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

Excipients: cellulose microcrystalline 20.0 mg / 40.0 mg, calcium hydrophosphate 51.8 mg / 103.6 mg, corn starch 5.0 mg / 10.0 mg, croscarmellose sodium 1.7 mg / 3.4 mg, magnesium stearate 0.75 mg / 1.5 mg, silicon dioxide colloidal anhydrous 0.75 / 1.5 mg;

film sheath: lactose monohydrate 1.24 mg / 2.48 mg, hypromellose 0.96 mg / 1.92 mg, titanium dioxide 0.90 mg / 1.80 mg, macrogol-4000 0.34 mg / 0.68 mg, iron dye (III) oxide yellow 0.06 mg / 0.12 mg, iron dye (III) red oxide - / 0,002 mg.

Description:

Tablets, film-coated, 5 mg: light yellow, round, biconvex tablet with a cross-shaped risk on one side and engraved “BIS 5 "on the other, on a broken white color.

Tablets, film-coated, 10 mg: yellow, round, biconvex tablet with a cross-shaped risk on one side and engraved “BIS 10 "on the other, on a broken white color.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Bisoprolol - selective beta₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. As for the other beta_1-adrenoblockers, the mechanism of action for arterial hypertension is unclear. At the same time, it is known that bisoprolol reduces the activity of renin in the blood plasma, reduces the need for myocardium in oxygen, reduces the heart rate (Heart rate). Provides antihypertensive, antiarrhythmic and antianginal action.

Blocking in low doses of beta₁-adrenoceptors of the heart, reduces catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces the intracellular current of calcium ions, inhibits all cardiac functions, reduces atrioventricular (AV) conductivity and excitability. If the therapeutic dose is exceeded, beta₂-adrenoblocking action. The total peripheral vascular resistance at the beginning of the drug application, in the first 24 hours, increases (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), returns to the initial value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is associated with a decrease in the minute volume of blood,sympathetic stimulation of peripheral vessels, decreased activity of the sympathoadrenal system (CAS) (is of great importance for patients with initial hypersecretion of renin), restoration sensitivity in response to lowering blood pressure (BP) and affecting the central nervous system (CNS). With arterial hypertension, the effect develops in 2-5 days, a stable effect is observed after 1-2 months.

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of decreased contractility and other myocardial functions, diastole lengthening, and improved myocardial perfusion. By increasing the final diastolic pressure in the left ventricle and increasing the stretching of the ventricular muscle fibers, the need for oxygen may increase, especially in patients with chronic heart failure (CHF).

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it exerts a less pronounced effect on organs containing beta₂-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries,bronchus and uterus) and carbohydrate metabolism; does not cause retention of sodium ions in the body; the severity of atherogenic action does not differ from that of propranolol.

Pharmacokinetics:

Bisoprolol is almost completely absorbed from the gastrointestinal tract, eating does not affect absorption. Bioavailability is about 90%.

Time to reach the maximum concentration in the blood plasma (TC_m_Oh) 2-4 hours after ingestion. Connection with blood plasma proteins - 26-33%. Metabolized in the liver, metabolites of bisoprolol do not have pharmacological activity. The half-life (T_1/2) is 9-12 hours, which makes it possible to use the drug once a day.

It is excreted by the kidneys - 50% unchanged, less than 2% through the intestine.

Permeability through the blood-brain and placental barrier is low, in small amounts is excreted in breast milk.

Indications:

- Arterial hypertension;

- ischemic heart disease (IHD): prevention of attacks of stable angina pectoris;

- chronic heart failure (as part of combination therapy).

Contraindications:

- Hypersensitivity to bisoprolol or to any of the components of the drug and other beta-blockers;

- acute heart failure and chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- collapse;

- atrioventricular (AV) blockade II-III degree, without a pacemaker;

- sinoatrial blockade;

- syndrome of weakness of the sinus node;

- bradycardia (heart rate before treatment less than 50 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

- cardiomegaly (no signs of heart failure);

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

- severe peripheral circulatory disturbances;

- Raynaud's syndrome;

- metabolic acidosis;

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

- concomitant use of floktaphenin and sultopride;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- age to 18 years (efficacy and safety not established).

Carefully:

- Bronchospasm (bronchial asthma, obstructive airway disease);

- conducting desensitizing therapy;

- hyperthyroidism;

- Type 1 diabetes mellitus and diabetes mellitus with significant fluctuations the concentration of glucose in the blood;

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

- severe violations of liver function;

- psoriasis;

- violations of peripheral circulation (at the beginning of therapy, there may be an increase in symptoms);

- general anesthesia;

- myasthenia gravis;

- AV blockade of the 1st degree;

- angina of Prinzmetal;

- restrictive cardiomyopathy;

- congenital heart disease or heart valve disease with severe hemodynamic violations;

- chronic heart failure with myocardial infarction during the last 3 months;

- depression (including in the anamnesis);

- pheochromocytoma (necessarily simultaneous use of alpha-blockers);

- strict diet;

- allergic reactions in the anamnesis.

Pregnancy and lactation:

Bisoprolol does not have direct cytotoxic, mutagenic and teratogenic effects, but it has pharmacological effects that can have harmful effects on the course of pregnancy and / or on the fetus or newborn.

Usually beta-adrenoblockers reduce placental perfusion, which leads to a slowing of fetal growth, fetal death, miscarriage or premature birth.The fetus and the newborn child may experience pathological reactions, such as intrauterine growth retardation, hypoglycemia, bradycardia.

Biol® should not be used during pregnancy, it can be used if the benefit to the mother exceeds the risk of side effects in the fetus and / or the child. When treatment with Biol® is considered necessary, blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child monitored, and in the event of undesirable pregnancy and / or fetal events, alternative therapies . You should carefully examine the newborn after delivery. Symptoms of hypoglycemia and bradycardia usually arise during the first 3 days of life.

Breastfeeding period

There is no data on the penetration of bisoprolol into breast milk. Therefore, the use of Biol® is not recommended for women during lactation.

If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The preparation Biol ® is taken orally, in the morning on an empty stomach, once a day 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.

In all cases, the regimen and dosage are selected by the doctor for each patient individually, in particular, taking into account the heart rate and the patient's condition.

Hypertension and coronary artery disease

With arterial hypertension and ischemic heart disease, Biol® is used 5 mg once a day. If necessary, increase the dose to 10 mg once a day.

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

Chronic heart failure

The initiation of treatment with CHF with Biol® requires a special phase of titration and regular medical supervision.

A precondition for treatment with Biol® is stable chronic heart failure without signs of exacerbation.

Treatment of CHF with Biol® 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 the drug in smaller doses.

The recommended initial dose is 1.25 mg (1/4 tablets of 5 mg) once a day. Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg (1/2 Biol® 5 mg tablet), 3.75 mg (3/4 5 mg tablets), 5 mg (1 tablet of Biol® on 5 mg or 1/2 tablet of 10 mg each), 7.5 mg (3/4 tablet of 10 mg) and 10 mg once a day at intervals of not less than 2 or more weeks. If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible.

The maximum daily dose for the treatment of CHF is 10 mg 1 time per day.

During the titration, regular monitoring of blood pressure is recommended. Heart rate and symptoms of increased severity of CHF Exacerbation of symptoms of CHF is possible for the first day of the drug.

During the titration phase or after it, temporary deterioration of 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 Biol® 5 mg or to cancel treatment.

After stabilization of the patient's condition, a repeated titration dose, or continue treatment.

Impaired renal or hepatic function

A mild or moderate degree of liver or kidney disorder usually does not require a dose adjustment.

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 carried out with extreme caution.

Elderly patients

Correction of the dose is not required.

To date, there is insufficient data on the use of 5 mg Biol® in patients with CHF associated with type 1 diabetes mellitus, severe renal and / or hepatic impairment, restrictive cardiomyopathy, congenital heart disease, or hemodynamically caused heart failure. Also, sufficient data have not yet been obtained regarding patients with CHF with myocardial infarction during the last 3 months.

Side effects:

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0,01%,but less than 0.1%; very rarely - less than 0.01%, including individual reports.

From the cardiovascular system: Often - Decrease in heart rate (bradycardia, especially in patients with CHF), palpitation; often - marked decrease in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disorders, sensation of coldness in the extremities (paresthesia); infrequently violation AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, worsening of CHF flow with development of peripheral edema (swelling of the ankles, feet, dyspnea), chest pain.

From the nervous system: often - dizziness headache, fatigue, fatigue, sleep disorders, depression, anxiety; rarely - confusion or short-term memory loss, "nightmarish" dreams, hallucinations, myasthenia gravis, tremor, muscle cramps.

Usually, these phenomena are of an easy nature and usually take place within 1-2 weeks after the start of treatment.

From the sense organs: rarely - impaired vision, reduced tearing (should be taken into account when wearing contact lenses), tinnitus, hearing loss, ear pain; very rarely - dryness and soreness of the eyes, conjunctivitis, taste disorders.

From the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or obstructive airway disease; rarely - Allergic rhinitis; nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, abdominal pain; rarely - Hepatitis, increased activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase), increased bilirubin concentration, change in taste.

From the musculoskeletal system: infrequently - Arthralgia, pain in the back.

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

Laboratory indicators: rarely - increase in concentration triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, and leukopenia.

Allergic reactions: rarely - skin itching, rash, hives.

From the skin: rarely - increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions; rarely - alopecia, beta-adrenoblockers can aggravate the course of psoriasis.

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

Overdose:

Symptoms: arrhythmia, ventricular extrasystole, pronounced bradycardia, AV blockade, marked decrease in blood pressure, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: when an overdose occurs, first of all, stop taking the drug, rinsing the stomach, taking adsorbents, and taking symptomatic therapy.

With severe bradycardia - intravenous atropine. If the effect is insufficient, with caution, you can enter 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, intravenous injection of plasma-substituting solutions and vasopressors.

In hypoglycemia, intravenous administration of glucagon or intravenous dextrose (glucose) may be indicated.

When AV blockade: patients should be under constant supervision,and receive treatment with beta-adrenomimetics, such as epinephrine. If necessary - staging an artificial pacemaker.

During exacerbation flow CHF intravenous diuretics, drugs with a positive inotropic effects and vasodilators.

When bronhospazme - the appointment of bronchodilators, including beta₂- adrenomimetics and / or aminophylline.

Interaction:

The effectiveness and tolerability of bisoprolol may be influenced by simultaneous intake of other drugs. This interaction can also occur when two drugs are taken in a short time. The doctor should be informed about the acceptance of other drugs, even if they are received without a doctor's prescription (ie, non-prescription drugs).

Unrecommended combinations

Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

Blocks of "slow" calcium channels

(BCC) such as verapamil and to a lesser extent diltiazem when used with bisoprolol may lead to a decrease in contractile the ability of the myocardium and the violation of AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Hypotensive drugs central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to decompensation of CHF due to a decrease in heart rate and a reduction in cardiac output, as well as to the appearance of symptoms of vasodilation due to a decrease in the central sympathetic tone.

Combinations requiring special care

BCCC derivatives of dihydropyridine (eg, nifedipine, felodipine, amlodipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension. In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out.

Antiarrhythmic drugs of III class (eg, amiodarone) can increase the violation AV conductivity.

Act beta-blockers for topical application (for example, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol: a marked decrease in blood pressure, a decrease in heart rate.

Parasympathetichasicki at concomitant use with bisoprolol may exacerbate AV conduct and increase the risk of development bradycardia.

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 alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using nonselective beta-blockers.

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 radiopaque diagnostic tools for intravenous administration increase the risk of developing anaphylactic reactions.

Phenytoin with intravenous administration, means for inhalation anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of reducing blood pressure.

Efficiency insulin and hypoglycemic agents for oral administration can change in the treatment of bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

Clearance lidocaine and xanthines (except theophylline) may decrease due to a possible increase in their concentration in the blood plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Antihypertensive effect weaken nonsteroidal anti-inflammatory drugs (delay of sodium ions and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion delay).

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

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensives may lead to an excessive decrease in blood pressure.

The action of nondepolarizing muscle relaxants and anticoagulant effect coumarins during the treatment with bisoprolol may be prolonged.

Tricyclic and tetracyclic antidepressants, antipsychotics (antipsychotics), ethaneol, saddleamocular and hypnotics increase the inhibition of the central nervous system.

Unhydrated alkaloids ergot increase the risk of peripheral circulatory disorders.

Sulfasalazine enhances concentration of bisoprolol in blood plasma.

Combinations, which should be taken into account

Meflokhin with simultaneous use with bisoprolol may increase the risk of developing bradycardia.

Inhibitors of monoamine oxidase (MAO) (with the exception of MAO inhibitors type B) can enhance the antihypertensive effect. Simultaneous application can lead to the development of hypertensive crisis.

Ergotamine increases the risk of peripheral circulatory disorders.

Rifampicin shortens the half-life of bisoprolol.

Special instructions:

Do not abruptly discontinue treatment with Biol® because of the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose by 25% every 3-4 days

Monitoring the condition of patients taking Biol ® should include a measurement of heart rate and blood pressure (at the beginning of treatment - every day, then every 3 to 4 months), ECG, blood glucose in patients with diabetes mellitus (1 time in 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 heart rate less than 50 beats per minute.

If elderly patients develop an increasing bradycardia (heart rate less than 50 beats per minute), a marked decrease in blood pressure (systolic blood pressure less than 100 mm Hg), an atrioventricular block, it is necessary to reduce the dose or stop treatment. Before the start of treatment, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis.

Patients who use contact lenses should take into account that against the background of drug treatment, a decrease in the production of tear fluid is possible.

When using Biol ® in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless an effective blockade of alpha-adrenergic receptors has been previously achieved).

With hyperthyroidism bisoprolol canmask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated, as it can strengthen symptoms.

In diabetes mellitus can mask tachycardia caused by hypoglycemia. In contrast to non-selective beta-blockers, it does not substantially increase insulin-induced hypoglycemia and does not delay the restoration of glucose concentration in the blood to a normal value.

With the simultaneous use of clonidine, its administration may be discontinued only a few days after the withdrawal of Biol®.

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.

If it is necessary to conduct routine surgical treatment, the drug should be discontinued 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.

Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Medicines that deplete the catecholamine depot (incl. reserpine), can enhance the action of beta-blockers, so patients who take such combinations of drugs should be under constant medical supervision to detect a marked decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases can be cautiously prescribed cardioselective beta-blockers in the case of intolerance and / or ineffectiveness of other antihypertensive agents. Against the background of taking beta-blockers in patients with concomitant bronchial asthma, airway resistance can increase. When the dose of Biol® is exceeded in such patients, there is a danger of developing bronchospasm.

If patients develop an increasing bradycardia (heart rate less than 50 beats per minute), a marked decrease in blood pressure (systolic blood pressure is less than 100 mm Hg) AV blockade, it is necessary to reduce the dose or stop treatment.

It is recommended to stop therapy with Biol ® in 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).

It is necessary to cancel the drug before testing the concentration in the blood and urine catecholamines, normetanephrine, vanillylmandelic acid, titers of antinuclear antibodies.

In smokers, the effectiveness of beta-blockers is lower.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment with Biol®, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 5 mg and 10 mg.

Packaging:

Primary packaging: 10 tablets in a blister of aluminum / aluminum.

Secondary packaging: for 3, 5 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-001734/09

Date of registration:10.03.2009 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp12.02.2017

Illustrated instructions

Instructions

Biol® (Byol®)