Biol tablets: instructions for use, special instructions, price, reviews, analogues

Compound

One tablet may contain 2.5 mg, 5 mg or 10 mg of bisoprolol hemifumarate .
The excipients are: microcrystalline cellulose, calcium hydrogen phosphate, corn starch, croscarmellose sodium, magnesium stearate and colloidal anhydrous silica.

The film shell of the tablets is made of lactose monohydrate, hypromellose, titanium dioxide, macrogol 4000.

The dyes used were: yellow and red iron (III) oxide (for a dosage of 10 mg).

Pharmacodynamics and pharmacokinetics

Bisoprolol is a selective β1-blocker that does not have sympathomimetic activity or membrane-stabilizing effect. The mechanism of action of the active compound in the treatment of arterial hypertension is still unclear. However, bisoprolol in the bloodstream reduces the activity of the proteolytic enzyme - renin , reduces the need of the heart muscle for oxygen and heart rate, and has a hypotensive, antiarrhythmic and antianginal effect.

Low doses of the drug lead to blocking of β1-adrenergic receptors of the heart, which inhibits the conversion of cyclic AMP from ATP , stimulated by catecholamines , which reduces the rate of intracellular flow of calcium ions, inhibits heart function, reducing its excitability and atrioventricular conduction. Taking a larger therapeutic dose of the drug causes a β2-adrenergic blocking effect. Due to the reciprocal increase in the activity of α-adrenergic receptors and the elimination of stimulation of β2-adrenergic receptors, the level of total peripheral vascular resistance increases on the first day of therapy, and then after 2-3 days it returns to the original level, and with prolonged use it decreases.

The antihypertensive effect of Bisoprolol is associated with a decrease in such indicators as minute blood , as well as with sympathetic stimulation of vessels in the periphery, with a decrease in the activity of the sympathetic-adrenal system and restoration of the ability to respond to a decrease in blood pressure . In patients with arterial hypertension, the effect develops on days 2-5 of therapy; 1-2 months are needed to achieve a stable effect.

The antianginal effect of the drug is ensured by a decrease in the oxygen demand of the heart muscle: not only contractility, but also other myocardial functions are reduced, diastole is prolonged and myocardial perfusion is improved. An increase in the final diastolic pressure in the left ventricular chamber and an increase in stretch can increase the need for muscle fibers for oxygen, especially in chronic heart failure (CHF) .

Biol in average therapeutic doses has a less pronounced effect on organs with β2-adrenergic receptors and carbohydrate metabolism, in contrast to non-selective β-blockers .

Pharmacokinetics of Bisoprolol

After oral administration, absorption from the gastrointestinal tract occurs almost completely - approximately 90%, regardless of nutrition. It takes 2 to 4 hours to reach maximum concentration in the bloodstream. The active compound binds to plasma proteins in the blood by 26-33%. After conversion in the liver, metabolites that do not have pharmacological activity. The half-life is 9-12 hours, so Biol can be taken once a day.

Excretion is primarily by the kidneys - up to 50% of unchanged substance, 2% is eliminated through the intestines.

Bisoprolol has low permeability through the blood-brain and placental barriers and is excreted in small quantities in milk.

Biol, 50 pcs., 10 mg, film-coated tablets

The effectiveness and tolerability of bisoprolol may be affected by the simultaneous use of other drugs. Such interaction can also occur in cases where two drugs are taken after a short period of time. The doctor must be informed about taking other drugs, even if they are taken without a doctor’s prescription (i.e., over-the-counter drugs).

Combinations not recommended

Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and myocardial contractility.

CCBs such as verapamil, and to a lesser extent diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block.

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

Combinations requiring special caution

CCBs, dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine), when used simultaneously with bisoprolol, may increase the risk of developing arterial hypotension. In patients with CHF, the risk of subsequent deterioration in cardiac contractility cannot be excluded.

Class III antiarrhythmic drugs (eg amiodarone) may worsen AV conduction disturbances.

The effect of beta-blockers for local use (for example, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol - a pronounced decrease in blood pressure, a decrease in heart rate.

Parasympathomimetics, when used simultaneously with bisoprolol, may enhance AV conduction disturbances and increase the risk of developing bradycardia.

The simultaneous use of bisoprolol with beta-agonists (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenergic agonists that affect beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.

Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol.

Iodine-containing radiopaque diagnostic agents for intravenous administration increase the risk of developing anaphylactic reactions.

Phenytoin, when administered intravenously, and agents for inhalation anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of lowering blood pressure.

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

The clearance of lidocaine and xanthines (except theophylline) may be reduced due to a possible increase in their concentration in the blood plasma, 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 PG synthesis by the kidneys), corticosteroids and estrogens (sodium ion retention).

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

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can 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, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression.

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

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Combinations to Consider

Mefloquine, when used simultaneously with bisoprolol, may increase the risk of bradycardia.

MAO inhibitors (except MAO type B inhibitors) may enhance the antihypertensive effect. Simultaneous use may lead to the development of a hypertensive crisis.

Ergotamine increases the risk of developing peripheral circulatory disorders.

Rifampin shortens T1/2 of bisoprolol.

Contraindications

hypersensitivity to the constituent components or other β-blockers ;
acute or chronic failure of cardiac function, incl. at the stage of decompensation, which requires inotropic support;
metabolic acidosis;
collapse;
therapy with MAO inhibitors and 14 days after discontinuation (risk of a significant increase in the hypotensive effect);
cardiomegaly;
cardiogenic shock;
Raynaud's syndrome;
sinoatrial, AV blockade, partial (II degree) or complete, without the use of a pacemaker ;
sinus node dysfunction;
bradycardia (with heart rate up to 50 beats per minute);
arterial hypotension with systemic blood pressure up to 90 mm Hg. Art.;
severe form of bronchial asthma or chronic obstructive pulmonary disease , as well as a history;
peripheral circulatory disorders;
pheochromocytoma;
taking Floctafenine or Sultopride ;
age category: persons under 18 years of age;
breastfeeding or pregnant women.

Can be used with caution:

combination with desensitizing therapy ;
hyperthyroidism;
psoriasis;
type 1 diabetes mellitus glucose ;
renal failure with creatinine less than 20 ml per 1 min;
severe liver dysfunction;
partial AV block of the 1st degree;
restrictive cardiomyopathy;
angina ;
congenital heart disease or heart valve , accompanied by hemodynamic disturbances;
chronic failure of cardiac function, recent myocardial infarction (up to 3 months);
depression or a history of depression;
for pheochromocytoma and complex treatment with α-blockers ;
strict diet .

Biol, 30 pcs., 2.5 mg, film-coated tablets

Treatment with Biol® should not be abruptly interrupted due to 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 the drug Biol® should include measuring heart rate and blood pressure (at the beginning of treatment - daily, then - once every 3-4 months), conducting an ECG, determining the concentration of blood glucose in patients with diabetes mellitus (once every 4 months). -5 months).

In elderly patients, it is recommended to monitor renal function (once every 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.

If increasing bradycardia (heart rate less than 50 beats/min), a pronounced decrease in blood pressure (sBP less than 100 mmHg), or AV blockade is detected in elderly patients, it is necessary to reduce the dose or stop treatment. Before starting treatment, it is recommended to conduct a study of external respiratory function in patients with a burdened bronchopulmonary history.

Patients who use contact lenses should take into account that during treatment with the drug, the production of tear fluid may decrease.

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

In hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (for example, tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated as it can increase symptoms. In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal values. When using clonidine simultaneously, its use can be discontinued only a few days after discontinuation of the Biol® drug.

It is possible that the severity of the hypersensitivity reaction may increase and there will be no effect from usual doses of epinephrine against the background of a burdened allergic history.

If planned surgical treatment is necessary, the drug should be discontinued 48 hours before general anesthesia. If the patient took the drug before surgery, he should select a drug for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous atropine (1–2 mg). Drugs that deplete the catecholamine depot (including reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect a pronounced decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases may be prescribed cardioselective beta-blockers with caution in case of intolerance and/or ineffectiveness of other antihypertensive drugs. While taking beta-blockers in patients with concomitant bronchial asthma, airway resistance may increase. If the dose of Biol® is exceeded in such patients, there is a risk of developing bronchospasm.

If increasing bradycardia (heart rate less than 50 beats/min), a pronounced decrease in blood pressure (sBP less than 100 mm Hg), or AV block is detected in patients, it is necessary to reduce the dose or stop treatment.

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

Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmias and myocardial infarction. The drug is discontinued gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 3-4 days).

The drug should be discontinued before testing the concentrations of catecholamines, normetanephrine, vanillinmandelic acid, and antinuclear antibody titers in the blood and urine. Beta blockers are less effective in smokers.

Impact on the ability to drive vehicles and perform other activities that require concentration and speed of psychomotor reactions.

During treatment with Biol®, care must be taken when driving vehicles and performing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Side effects

Biol tablets can cause unwanted reactions, the frequency of occurrence and manifestations of which differ:

From the side of the cardiovascular system, very often (in ≤10% of patients) there is a decrease in heart rate and the development of bradycardia , a feeling of palpitations ; less than 1% of patients “often” experienced a decrease in blood pressure, vasospasm , paresthesia , infrequently (≤0.1%) - AV conduction disturbances, block and cardiac arrest arrhythmia , orthostatic hypotension , worsening CHF , peripheral edema and chest pain occurred .
“Frequent” adverse reactions of the nervous system and sensory organs: dizziness , headaches , asthenia , fatigue, anxiety, sleep disturbances, depression , rare cases (≤0.01%) of confusion, short-term memory loss, nightmares, hallucinations , myasthenia , tremor , convulsions , visual disturbances, decreased lacrimation and dryness (important to consider when using lenses), possible noise, ear pain and hearing loss, conjunctivitis .
bronchospasm develops against the background of bronchial asthma or COPD ; Allergic rhinitis rarely occurs .
Nausea, vomiting, constipation or diarrhea , dry mouth, hepatitis , increased ALT and AST bilirubin concentrations , and rarely triglycerides .
Cases of arthralgia and back pain are uncommon.
Very rarely, patients complain of impaired potency and weakened libido.
There have been isolated reports of thrombocytopenia , agranulocytosis , and leukopenia .
Rare allergic reactions have manifested themselves in the form of skin itching , rash and urticaria .
On the part of the epidermis , sweating rarely increased, hyperemia , exanthema , and psoriasis-like reactions occurred; even more rarely - alopecia, exacerbation of psoriasis .
After stopping taking Biol tablets, withdrawal syndrome , which leads to an increase in angina and an increase in blood pressure .

Biol tablets, instructions for use (method and dosage)

Biol tablets are recommended to be taken orally, in the morning, before or during breakfast, whole, with a small amount of water, once every 24 hours.

The instructions for use describe standard treatment regimens, however, in each individual case, the attending physician must select therapeutic regimens taking into account the heart rate and condition of the patient.

For arterial hypertension and coronary artery disease:

The daily dose is 5 mg, but can be increased to 10 mg.

Patients suffering from arterial hypertension and angina pectoris are prescribed at least 20 mg per day.

For CHF:

The minimum initial dose is 1.25 mg, which can be increased after analyzing the tolerability of the drug - first to 2.5 mg, then to 3.75 mg, 5 mg, 7.5 mg and a maximum after 2 weeks. – 10 mg. If therapy causes deterioration, it is better to consider reducing the dose.

Selection of dosage requires regular monitoring of blood pressure and heart rate . If the symptoms of CHF , arterial hypotension or bradycardia , it is necessary to select, first of all, standard doses of concomitant therapy and reduce the doses of the drug Biol, up to the discontinuation of treatment.

Biol

Monitoring of patients receiving treatment with the drug should include monitoring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), ECG, blood glucose levels in patients with diabetes (once every 4-5 months) . In elderly patients, it is recommended to monitor renal function (once every 4-5 months). After starting treatment for CHF at a dose of 1.25 mg, the patient should be examined within 4 hours (heart rate, blood pressure, ECG).

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50/min.

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

In approximately 20% of patients with angina, beta blockers are ineffective. The main causes are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100/min) and increased LV EDV, which impairs subendocardial blood flow. In smokers, the effectiveness of beta-blockers is lower.

Patients using contact lenses should take into account that during treatment the production of tear fluid may decrease.

When used in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if effective alpha-blockade is not previously achieved).

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

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

When taking clonidine concomitantly, it can be discontinued only a few days after discontinuation of the drug.

It is possible that the severity of the hypersensitivity reaction may increase and the absence of effect from usual doses of epinephrine against the background of a burdened allergic history.

If planned surgical treatment is necessary, the drug should be discontinued 48 hours before the start of general anesthesia. If the patient took the drug before surgery, he should select a drug for general anesthesia with minimal negative inotropic effect.

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

Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect arterial hypotension or bradycardia.

Patients with bronchospastic diseases can be prescribed cardioselective adrenergic blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs, but the dosage should be strictly monitored. An overdose is dangerous due to the development of bronchospasm.

If elderly patients develop increasing bradycardia (less than 50/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment . It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 3-4 days).

Use during pregnancy and lactation is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.

Treatment with bisoprolol should be discontinued before testing the levels of catecholamines, normetanephrine and vanillylmandelic acid in the blood and urine; antinuclear antibody titers.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Manifests itself in the form of symptoms such as:

arrhythmia;
severe bradycardia ;
AV block;
ventricular extrasystole;
decrease in blood pressure;
labored breathing;
bronchospasm;
development of acute heart failure, hypoglycemia , acrocyanosis ;
dizziness, fainting and convulsions.

First aid and symptomatic treatment measures

gastric lavage and taking adsorbents;
severe bradycardia is eliminated by intravenous administration of Atropine or, if necessary, a drug with a positive pronounced chronotropic effect;
temporarily install an artificial pacemaker;
a pronounced decrease in blood pressure can be corrected by intravenous administration of plasma replacement drugs and vasopressors ;
hypoglycemia requires intravenous administration of Glucagon or Dextrose ;
exacerbation of CHF - IV diuretics , possibly vasodilators ;
for AV blockade, β-adrenergic agonists are prescribed , for example, Epinephrine ;
when bronchospasm bronchodilators are used , incl. β-adrenergic agonists and/or Aminophylline .

Biol, 50 pcs., 5 mg, film-coated tablets