Bizomor - instructions for use, dose, side effects, contraindications

The composition of the Winkout WT AQ 01530 dye (yellow) is 100 mg: hypromellose 60.00 mg, macrogol 400 10.02 mg, titanium dioxide 16.62 mg, talc 5.50 mg, macrogol 6000-6.11 mg , aluminum lacquer quinoline yellow - 1.75 mg.

Each tablet, film-coated 5 mg contains:

Active substance: bisoprolol fumarate - 5 mg.

Excipients: mannitol - 146,50 mg, microcrystalline cellulose - 21,10 mg, croscarmellose sodium - 1,80 mg, magnesium stearate - 3,60 mg.

Sheath composition: Winkout WT AQ 01069 (orange) - 3.6 mg.

The composition of the Winkout dye WT-AQ-01069 orange per 100 mg: hypromellose - 61.00 mg, macrogol 400 - 9.50 mg, titanium dioxide - 17.20 mg, talc - 4.77 mg, macrogol 6000 -6.02 mg , aluminum varnish sunset sunset yellow-1.51 mg.

Each tablet, film-coated 10 mg contains:

Active substance: bisoprolol fumarate - 10 mg.

Excipients: mannitol - 141,50 mg, microcrystalline cellulose - 21,10 mg, croscarmellose sodium - 1,80 mg, magnesium stearate - 3,60 mg.

The composition of the coating: dye Winkout WT AQ 01620 (orange) - 3.6 mg.

The composition of the Winkout WT-AQ-01620 orange dye per 100 mg: hypromellose - 60,50 mg, macrogol 400 - 9.50 mg, titanium dioxide - 17.00 mg, talc - 4.50 mg, macrogol 6000 - 6.00 mg , aluminum varnish sunset sunset yellow - 2.50 mg.

Description:

Tablets 2.5 mg: tablets are round, biconvex, covered with a film coating of light yellow color, with a risk on one side. On the fracture, two layers are visible; the core is from white to almost white.

Tablets 5 mg: tablets are round, biconcave, covered with a film shell of light orange color. On the fracture, two layers are visible; the core is from white to almost white.

Tablets 10 mg: tablets are round, biconcave, covered with a film membrane of orange color. On the fracture, two layers are visible; the core is from white to almost white.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:Selective beta-1-adrenoblocker, without its own sympathomimetic activity, does not have a membrane-stabilizing action.
Reduces the activity of renin in the blood plasma, reduces the need for myocardium in oxygen, reduces the heart rate (heart rate).Has antihypertensive, antiarrhythmic and anti-anginal action. Blocking at low doses beta1-adrenoreceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic action (inhibits conduction and excitability, slows down atrioventricular (AV) conductivity). When the dose is increased above the therapeutic dose, beta2-adrenergic blocking action exerts.
The total peripheral vascular resistance at the beginning of the drug application, in the first 24 hours, increases somewhat (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation of beta2-adrenoreceptors), which returns to the initial value after 1-3 days, and decreases with prolonged use.
Antihypertensive effect associated with a decrease in the minute volume of blood, sympathetic stimulation of peripheral vessels, a decrease in the activity of the sympathoadrenal system. (CAS) (is of great importance for patients with initial hypersecretion of renin),restoration of sensitivity in response to lowering blood pressure (BP) and influence on the central nervous system (CNS). With arterial hypertension, the effect occurs after 2-5 days / stable effect - after 1-2 months.
Antianginal action is due to a decrease in myocardial oxygen demand as a result of reduced contractility and other myocardial functions, diastole lengthening, and improved myocardial perfusion. By increasing the end diastolic pressure in the left ventricle and increasing the stretching of ventricular muscle fibers, myocardial oxygen demand may increase, especially in patients with chronic heart failure (CHF).
Antiarrhythmic action is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers, and slowing of AV conduction (mainly in antegrade and, to a lesser extent, in retrograde directions through the AV node) and by additional paths.
When used at average therapeutic doses, in contrast to nonselective beta-blockers, it exerts a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause retention of sodium ions in the body.

Pharmacokinetics:

Suction

Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract (GIT), eating does not affect absorption. Bisoprolol demonstrates linear kinetics, and its concentrations in the blood plasma are proportional to the administered dose in the range of 5 to 20 mg. The maximum concentration of bisoprolol (Cmax) In blood plasma is achieved in 2-3 hours.

Distribution

The volume of distribution (Vd) is 3.5 l / kg. The connection with blood plasma proteins is about 30%.

Metabolism

Metabolized by the oxidative pathway without subsequent conjugation; is slightly metabolized by "primary passage" through the liver (about 10-15%). All metabolites are polar. The main metabolites found in blood plasma and urine, do not show pharmacological activity.The data obtained as a result of experiments with human liver microsomes in vitro, show that bisoprolol is metabolized, first of all, with the participation of the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a small role.

Excretion

Bisoprolol is excreted in two ways, 50% of the dose is metabolized in the liver with the formation of inactive metabolites. About 98% is excreted by the kidneys, 50% of them are unchanged, less than 2% - through the intestines (with bile). The total clearance is 12-18 l / h, and the renal clearance is 8-11 l / h, the half-life (T1 / 2) is 10-12 hours. Permeability through the blood-brain and placental barrier is low. The pharmacokinetics of bisoprolol is linear and does not depend on age. In patients with CHF, the plasma concentration of bisoprolol is higher, and T1 / 2 is longer than in healthy volunteers.

Indications:

- arterial hypertension;

- Ischemic heart disease: prevention of attacks of stable angina pectoris;

- Chronic heart failure (CHF).

Contraindications:

- hypersensitivity to bisoprolol or any of the components, as well as to other beta-blockers;

- acute heart failure;

- CHF in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- collapse;

- AV blockade of II and III degree without an electrocardiostimulator;

- syndrome of weakness of the sinus node;

- Sinoatrial blockade;

- bradycardia (heart rate less than 60 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 100 mm RT.ST.);

- severe bronchial asthma and chronic obstructive pulmonary disease (COPD) in history;

- marked violations of peripheral circulation, Raynaud's syndrome;

- pheochromocytoma (without simultaneous use of alpha-blockers);

metabolic acidosis;

- cardiomegaly (no signs of heart failure);

- simultaneous administration of monoamine oxidase inhibitors (MAO) (with the exception of MAO inhibitors type B);

- concomitant use of floktaphenin and sultopride;

- age under 18 years (efficiency and safety not established).

Carefully:

- bronchial asthma and COPD;

- simultaneous desensitizing therapy;

- Prinzmetal angina;

- hyperthyroidism;

- diabetes;

- AV blockade of the 1st degree;

- marked renal failure (creatinine clearance (CC) less than 20 ml / min);

- pronounced violations of the liver function;

- psoriasis;

- restrictive cardiomyopathy;

- Congenital heart disease or heart valve disease with severe hemodynamic disorders;

- CHF with myocardial infarction during the last 3 months;

- strict diet;

- Depression (including in the anamnesis).

Pregnancy and lactation:In pregnancy, the drug should be recommended for use only if the benefit of treatment for the mother exceeds the risk of side effects in the fetus and / or the child.
As a rule, beta-adrenoblockers reduce blood flow in the placenta and can affect the development of the fetus. The blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored, and in case of appearance of undesirable phenomena in relation to pregnancy and / or fetus, switch to alternative therapies.
In the case of beta-blockers during pregnancy, the newborn should be carefully screened after childbirth. In the first three days of life, bradycardia and hypoglycemia may occur.
Data on the isolation of bisoprolol in breast milk, there is no milk. Therefore, taking BiSemor is not recommended during breastfeeding. If taking the drug during lactation is necessary; Breastfeeding should be discontinued.

Dosing and Administration:Bisomor should be taken orally, with a small amount of liquid in the morning before breakfast, during or after it. Tablets should not be chewed or ground into powder.
In all cases, the regimen is selected by the doctor for each patient individually, in particular taking into account the heart rate and the patient's condition.
Treatment of arterial hypertension and stable angina
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.
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.
For patients with severe renal dysfunction (CC less than 20 ml / min) and patients with severe impairment of liver function, the maximum daily dose is 10 mg.
Chronic heart failure
The beginning of treatment of chronic heart failure requires mandatory carrying out of a special phase of titration and regular medical supervision.A precondition for treatment with BiSemor is stable CHF without signs of exacerbation.
Treatment of chronic heart failure begins as described below, with individual adaptation depending on how well the patient tolerates the prescribed dose, i.е. The dose can be increased only if the previous dose is well tolerated.
The recommended initial dose of the drug Bisomor is 1.25 mg (1/2 tablet 2.5 mg) 1 time / day. Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg, 3.75 mg (VA tablets of 2.5 mg), 5 mg, 7.5 mg (1 tablet of 5 mg glucagon 2.5 mg each) and 10 mg once a day with an interval of at least 2 weeks or more.
The maximum recommended dose of Bisomor in the treatment of chronic heart failure is 10 mg 1 time / day.
If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible.
During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF build-up is recommended. The aggravation of symptoms of CHF is possible from the first day of application of the drug.
During or after the titration phase, temporary deterioration in the course of CHF, arterial hypotension, or bradycardia may occur. In this case, it is recommended, first of all, to pay attention to the choice of the dose of concomitant standard therapy. It may also be necessary to temporarily reduce the dose of Bisomor or to cancel treatment. After stabilization of the patient's condition, a repeated titration of the dose should be performed, or the treatment should be continued.
To date, there is insufficient data on the use of Bisomor in patients with CHF associated with type 1 diabetes mellitus, severe renal and / or liver dysfunction, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant heart disease. Also, until now, there has been insufficient data on patients with CHF with myocardial infarction during the last 3 months.
Duration of treatment for all indications
Treatment is usually lengthy. If necessary, treatment can be interrupted and resumed in accordance with certain rules. 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.

Side effects:

The incidence of adverse reactions described below was determined according to the following classification:

-very often ≥ 1/10;

- Frequently ≥1 / 100, <1/10;

- often ≥ 1/1000, <1/100;

- often> 1/10 000, <1/1000;

-very rare <1/10 000.

From the side of the cardiovascular system

Very often: bradycardia (in patients with CHF).

Often: aggravation of symptoms of CHF flow (in patients with CHF), sensation of cooling or numbness in the extremities, marked decrease in blood pressure, especially in patients with CHF.

Infrequent AV conduction disorder; bradycardia (in patients with hypertension or angina pectoris); aggravation of symptoms of CHF flow (in patients with arterial hypertension or angina pectoris), orthostatic hypotension.

From the side of the central nervous system

Often: dizziness, headache.

Rarely: loss of consciousness.

Mental disorders

Infrequently: depression, insomnia.

Rarely: hallucinations, nightmares.

From the side of the organ of vision

Rarely: decreased lacrimation (should be considered when wearing contact lenses).

Very rarely: conjunctivitis.

From the side of the hearing organ

Rarely: hearing impairment.

From the respiratory system

Infrequent: bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis.

Rarely: allergic rhinitis.

From the digestive system

Often: nausea, vomiting, diarrhea, constipation.

Rarely: hepatitis.

From the side of the musculoskeletal system

Infrequently: muscle weakness, muscle cramps.

From the skin

Rarely: hypersensitivity reactions, such as pruritus, rash, hyperemia of the skin.

Very rarely: alopecia; beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

From the side of the reproductive system

Rarely: a violation of potency.

Common violations

Often: asthenia (in patients with CHF), increased fatigue.

Infrequently: asthenia (in patients with hypertension or angina pectoris).

Laboratory indicators

Rarely: an increase in the concentration of triglycerides and the activity of "hepatic" transaminases in the blood (aspartate aminotransferase and alanine aminotransferase).

In patients with hypertension or angina pectoris, these symptoms often appear at the beginning of the course of treatment,usually are mild in nature and usually pass within 1-2 weeks after the start of treatment.

Overdose:

Symptoms

The most frequent symptoms of overdose: AV blockade, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

The sensitivity to a single intake of a high dose of bisoprolol varies greatly among individual patients and probably patients with CHF have a higher sensitivity.

Treatment

Supportive and symptomatic therapy.
With severe bradycardia: intravenous atropine. If its effect is insufficient, with caution you can introduce a tool that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.
With a marked decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations.
With AV blockade: patients should be under constant supervision, and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.
In acute heart failure: intravenous diuretics, drugs with a positive inotropic effect, as well as vasodilators.
When bronhospazme: the appointment of bronchodilators, incl. beta2-adrenomimetics and / or aminophylline.
When hypoglycemia: intravenous dextrose (glucose).

Interaction:Treatment of CHF
Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.
For all indications
Blockers "slow" calcium channel (BCCI) 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, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.
Hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmeenidin) can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tone.Abrupt cancellation, especially before the abolition of beta-blockers can increase the risk of developing "ricochet" hypertension.
Combinations requiring use with caution
Treatment of arterial hypertension and stable angina.
Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.
For all indications
BCCC derivatives of dihydropyridine (for example, nifedipine, felodipine, amlodipine) may increase the risk of developing arterial hypotension. Patients with CHF can not exclude the risk of subsequent deterioration of the contractile function of the myocardium. Antiarrhythmic drugs of the III class (for example, amiodarone) can enhance the disturbance of AV conduction.
Beta-blockers for topical use (eg, eye drops for the treatment of glaucoma) can exacerbate the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).
Parasympatomimetics with simultaneous application with bisoprolol may increase the disturbance of AV conduction and increase the risk of developing bradycardia.The hypoglycemic effect of insulin or hypoglycemic agents for oral ingestion may be enhanced. Symptoms of hypoglycemia - in particular tachycardia - can be masked, or suppressed. Such interactions are more likely when using nonselective beta-blockers.
Means for general anesthesia can increase the risk of cardiodepressive action, leading to a marked decrease in blood pressure (see section "Special instructions").
Cardiac, glycosides with simultaneous application with bisoprolol can lead to lengthening the time of the pulse, and thus, to the development of bradycardia.
Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of bisoprolol.
The simultaneous use of bisoprolol with beta-adrenomimetics (eg, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenomimetics, affecting beta and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these agents that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure.Such interactions are more likely when using nonselective beta-blockers.
Hypotensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the antihypertensive effect of bisoprolol.
Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.
MAO inhibitors (with the exception of MAO B inhibitors) can enhance the antihypertensive effect of beta-blockers. Simultaneous application can also lead to the development of hypertensive crisis.

Special instructions:Control of patients taking BiSemor should include a measurement of heart rate and blood pressure (at the beginning of treatment - every day, then once every 3-4 months), ECG, blood glucose in patients with diabetes mellitus (1 every 4-5 months). In elderly patients it is recommended to monitor the kidney function (1 time in 4-5 months).
It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 60 beats / min.
Before the start of treatment, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis.
In diabetes mellitus can mask tachycardia caused by hypoglycemia. Unlike nonselective beta-blockers, it does not actually increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.
With the simultaneous administration of clonidine, his reception may be terminated only a few days after the cancellation of the drug Bizomor.
If older bradycardia is detected in elderly patients (less than 60 beats per minute), a decrease in blood pressure (systolic blood pressure below 100 mm Hg), AV blockade, it is necessary to reduce the dose or stop treatment.
It is recommended to stop therapy with the development of depression.
Do not abruptly interrupt treatment because of the risk of developing severe arrhythmias and myocardial infarction. Cancellation of the drug is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days).
At the initial stages of treatment with BiSemor, patients need constant monitoring.
Patients with bronchospastic diseases can be assigned cardioselective beta-blockers in case of intolerance and / or inefficiency of other antihypertensive agents.When the dose of the drug Bisomor exceeds the risk of developing bronchospasm.
It is possible to increase the severity of the reaction of hypersensitivity and the lack of effect from the usual doses of epinephrine against the background of a burdened allergological anamnesis.
Patients who use contact lenses should take into account that against the background of treatment with the drug Bisomore may reduce the production of tear fluid.
When conducting general anesthesia against the background of drug treatment, the risk of blockade of beta-adrenergic receptors should be considered. If it is necessary to discontinue therapy with Bisomor before surgery, the drug is withdrawn gradually, and completed 48 hours before the general anesthesia. If the patient has taken the drug before surgery, he should choose a drug for general anesthesia with a minimum negative inotropic effect. An anesthesiologist should be warned about treatment with BiSemor.
In patients with pheochromocytoma, the drug can be prescribed only against the background of the use of alpha-blockers.
When treated with Biosemar, the symptoms of hyperthyroidism (hyperthyroidism) can be masked (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can strengthen symptoms.
It should be canceled before the study of blood and urine content of catecholamines, normetanephrine and vanillin-mandelic acid, antinuclear antibody titers.
In "smokers" the effectiveness of beta-blockers is lower.

Effect on the ability to drive transp. cf. and fur:During the treatment with Biomore, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Film coated tablets, 2.5 mg, 5 mg and 10 mg.

Packaging:

10 tablets per blister of aluminum foil and PVC film.

For 3 blisters, together with instructions for use, put in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000587

Date of registration:21.09.2011

Expiration Date:21.09.2016

The owner of the registration certificate:Edge Pharma Private LimitedEdge Pharma Private Limited India

Manufacturer: & nbsp

EDGE PHARMA PRIVATE, Limited India

Representation: & nbspEdge Pharma Private Limited Edge Pharma Private Limited India

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Beam (Bisomor)