simultaneously with the drug Konkor В®possibly increasing hypoglycemic effect of insulin or hypoglycemic agents for oral administration. Symptoms of hypoglycemia, particularly tachycardia, may be masked or suppressed. This interaction is more likely when using non-selective beta-blockers.
General anesthetics can increase the risk cardiodepressive action, leading to hypotension.
Cardiac glycosides while the use of bisoprolol can lead to an increase of the pulse time, and thus, to the development of bradycardia.
NSAIDs may reduce the hypotensive effect of bisoprolol.
Simultaneous application Konkor preparation В®beta-agonists (e.g., isoprenaline, dobutamine) may reduce the effect of both drugs.
Bisoprolol combination with agonists affecting -? -adrenoceptors and (e.g., norepinephrine, epinephrine) may enhance vasoconstrictor effects of these agents due effects on adrenergic receptors, resulting in an increase in blood pressure?. This interaction is more likely when using non-selective beta-blockers.
Antihypertensives, as well as other means with possible antihypertensive effect (e.g., tricyclic antidepressants, barbiturates, phenothiazines) able to enhance the hypotensive effect of bisoprolol.
Mefloquine while the use of bisoprolol can increase the risk of bradycardia.
MAO inhibitors (MAO inhibitors with the exception of B) may enhance the antihypertensive effect of beta-blockers. Concomitant use can also lead to the development of hypertensive crisis.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 5 years.
