It reduces the activity of renin in blood plasma, reduces myocardial oxygen demand, slows buy sustanon 250 the heart rate (HR). It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses beta1- adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), decreases intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effect (inhibits the conductivity buy sustanon 250 and excitability slows atrioventricular (AV) conduction). With increasing doses of the above \ blocking effect.
The antihypertensive effect is associated with a decrease in cardiac output, peripheral vascular sympathetic stimulation, decreased activity simpatoadrenalovoj system. (NAC) (important for patients with baseline renin hypersecretion), sensitivity in response to restoration of blood pressure reduction (BP) and the influence on the central nervous system (CNS). When hypertension effect occurs within 2-5 days, stable operation – through 1-2 months.
Antianginal effect is due to a decrease in myocardial oxygen demand by reducing contractility and other functions of the myocardium, lengthening diastole, improving myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of the muscle fibers of the ventricles may increase myocardial oxygen demand, especially in patients with chronic heart failure (CHF).
Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP levels, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing AV-conduction (primarily in the antegrade and to a lesser extent, in a retrograde direction through the AV node) and on additional routes.
When used in high therapeutic doses, unlike non-selective beta-blocker, has a less pronounced effect on organs comprising a beta2-adrenoceptor (pancreas, skeletal muscle, smooth muscle of peripheral arteries, bronchial and uterine) and carbohydrate metabolism, does not cause delays sodium ions in the body.
The absorption of
bisoprolol almost completely (> 90%) is absorbed from the gastrointestinal tract (GIT), food intake has no effect on absorption. Bisoprolol demonstrates linear kinetics, and its plasma concentration is proportional to the dose administered in the range of 5 to 20 mg. The maximum concentration of bisoprolol (C max ) in plasma is achieved in 2-3 hours.
The volume of distribution (Vd) is 3.5 l / kg. Communication with plasma proteins – about 30%.
is metabolized by oxidative way without further conjugation; slightly metabolized at “primary pass” through the liver (approximately 10-15%). All polar metabolites. Major metabolites detected in plasma and urine did not exhibit pharmacological activity. Data obtained from experiments with microsomes in vitro human liver demonstrate that bisoprolol is metabolized, primarily involving isoenzyme CYP3A4 (about 95%) and CYP2D6 isozyme plays only a small role.
bisoprolol displayed in two ways, 50% of the dose is metabolized in the liver to inactive metabolites. About 98% is excreted by the kidneys, of which 50% – unchanged, less than 2% – through the intestines (in the bile). The total clearance is 12-18 l / h and the renal clearance is 8-11 liters / hour, the half-life (T1 / 2) – 10-12 hours The permeability of the blood-brain barrier and the placental low.. Pharmacokinetics bisoprolol linear and independent of age. In patients with CHF bisoprolol plasma concentrations above, and T1 / 2 is longer than in healthy volunteers
Indications for use:
- arterial hypertension;
- Coronary heart disease: prevention of attacks of stable angina;
- Chronic heart failure (CHF).
Contraindications for use:
- hypersensitivity to bisoprolol or to any of the components, as well as to other beta-blockers;
- congestive heart failure;
- Heart failure decompensation requiring of inotropic therapy;
- cardiogenic shock;
- AV blockade II and III level without pacemaker;
- sick sinus syndrome;
- sinoatrial block;
- bradycardia (heart rate less than 60 beats / min);
- severe hypotension (systolic blood pressure less than 100 mm Hg);
- severe bronchial asthma and chronic obstructive pulmonary disease (COPD) in history;
- expressed by peripheral circulatory disorders, Raynaud’s syndrome;
- pheochromocytoma (without the simultaneous use of alpha-blockers);
- metabolic acidosis;
- cardiomegaly (without heart failure);
- simultaneous reception of monoamine oxidase inhibitors (MAOIs) (except MAO-B inhibitors);
- concomitant use floctafenine and sultopride;
- age of 18 years (effectiveness and safety have been established).
- asthma and COPD
- simultaneous desensitizing therapy;
- Prinzmetal angina;
- AV block of I degree;
- severe renal impairment (creatinine clearance (CC) of less than 20 ml / min);
- expressed human liver;
- kardiomiopitiya restrictive;
- congenital heart defect or heart valve with severe hemodynamic impairment;
- CHF with myocardial infarction within the last 3 months;
- strict diet;
- depression (including history).
Pregnancy and lactation
In pregnancy, the drug should be recommended for use only in the event that the treatment benefit to the mother outweighs the risk of side effects in the fetus and / or the child.
Typically, beta-blockers decrease the blood flow in the placenta and can affect fetal development. blood flow should be controlled in the uterus and placenta, and to observe the growth and development of the child and in the event of adverse events in respect of pregnancy and / or fetal switch to alternative therapies.
In the case of beta-blockers during pregnancy should be carefully examine the newborn after delivery. In the first three days of life may ‘occur symptoms of hypoglycemia and bradycardia.
Data on the allocation of bisoprolol into breast milk is not. Therefore reception Bisomor drug is not recommended during lactation. If administration during lactation is necessary, breast-feeding should be discontinued.
Dosing and Administration
Bisomor The drug, taken orally, drinking – a small amount of liquid in the morning before breakfast, during or after it. Tablets should not chew or rub in powder.
In all cases, the mode of reception and dose chooses doctor for each patient individually, in particular taking into account the patient’s heart rate and the state
Treatment of hypertension and stable angina
Typically, the initial dose is 5 mg 1 time / day. If necessary, the dose may be increased to 10 mg 1 time / day.
In the treatment of hypertension and angina pectoris the maximum recommended dose is 20 mg 1 time / day.
Patients with impaired hepatic or renal function, mild or moderate severity, as well as elderly patients correct dosing regimen is usually not required.
For patients with severe renal impairment (creatinine clearance less than 20 ml / min) and in patients with severely impaired hepatic function, the maximum daily dose is 10mg.
Chronic heart failure
Initiation of treatment of chronic heart failure requires a mandatory holding a special titration phase and regular medical supervision. A prerequisite of treatment Bisomor is stable chronic heart failure without acute symptoms.
Treatment of chronic heart failure starts in accordance with the scheme shown below, wherein individual adaptation may be required depending on how well the patient carries the prescribed dose, i.e. the dose can be increased only if the previous dose was well tolerated.
The recommended initial dose of the drug Bisomor is 1.25 mg (1/2 a tablet 2.5 mg) 1 times / LPG. Depending on individual tolerance dose should be gradually increased to 2.5 mg, 3.75 mg (11/ 2 tablets of 2.5 mg), 5 mg, 7.5 mg (1 tablet of 5 mg tablet 2.5 mg ) and 10 mg once a day with an interval of at least 2 weeks or more.
The maximum recommended dose Bisomor drug in the treatment of chronic heart failure is 10 mg 1 time / day.
If an increase in the dose of the drug is poorly tolerated by the patient, the dose may be reduced.
During the titration is recommended regular monitoring. Blood pressure, heart rate and increase of CHF symptoms. Worsening heart failure symptoms may already be on the first day of the drug.
During the titration phase, or it can occur after a temporary deterioration in the current CHF, hypotension or bradycardia. In this case, it is recommended, above all, pay attention to the selection of a dose of concomitant standard therapy. It may also require temporary dose reduction or withdrawal of treatment Bisomor. After stabilization, the patient should undertake a re-titration of the dose or continue the treatment.
There are currently insufficient data on the use of the drug Bisomor in patients with CHF, conjugated with type 1 diabetes, severe impaired renal function and / or liver disease, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant heart disease. Also still not enough data was received with respect to CHF patients with myocardial infarction within the past 3 months.
Duration of treatment poi all indications
Treatment is usually lengthy. If necessary, treatment can be interrupted and resumed with the observance of certain rules. Treatment should not be interrupted suddenly, especially in patients with CAD. If you want to discontinuation of treatment, the dose should be reduced gradually.
The frequency of adverse reactions listed below was determined according to the following classification:
-very often ≥ 1/10;
-Frequently ≥1 / 100, <1/10;
-nechasto ≥ 000 1/1, <1/100;
-rare ≥ 1/10 000, <1/1000,
Very rare < 1.10 000
Very common:. Bradycardia (in patients with heart failure)
Common: worsening of heart failure flow of symptoms (patients with CHF), feeling cold weather or numbness in the extremities, marked reduction in blood pressure, especially in patients with CHF.
Uncommon: violation AV conduction; bradycardia (in patients with hypertension or angina pectoris); worsening symptoms of heart failure flow (in patients with hypertension or angina), orthostatic hypotension.
On the part of the central nervous system
Common: dizziness *, headache *.
Rare: loss of consciousness.
Uncommon: depression, insomnia.
Rare: hallucinations, nightmares.
On the part of the organ of vision
Rare: decrease in lacrimation (to consider when wearing contact lenses).
Very rare; conjunctivitis.
On the part of the organ of hearing
Rare: hearing impairment.
The respiratory system
Uncommon:. Bronchospasm in patients with asthma or airway obstruction history
Rare: allergic rhinitis.
From the digestive system.
Often: nausea, vomiting, diarrhea, constipation.
On the part of the musculoskeletal system
Uncommon: muscle weakness, muscle cramps.
For the skin
Rare: hypersensitivity reactions such as pruritus, rash, flushing of the skin.
Very rare: alopecia; Beta-blockers may exacerbate the symptoms of psoriasis flow or induce psoriasis-like rash.
Rare: impaired potency.
Common: asthenia (patients with chronic heart failure), fatigue *.
Uncommon: asthenia (patients with hypertension or angina).
Rare: increase in triglyceride concentration and activity of “liver” transaminases in the blood (alanine aminotransferase and aspartate aminotransferase).
The most common symptoms of overdose: AV block, bradycardia, marked reduction in blood pressure, bronchospasm, acute cardiac insufficiency and hypoglycaemia.
Sensitivity to single receiving high doses of bisoprolol varies greatly among individual patients and probably patients with CHF have a higher sensitivity.
Supportive and symptomatic therapy.
In severe bradycardia: atropine intravenous administration. If its effect is insufficient, you can enter with caution agent with positive chronotropic effect. Sometimes it may require temporary staging an artificial pacemaker.
In marked decrease in blood pressure: intravenous fluids and plasma-vasopressor drugs.
When AV blockade: patients should be under constant supervision and be treated with beta-agonists such as epinephrine. If necessary – setting an artificial pacemaker.
In acute heart failure: intravenous diuretics, drugs with positive inotropic effect and vasodilators.
When bronchospasm: the appointment of bronchodilators, including beta2-agonists and / or aminophylline.
When hypoglycemia: intravenous dextrose (glucose).
Interaction with other drugs
Not recommended combinations
Treatment of heart failure
class I antiarrhythmics. (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.
For all indications
blockers “slow” calcium channels (BCCI) verapamil type and to a lesser extent, diltiazem, while the use of bisoprolol may lead to a decrease in myocardial contractility and AV conduction disorders. In particular, intravenous administration of verapamil in patients receiving beta-blockers may cause severe hypotension and AV blockade.
Antihypertensive, centrally acting agents (such as clonidine, methyldopa, moxonidine, rilmenidine) may lead to a slowing of the heart rate and reducing cardiac output and to vasodilatation 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 the use with caution
Treatment of hypertension and stable angina.
Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.
For all indications
BCCI dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine) may increase the risk of hypotension. In patients with heart failure can not eliminate the risk of further deterioration of myocardial contractile function. Class III antiarrhythmics (eg, amiodarone) may increase the violation of AV conduction.
Beta-blockers for topical application (eg eye drops for glaucoma treatment) may increase the systemic effects of bisoprolol (lowering blood pressure, slowing of the heart rate).
Parasympathomimetics while the use of bisoprolol may increase the violation of AV conduction and increase the risk of bradycardia.
Hypoglycemic effect of insulin or hypoglycemic agents for oral administration can be enhanced. Symptoms of hypoglycaemia – particularly tachycardia – may be masked or suppressed. Such interactions are more likely when using non-selective beta-blockers.
Funds for general anesthesia may increase the risk cardiodepressive action, leading to a marked decrease in blood pressure (see. “Special Instructions” section)
Cardiac glycosides while the use of bisoprolol may lead to a lengthening of the time of the pulse, and thus, to the development of bradycardia.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect of bisoprolol.
The simultaneous use of bisoprolol with beta-adrenergic agonists (e.g., isoprenaline, dobutamine) may reduce the effects of both drugs.
Bisoprolol combination with agonists affecting the beta- and alpha-adrenergic receptors (such as norepinephrine, epinephrine) can amplify the effects of vasoconstrictor agents encountered with alpha-adrenoceptors, leading to increased blood pressure. Such interactions are more likely when using non-selective beta-blockers.
Antihypertensives, as well as with other possible means antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may enhance the antihypertensive effect of bisoprolol.
Mefloquine while the use of bisoprolol may increase the risk of bradycardia.
MAO inhibitors (except MAO inhibitors) may increase the antihypertensive effect of beta-blockers. Concomitant use can also lead to the development of hypertensive crisis.
Monitoring of patients taking the drug Bisomor should include measurement of heart rate and blood pressure (at the beginning of treatment – daily, then 1 every 3-4 months) holding an electrocardiogram, determination of blood glucose levels in diabetic patients (1 every 4-5 mo.). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months.).
It is necessary to train the patient’s heart rate calculation method and instruct on the need of medical advice in heart rate less than 60 beats / min.
Before treatment is recommended to study of respiratory function in patients with a history of bronchopulmonary history.
In diabetes may mask tachycardia caused by hypoglycemia. In contrast, non-selective beta-blockers is not practically increase insulin-induced hypoglycemia or delay recovery of blood glucose to normal levels.
At the same time taking clonidine its reception can be terminated only after a few days after discontinuation of the drug Bisomor.
In the case of elderly patients increasing bradycardia (less than 60 beats / min), pronounced reduction in blood pressure (systolic blood pressure below 100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue 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. Abolition of the drug was gradually reducing the dose for 2 weeks or more (reduce dose by 25% in 3-4 days).
In the initial stages of treatment Bisomor patients need constant monitoring.
Patients with diseases bronhospasticheskimi can assign cardioselective beta-blockers in the case of intolerance and / or ineffectiveness of other antihypertensive agents. In excess doses of medication Bisomor there is a risk of bronchospasm.
Perhaps the increased severity of hypersensitivity reactions and the lack of effect of conventional doses of epinephrine with aggravated allergic history.
Patients who use contact lenses, it should be noted that against the background of treatment with Bisomor may decrease production of tear fluid.
When general anesthesia on a background of drug treatment should take into account the risk of blockade of beta-adrenergic receptors. If necessary, termination of therapy with Bisomor before surgery, the removal of the drug was gradually and was completed within 48 hours prior to general anesthesia. If the patient has taken the drug before surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect. It is necessary to warn the anesthetist on the treatment of drug Bisomor.
In patients with pheochromocytoma drug can only be assigned to treatment with alpha-blockers.
In the treatment of drug Bisomor symptoms of hyperthyroidism (hyperthyroidism) may be masked (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because the symptoms can increase.
It is necessary to cancel prior to the study in blood and urine catecholamines and Normetanephrine vanilinmindalnoy acid, antinuclear antibody titers.
The “smoking” the effectiveness of beta-blockers lower.
Effects on ability to drive vehicles and other complex mechanical means:
the period of treatment Bisomor must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
Tablets, film-coated, 2.5 mg, 5 mg and 10 mg.
10 tablets in blister foil PVC and aluminum foil.
3 blisters with instruction on use are placed in a stack of cardboard.