Instruction for use: Byol

Trade name of the drug – Byol

Dosage Form: tablets

Active substance: Bisoprololum

ATX

C07AB07 bisoprolol

Pharmacotherapeutic group: Beta1-selective blocker [Beta-blockers]

The nosological classification (ICD-10)

I10 Essential (primary) hypertension: hypertension; Arterial hypertension; Arterial hypertension crisis course; Essential Hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Primary hypertension; Arterial hypertension, complications of diabetes; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; arterial Hypertension; malignant Hypertension; Hypertonic disease; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; Isolated systolic hypertension

I15 Secondary hypertension: Arterial hypertension, complications of diabetes; hypertension; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; hypertension; arterial Hypertension; malignant Hypertension; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; hypertension; Arterial hypertension; Arterial hypertension crisis course; renovascular hypertension; Hypertension symptomatic; Renal hypertension; Renovascular hypertension; renovascular hypertension; Symptomatic hypertension

I20 Angina [angina]: Heberden disease; Angina pectoris; The attack of angina pectoris; recurrent angina; Spontaneous angina; Stable angina pectoris; Angina rest; Angina progressing; Angina mixed; Angina spontaneous; stable angina; Chronic stable angina; Angina Syndrome X

I25 Chronic ischemic heart disease: Coronary heart disease on the background of hypercholesterolemia; Coronary heart disease is a chronic; Coronary heart disease; Stable coronary artery disease; Percutaneous transluminal angioplasty; Myocardial ischemia, arteriosclerosis; Recurrent myocardial ischemia

I50.0 Congestive heart failure: anasarca heart; Decompensated congestive heart failure; Congestive heart failure; Congestive heart failure with high afterload; Congestive chronic heart failure; Cardiomyopathy with severe chronic heart failure; Compensated chronic heart failure; Swelling with circulatory failure; Edema of cardiac origin; Swelling of the heart; Edematous syndrome in diseases of the heart; Edematous syndrome in congestive heart failure; Edematous syndrome in heart failure; Edematous syndrome in heart failure or liver cirrhosis; right ventricular failure; Congestive Heart Failure; Heart failure stagnant; Heart failure with low cardiac output; Heart failure is a chronic; Cardiac edema; Chronic decompensated heart failure; Chronic Congestive Heart Failure; Chronic heart failure; Change of liver function in heart failure

Composition (per tablet):

active substance: bisoprolol hemifumarate 5 mg; 10 mg

Excipients: MCC - 20/40 mg; calcium hydrogen phosphate - 51.8 / 103.6 mg; corn starch - 5/10 mg; croscarmellose sodium - 1.7 / 3.4 mg; magnesium stearate - 0.75 / 1.5 mg; Colloidal anhydrous silica - 0.75 / 1.5 mg

shell film: lactose monohydrate - 1.24 / 2.48 mg; Valium - 0.96 / 1.92 mg; titanium dioxide - 0.9 / 1.8 mg; macrogol 4000 - 0.34 / 0.68 mg; dye iron (III) oxide, yellow - 0.06 / 0.12 mg; dye iron (III) oxide red - - / 0.002 mg

Description

Tablets, film-coated, 5 mg: Light yellow, round, biconvex, with cross mark on one side and engraved with «BIS 5" - on the other, on a break - white.

Tablets, film-coated, 10 mg: yellow, round, biconvex, with cross mark on one side and engraved with «BIS 10" - on the other, on a break - white.

Characteristic

Selective β1-blocker.

Pharmacological Properties of Byol

Pharmachologic effect - antianginal, hypotensive, beta-adrenoceptor blocking.

Pharmacodynamics

Selective β1-blocker, without its own sympathomimetic activity, has no membrane stabilizing action. It has only a negligible affinity for the β2-adrenoceptor bronchial smooth muscle and blood vessels, as well as the β2-adrenergic receptors, involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect the airway resistance and metabolic processes that are involved in the β2-adrenergic receptors.

Blocking in low doses of beta1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, inhibits all functions of the heart, reduces AV conduction and excitability. If you exceed the therapeutic dose has beta2-adrenoceptor blocking action. PR at the beginning of the drug in the first 24 hours, is increased (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of beta2-adrenoceptor), after 1-3 days returned to the initial value, and long-term use - is reduced. The antihypertensive effect is associated with a decrease in cardiac output, peripheral vascular sympathetic stimulation, decreased activity simpatoadrenalovoj system (SAS) (is of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to the decrease in blood pressure and effect on the central nervous system. When hypertension effect develops after 2-5 days, stable operation is noted after 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 can increase oxygen demand, especially in patients with CHF.

For a single ingestion in patients with coronary artery disease with no evidence of heart failure bisoprolol slows heart rate, reduces the stroke volume and, as a consequence, reduces the ejection fraction and myocardial oxygen demand. When long-term therapy initially elevated peripheral vascular resistance is reduced. Reducing the activity of renin in blood plasma is considered as one of the components of the antihypertensive action of β-blockers.

Pharmacokinetics

Bisoprolol almost completely absorbed from the gastrointestinal tract, food intake does not affect absorption. Bioavailability - about 90%.

Tmax is 2-4 hours after ingestion. Binding to plasma proteins - 26-33%. It is metabolized in the liver metabolites bisoprolol not possess pharmacological activity. T1 / 2 is 9-12 hours, which makes possible the application of drug 1 time per day.

Excreted by the kidneys - 50% in an unmodified form, less than 2% - through the intestines.

The permeability of the BBB and placental barrier - low, in small amounts excreted in breast milk.

Indications for Byol

chronic heart failure;

arterial hypertension;

Coronary heart disease - prevention of attacks of stable angina.

Contraindications for Byol

hypersensitivity to bisoprolol or to any of the excipients and other β-blockers;

lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

cardiogenic shock;

collapse;

congestive heart failure;

Chronic heart failure decompensation requiring of inotropic therapy;

AV blockade II and III level without pacemaker;

sinoatrial block;

syndrome sick sinus;

bradycardia (heart rate less than 50 beats / min.);

severe bronchial asthma or chronic obstructive pulmonary disease;

marked reduction of blood pressure (SBP less than 90 mm Hg..);

The expressed disturbances of peripheral circulation or Raynaud's syndrome;

pheochromocytoma (without the simultaneous use of α-blockers);

metabolic acidosis;

lactation;

simultaneous MAO inhibitors (except for MAO-B inhibitors);

age of 18 years (effectiveness and safety have been established).

Precautions: conducting desensitizing therapy; Prinzmetal angina; hyperthyroidism; diabetes type 1 and diabetes with considerable fluctuations in blood glucose concentration; AV block of I degree; severe renal failure (Cl creatinine less than 20 ml / min); expressed human liver; psoriasis; restrictive cardiomyopathy; congenital heart defect or heart valve with severe hemodynamic impairment; chronic heart failure, myocardial infarction within the last 3 months; pheochromocytoma (with concomitant use of alpha-blockers); strict diet.

Pregnancy and breast-feeding

Bisoprolol has no direct cytotoxic, mutagenic and teratogenic effects, but has pharmacological effects that may cause harmful effects on pregnancy and / or the fetus or newborn. Typically, beta-blockers reduce placental perfusion, which leads to a slowing of fetal growth, fetal death, miscarriage or premature birth. In the fetus and newborn child may have abnormal reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.

Biol® The drug should not be used during pregnancy, the use is possible in the case if the benefit to the mother outweighs the risk of side effects in the fetus and / or the child. In the case where treatment with Biol® regarded as necessary, should monitor blood flow in the placenta and uterus, and also to observe the growth and development of the child and in the event of adverse events in respect of pregnancy and / or fetus, the use of alternative therapies. It is necessary to carefully examine the newborn after delivery. Symptoms of hypoglycaemia and bradycardia tend to occur during the first three days of life.

The period of breastfeeding. Data on the penetration of bisoprolol into breast milk is not. Therefore, use of the drug Biol® not recommended for women during lactation.

If necessary, use during lactation should stop breastfeeding.

Side effect of Byol

The frequency of adverse reactions listed below is defined as follows (the WHO classification): very often - at least 10%; often - at least 1% but less than 10%; infrequently - at least 0.1% but less than 1%; rare - less than 0.01% but less than 0.1%; very rarely - less than 0.01%, including isolated reports.

From the CCC: very often - slowing the heart rate (bradycardia, particularly in patients with CHF), palpitations; often - marked reduction of blood pressure (especially in patients with CHF), a manifestation of vasoconstriction (increased peripheral circulatory disorders, feeling of cold in the extremities (paraesthesia); rarely - a violation of AV conduction (until the development of a complete transverse blockade and heart failure), arrhythmia, orthostatic hypotension , worsening of heart failure with the current development of peripheral edema (swelling of the ankles, feet, shortness of breath), chest pain.

From the nervous system: often - dizziness, headache, asthenia, fatigue, sleep disturbances, depression, anxiety; rare - confusion, or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremor, muscle cramps. Generally, these effects are mild and are usually within 1-2 weeks after starting treatment.

From the sensory organs: rarely - visual disturbances, reduced lacrimation (to consider when wearing contact lenses), tinnitus, hearing loss, ear pain; very rare - dryness and soreness of the eyes, conjunctivitis, taste disturbance.

With the respiratory system: rarely - bronchospasm in patients with asthma or obstructive airways disease; rarely - allergic rhinitis; nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, stomach pain; rarely - hepatitis, elevated liver enzymes (ALT, AST), increased bilirubin concentration, change in taste.

From the musculoskeletal system: rarely - arthralgia, back pain.

From the urogenital system: very rarely - a violation of potency, libido weakening.

Laboratory findings: rarely - increased concentration of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rarely - itching, rash, urticaria.

For the skin: rarely - increased sweating, flushing of the skin, rash, psoriasiform skin reactions; very rare - alopecia; Beta-blockers may exacerbate psoriasis.

Other: withdrawal syndrome (increased frequency of angina attacks, increased blood pressure).

Interaction

On the efficacy and tolerability of the bisoprolol may affect concomitant use of other drugs. Such interaction may also occur in those cases when the two drugs taken after a short time. The doctor should be informed about taking other medicines, even if they are received without a doctor's prescription (ie, non-prescription drugs).

Not recommended combinations

Class I antiarrhythmics (eg quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), while the use of bisoprolol may reduce AV conduction and myocardial contractility.

CCB 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 in / to the introduction of verapamil in patients receiving beta-blockers may cause severe hypotension and AV blockade.

Antihypertensive drugs central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to decompensated heart failure due to deceleration heart rate and reducing cardiac output, as well as to the appearance of symptoms of vasodilation due to the reduction of the central sympathetic tone.

Combinations requiring special care

BPC, dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine), while the use of bisoprolol may increase the risk of hypotension. In patients with heart failure can not eliminate the risk of further deterioration of the contractile function of the heart.

Class III antiarrhythmics (eg amiodarone) may increase the violation of AV conduction.

The action of beta-blockers for topical application (eg eye drops for glaucoma treatment) may enhance the systemic effects of bisoprolol - marked reduction of 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.

The simultaneous use of bisoprolol with beta-adrenergic agonists (such as isoprenaline, dobutamine) may reduce the effects of both drugs. Bisoprolol combination with agonists affecting the beta- and alpha-adrenergic receptors (such as norepinephrine, epinephrine), may enhance the effects of vasoconstrictor agents occurring with alpha-adrenergic receptors, resulting in an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.

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

Iodine-containing X-ray diagnostic tools for the on / in increase the risk of anaphylactic reactions.

Phenytoin at / in the introduction, means for inhalation anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive action and the likelihood of blood pressure lowering.

The effectiveness of insulin and hypoglycemic agents for oral administration may change the treatment with bisoprolol (masking the symptoms of developing hypoglycemia - tachycardia, increased blood pressure).

The clearance of lidocaine and xanthine (except theophylline) may be reduced due to the possible increase of their plasma concentrations, especially in patients with initially increased clearance of theophylline under the influence of smoking.

The antihypertensive effect of weakening the NSAID (delay sodium and kidney PG synthesis blockade), corticosteroids, and estrogens (delay of sodium ions).

Cardiac glycosides increase the risk of developing or worsening of bradycardia, AV block, cardiac arrest and heart failure.

Diuretics, clonidine, sympatholytic, hydralazine and other antihypertensive drugs may lead to an excessive reduction in blood pressure.

The action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin during treatment with bisoprolol may lengthen.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in blood plasma.

Combinations to be taken into account

Mefloquine while the use of bisoprolol may increase the risk of bradycardia.

MAO inhibitors (except for MAO-B inhibitors) may enhance the antihypertensive effect. Concomitant use can lead to a hypertensive crisis.

Ergotamine increases the risk of peripheral circulatory disorders.

Rifampicin shortens the T1 / 2 bisoprolol.

Dosage and Administration

Inside, in the morning, on an empty stomach, 1 time a day with a small amount of liquid. Tablets should not be chewed or triturate.

In all cases, the receiving mode and selects the dose the doctor for each patient individually, in particular taking into account the patient's heart rate and condition.

Arterial hypertension and coronary heart disease

When hypertension and coronary heart disease drug use Biol® 5 mg 1 time per day. If necessary to increase the dose of 10 mg 1 time per day.

In the treatment of hypertension and angina pectoris the maximum daily dose is 20 mg 1 time / day.

CHF

Home treatment of CHF requires a mandatory drug Biol® the special titration phase and regular medical supervision.

A prerequisite for treatment with Biol® is stable chronic heart failure without acute symptoms.

CHF Biol® drug treatment is started in accordance with the following titration scheme. This may require individual adaptation, 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.

To ensure proper titration process in the initial stages of treatment is recommended to use the drug in smaller doses.

The recommended starting dose is 1.25 mg (Table 1.4. 5 mg) once a day one. Depending on individual tolerance dose should be gradually increased to 2.5 mg (Table 2.1. Biol® preparation 5 mg), 3.75 mg (Table 3/4. 5 mg), 5 mg (Table 1. Drug Biol® 5 mg or Table 2.1. 10 mg), 7.5 mg (Table 4.3. 10 mg) and 10 mg 1 time per day at intervals of at least 2 weeks.

If an increase in the dose of the drug is poorly tolerated by the patient, the dose may be reduced.

The maximum daily dose for the treatment of chronic heart failure is 10 mg 1 time a day.

During titration we recommend regular monitoring of blood pressure, heart rate and increase the severity of symptoms of CHF. 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 flow of CHF, hypotension or bradycardia. In this case, we recommend first of all pay attention to the selection of a dose of concomitant standard therapy. You may also need a temporary reduction in the dose of 5 mg Biol® or withdrawal of treatment. After stabilization, the patient should undertake a re-titration of the dose or continue the treatment.

Impaired renal or hepatic function

Impaired Hepatic or renal function or mild to moderate degree does not usually require dose adjustment.

When expressed violations kidney (Cl creatinine <20 ml / min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be administered with extreme caution.

Elderly patients

Dose adjustment is not required.

There are currently insufficient data on the use of the drug Biol® 5 mg in patients with chronic heart failure, involving a type 1 diabetes, severe impaired renal function and / or liver disease, restrictive cardiomyopathy, congenital heart defects or hemodynamically caused by heart disease. Also still not sufficient data has been obtained relative to CHF patients with myocardial infarction within the past 3 months.

Overdose

Symptoms: arrhythmia, ventricular premature beats, bradycardia, AV block, marked reduction in blood pressure, congestive heart failure, hypoglycemia, akrotsianoz, shortness of breath, bronchospasm, dizziness, fainting, seizures.

Treatment: in the event of an overdose, it is necessary first of all to stop taking the drug, to gastric lavage, take adsorbing means, spend symptomatic therapy.

In severe bradycardia - in / atropine. If the 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 - in / in a plasma-solutions and vasopressors. When hypoglycemia can be shown in / glucagon or dextrose (glucose). When AV blockade - patients should be under constant supervision and be treated with beta-agonists such as epinephrine. If necessary - setting an artificial pacemaker.

When exacerbation of heart failure - in / in the introduction of diuretics, drugs with positive inotropic effect and vasodilators.

When bronchospasm - appointment of bronchodilators, including beta2-agonists and / or aminophylline.

Special instructions

Do not abruptly discontinue the drug Biol® due to the risk of severe arrhythmias and myocardial infarction. Cancellation of a gradually reducing the dose by 25% every 3-4 days.

Monitoring of patients taking the drug Biol® 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 concentrations in diabetic patients (1 in 4 times -5 months).

In elderly patients it is recommended to monitor renal function (1 every 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 50 bpm. / Min.

In the case of elderly patients increasing bradycardia (heart rate> 50 bpm. / Min), marked reduction of blood pressure (SBP <100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue treatment. Before treatment is recommended to study of respiratory function in patients with a history of bronchopulmonary history.

Patients who use contact lenses, you should consider that in the context of drug treatment may decrease the production of tear fluid.

When using Biol® drug in patients with pheochromocytoma have a risk of paradoxical hypertension (if not previously reached effective blockade of the alpha-adrenergic receptors).

In hyperthyroidism bisoprolol may mask certain clinical signs of hyperthyroidism (eg tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because the symptoms can increase.

In diabetes may mask tachycardia caused by hypoglycemia. In contrast, nonselective beta-blockers, almost no increase insulin-induced hypoglycemia and delay recovery of the concentration of glucose in the blood to normal.

With simultaneous use of clonidine its reception can be terminated only after a few days after discontinuation of the drug Biol®.

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

In the case of the need for a planned surgical treatment drug should be discontinued 48 hours before general anesthesia. If the patient has taken the drug before surgery, he should pick up the drugs for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be removed in / atropine (1-2 mg). Drugs that deplete the depot of catecholamines (including reserpine), may enhance the effect of beta-blockers, therefore patients taking these combinations of drugs should be under constant medical supervision in order to identify pronounced reduction in blood pressure and bradycardia.

Patients with bronhospasticheskimi diseases can be prescribed with care cardioselective beta-blockers in the case of intolerance and / or ineffectiveness of other antihypertensive agents. While taking beta-blockers in patients with concomitant asthma may be exacerbated airway resistance. In excess doses Biol® the drug in such patients, there is a risk of bronchospasm.

In case of patients increasing bradycardia (heart rate <50 bpm. / Min), marked reduction of blood pressure (SBP <100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue treatment.

It is recommended to discontinue therapy with Biol® 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).

It is necessary to cancel prior to the study drug concentration in the blood and urine catecholamines, Normetanephrine, vanillylmandelic acid, antinuclear antibody titers.

Smokers efficacy of beta-blockers lower.

Effects on ability to drive and perform other activities that require concentration and speed of psychomotor reactions. During drug treatment Biol® must be careful when driving and doing other potentially hazardous activities that require high concentration and speed of psychomotor reactions.

Release Form

Film-coated tablets 5, 10 mg. According to Table 10. in blister aluminum / aluminum. 3 bl. in a cardboard bundle.

Manufacturer

Sandoz dd, Verovshkova 57, 1000 Ljubljana, Slovenia

Produced by: Salyutas Pharma GmbH, Germany, Otto-von-Guericke-Allee 1 39179 Barleben, Germany.

Claims directed to the consumers of JSC "Sandoz": 125315, Moscow, Leningrad avenue, 72, corp. 3.

Conditions of supply of pharmacies

On prescription.

Storage conditions of Byol

The temperature is not above 25 ° C.

Keep out of the reach of children.

Shelf life

4 years.

Do not use beyond the expiration date printed on the package.