Biol, pills 5mg, 30pcs

Composition

1 film-coated tablet contains:

Active ingredient:

bisoprolol hemifumarate 5 mg.

Auxiliary substances:

microcrystalline cellulose,

calcium hydrophosphate,

corn starch,

croscarmellose sodium,

magnesium stearate,

colloidal anhydrous silicon dioxide.

Composition of the film shell:

lactose monohydrate, hypromellose, titanium dioxide, macrogol-4000, iron (III) oxide yellow dye.

Pharmacological action

Selective beta-1-adrenoblocker without its own sympathomimetic activity. It does not have a membrane-stabilizing effect. Reduces the activity of blood plasma renin, reduces the need for myocardial oxygen, reduces the heart rate at rest and during exercise.

It has antihypertensive, antiarrhythmic and antianginal effects. Blocking the beta-1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cAMP from ATP, reduces the intracellular flow of calcium ions, and has a negative chrono -, dromo -, batmo-and inotropic effect. Inhibits conduction and excitability, slows down AV conduction. The total peripheral vascular resistance increases in the first 24 hours of the drug use (as a result of a reciprocal increase in the activity of α-adrenergic receptors and elimination of β2-adrenergic receptor stimulation), which returns to the initial value after 1-3 days, and decreases with prolonged use.

The antihypertensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (it is more important for patients with initial hypersecretion of renin), restoration of sensitivity of the aortic arch baroreceptors (there is no increase in their activity in response to a decrease in blood pressure and influence on the central nervous system). With arterial hypertension, the effect occurs in 2-5 days, a stable hypotensive effect in 1-2 months.

The antianginal effect is due to a decrease in the myocardial oxygen demand as a result of a decrease in heart rate and contractility, an elongation of the diastole, and an improvement in myocardial perfusion. By increasing the final diastolic pressure in the left ventricle and increasing the stretching of the muscle fibers of the ventricles, it can increase the need for oxygen, especially in patients with chronic heart failure.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors ( tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers, and a slowdown in AV conduction (mainly in the antegrade and, to a lesser extent, in the retrograde directions through the AV node) and along additional pathways.

 When used in medium therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on the organs containing beta-2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism. It does not cause retention of sodium ions in the body. When the dose is increased above the therapeutic dose, it has a beta-2-adrenoblocking effect.

Pharmacokinetics

Absorption

Bisoprolol is almost completely absorbed from the gastrointestinal tract, food intake does not affect absorption. Bioavailability is about 90%. T max in blood plasma is 2-4 hours after oral use.

Distribution and metabolism

Binding to plasma proteins is 26-33%. Metabolized in the liver, bisoprolol metabolites do not have pharmacological activity. Permeability through the blood-brain barrier and placental barrier is low, and small amounts are excreted in breast milk.

Elimination

of T 1/2 is 9-12 hours, which makes it possible to use the drug 1 time/day. It is excreted by the kidneys (50% unchanged), less than 2% – through the intestines.

Indications

• Arterial hypertension.
• IHD (prevention of angina attacks).

Use during pregnancy and lactation

The use of Biol during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

The drug is excreted in breast milk, so when taking the drug during lactation, you should stop breastfeeding.

Contraindications

• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg, especially in myocardial infarction).
• Acute heart failure, chronic heart failure in the stage of decompensation.
• Cardiogenic shock; collapse, pulmonary edema.
• AV blockage of II and III degrees (without pacemaker installation).
• Sinoatrial blockade.
• Sinus node weakness syndrome.
• Severe sinus bradycardia ( heart rate less than 50 beats / min).
• Severe stages of peripheral circulatory disorders, Raynaud’s disease.
• Concomitant use of MAO inhibitors (with the exception of MAO type B).
• Metabolic acidosis.
• Severe forms of bronchial asthma and chronic obstructive pulmonary disease (in the anamnesis).
• Age up to 18 years (efficacy and safety have not been established).
• Hypersensitivity to bisoprolol and other components of the drug and to other beta-blockers.

With caution:

• Severe liver failure.
• Severe renal failure.
• Thyrotoxicosis.
• Psoriasis.
• Myasthenia
• gravis is a grade I AV block.
• Prinzmetal angina pectoris.
• Depression (including a history of depression).
• Pheochromocytoma (simultaneous use of alpha-blockers is mandatory).
• Diabetes mellitus.
• General anesthesia/surgery.
• Severe allergic reactions (in the anamnesis).

Side effects

The frequency of adverse reactions listed below was determined according to the following (WHO classification): very common (≥ 10%); common (≥1%, but

From the cardiovascular system: very often-a decrease in heart rate (bradycardia, especially in patients with CHF), palpitation sensation; often – a pronounced decrease in blood pressure (especially in patients with CHF), angiospasm (increased peripheral circulatory disorders, a feeling of cold in the extremities (paresthesia); infrequently – violation of AV conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, worsening of the course CHF with the development of peripheral edema (swelling of the ankles, feet, shortness of breath), chest pain.

From the nervous system: often – dizziness, headache, asthenia, increased fatigue, sleep disorders, depression, anxiety; rarely-confusion or short-term memory loss, nightmares, hallucinations, myasthenia gravis, tremor, muscle cramps. Usually, these phenomena are mild and usually disappear within 1-2 weeks after the start of treatment.

From the sensory organs: rarely-visual impairment, reduced tear production (should be taken into account when wearing contact lenses), tinnitus, hearing loss, ear pain; very rarely – dry and painful eyes, conjunctivitis, taste disorders.

From the respiratory system: infrequently-bronchospasm in patients with bronchial asthma or obstructive airway diseases; 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 (ALT, AST), increased bilirubin concentration, taste changes.

Musculoskeletal disorders: infrequently-arthralgia, back pain.

From the genitourinary system: very rarely – violation of potency, weakening of libido.

From the laboratory parameters: rarely-an increase in the concentration of triglycerides in the blood; in some cases – thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rarely-skin pruritus, rash, urticaria.

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

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

Interaction

Class I antiarrhythmic agents (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility.

Class III antiarrhythmic agents (such as amiodarone) may increase the violation of AV conduction.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

Parasympathomimetics, when used concomitantly with bisoprolol, may increase the violation of AV conduction and increase the risk of bradycardia.

Concomitant use of Biol® with beta-adrenomimetics (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics that affect beta-and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) may increase 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 to occur with non-selective beta-blockers.

Mefloquine, when co-administered with bisoprolol, may increase the risk of developing bradycardia.

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 agents for intravenous use increase the risk of anaphylactic reactions.

Phenytoin with intravenous use, agents for inhalation anesthesia (hydrocarbon derivatives) increase the severity of cardiodepressive effects and the likelihood of lowering blood pressure.

The effectiveness of insulin and hypoglycemic agents for oral use may change during treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

Clearance of lidocaine and xanthines (other than theophylline) may decrease due to a possible increase in their plasma concentrations, especially in patients with an initially increased clearance of theophylline under the influence of smoking.

The antihypertensive effect is weakened by NSAIDs (sodium ion retention and blockade of prostaglandin synthesis by the kidneys), corticosteroids and estrogens (sodium ion retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic agents increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure.

Nifedipine can lead to a significant decrease in blood pressure.

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

The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins may be prolonged during treatment with bisoprolol.

Tricyclic and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and sleeping pills increase CNS depression.

Concomitant use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

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

Ergotamine increases the risk of developing peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens T1 / 2 of bisoprolol.

How to take, course of use and dosage

Biol® is taken orally, in the morning on an empty stomach,1 time/day 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 mode of use and dose is selected by the doctor for each patient individually, in particular, taking into account the patient’s heart rate and condition.

Arterial hypertension and CHD

In patients with arterial hypertension and CHD, Biol® is used 5 mg 1 time / day. If necessary, the dose is increased to 10 mg 1 time/day.

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

Chronic heart failure (CHF)

Starting treatment for CHF with Biol® requires a special titration phase and regular medical monitoring.

A prerequisite for treatment with Biol® is stable CHF without signs of exacerbation. Treatment of CHF with Biol ® begins according to the following titration schedule. However, individual adjustment may be required depending on how well the patient tolerates the prescribed dose, i. e. the dose can only be increased if the previous dose was well tolerated.

To ensure an appropriate titration process at the initial stages of treatment, it is recommended to use the drug in smaller doses.

The recommended starting dose is 1.25 mg (1/4 tablet of 5 mg) 1 time/day. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg (1/2 tab. 5 mg),3.75 mg (3/4 tab. 5 mg),5 mg (1 tab. 5 mg or 1/2 tab. 10 mg),7.5 mg (3/4 tab. 10 mg) and 10 mg 1 time/day with an interval of at least 2 or more weeks. If an increase in the dose of the drug is poorly tolerated by the patient, it is possible to reduce the dose.

The maximum daily dose in the treatment of CHF is 10 mg 1 time/day.

During titration, regular monitoring of blood pressure, heart rate, and symptoms of increasing CHF severity is recommended. Worsening of the symptoms of CHF is possible from the first day of use of the drug.

During or after the titration phase, there may be a temporary deterioration in the course of CHF, hypotension, or bradycardia. In this case, it is recommended, first of all, to pay attention to the selection of the dose of concomitant standard therapy. It may also be necessary to temporarily reduce the dose of Biol® 5 mg or discontinue treatment.

After the patient’s condition stabilizes, the dose should be re-titrated or the treatment should be continued.

Impaired kidney or liver function

Mild or moderate hepatic or renal impairment usually does not require dose adjustment. In patients with severe renal impairment (creatinine clearance less than 20 ml / min) and in patients with severe liver diseases, the maximum daily dose is 10 mg. Increasing the dose in such patients should be carried out with extreme caution.

Elderly patients do not need to adjust the dose.

To date, there are insufficient data on the use of Biol® 5 mg in patients with CHF associated with type 1 diabetes mellitus, severe renal and/or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or hemodynamically caused heart disease. Also, until now, insufficient data have been obtained on patients with CHF with myocardial infarction in the last 3 months.

Overdose

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

Treatment: first of all, you should stop taking the drug, perform gastric lavage, take adsorbents, and conduct symptomatic therapy. With severe bradycardia-IV use of atropine. If the effect is insufficient, you can use caution to introduce a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily install an artificial pacemaker. With a pronounced decrease in blood pressure, intravenous use of plasma – substituting solutions and vasopressors is recommended. In hypoglycemia, intravenous use of glucagon or intravenous use of dextrose (glucose) may be indicated. With AV block: patients should be constantly monitored and treated with beta-adrenomimetics, such as epinephrine.

If necessary, an artificial pacemaker can be installed. If the course of CHF worsens, intravenous diuretics, drugs with a positive inotropic effect, as well as vasodilators are administered. With bronchospasm-the appointment of bronchodilators, including beta-2-adrenomimetics and / or aminophylline.

Special instructions

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

Monitoring of the condition of patients taking Biol® should include measuring heart rate and blood pressure (at the beginning of treatment – daily, then – once every 3-4 months), performing an ECG, determining the concentration of blood glucose in patients with diabetes mellitus (once every 4-5 months).

In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months).

The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

In case of increasing bradycardia (heart rate less than 50 beats/min), a marked decrease in blood pressure (systolic blood pressure less than 100 mm Hg), AV-blockade in elderly patients, it is necessary to reduce the dose or discontinue treatment.

Before starting treatment, it is recommended to conduct a study of the function of external respiration in patients with a burdened bronchopulmonary history.

Patients who use contact lenses should take into account that during treatment with the drug, it is possible to reduce the production of tear fluid.

When using Biol® in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if effective alpha-adrenergic blockade is not achieved beforehand).

In hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated, since it can increase symptoms.

In diabetes mellitus, bisoprolol can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal levels.

When taking clonidine at the same time, its use can be stopped only a few days after the withdrawal of Biol®.

It is possible to increase the severity of the hypersensitivity reaction and the lack of effect from conventional doses of epinephrine against the background of a burdened allergic history.

If surgical intervention is necessary, the drug is withdrawn 48 hours before the start of general anesthesia. If the patient took the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effect.

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

Medicines that reduce catecholamine stores (including:reserpine), can increase the effect of beta-blockers, so patients taking such drug combinations should be constantly monitored by a doctor for a pronounced decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases may be cautiously prescribed cardioselective beta-blockers in case of intolerance and/or ineffectiveness of other antihypertensive agents. When taking beta-blockers, patients with concomitant bronchial asthma may experience increased airway resistance. If the dose of Biol® is exceeded, such patients are at risk of developing bronchospasm.

If patients show increasing bradycardia (heart rate less than 50 beats / min), a marked decrease in blood pressure (systolic blood pressure less than 100 mm Hg), AV blockade, it is necessary to reduce the dose or discontinue treatment.

It is recommended to discontinue therapy with Biol® if depression develops.

Do not abruptly interrupt treatment due to the risk of developing severe arrhythmias and myocardial infarction. Discontinuation of the drug is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days).

The drug should be discontinued before testing the concentration of catecholamines, normetanephrine, vanillinmindalic acid, and anti-nuclear antibody titers in the blood and urine.

In smoking patients, the effectiveness of beta-blockers is lower.

Influence on the ability to drive motor vehicles and manage mechanisms

During treatment with Biol®, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Biol tablets.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Shelf

life is 4 years.

Active ingredient

Bisoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Arrhythmia, Hypertension