BIOL

Active material: Bisoprolol
When ATH: C07AB07
CCF: Beta₁-adrenoblokator
ICD-10 codes (testimony): I10, i20
When CSF: 01.01.01.02
Manufacturer: LEK d.d. (Slovenia)

Pharmaceutical form, composition and packaging

Pills, Film-coated light yellow, round, lenticular, with Phillips scored on one side and engraving “BIS 5” another; of presentations – white.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, corn starch, Croscarmellose sodium, magnesium stearate, Colloidal anhydrous silica.

The composition of the coating film: lactose monohydrate, gipromelloza, Titanium dioxide, MACROGOL-4000, dye iron (III) oxide yellow.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pills, Film-coated yellow color, round, lenticular, with Phillips scored on one side and engraving “BIS 10” another; of presentations – white.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, corn starch, Croscarmellose sodium, magnesium stearate, Colloidal anhydrous silica.

The composition of the coating film: lactose monohydrate, gipromelloza, Titanium dioxide, MACROGOL-4000, dye iron (III) oxide yellow, dye iron (III) Red oxide.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Selective beta₁-blocker without its own sympathomimetic activity. It has no membrane stabilizing action. It reduces plasma renin activity, reducing myocardial oxygen demand, It reduces the heart rate at rest and during exercise. It has hypotensive, antiarrhythmic and antianginal. Blocking in low doses β₁-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, It has a negative chrono, dromo-, ʙatmo- and inotropic effect. Oppressing conductivity and anxiety, slows AV-conduction. PR in the first 24 h of the drug increases (as a result of reciprocal increase in the activity of α-adrenergic stimulation and removal of β₂-adrenoreceptorov), which, through 1-3 d returns to the original, and prolonged the appointment of reduced.

The hypotensive effect is associated with a decrease in cardiac output, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (It is more important for patients with initial hypersecretion of renin), restoring sensitivity of aortic arch baroreceptors (not going to enhance their activity in response to the decline of HELL and the impact on the central nervous system). When hypertension effect after 2-5 days, stable gipotenzivny effect through 1-2 Months.

Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. At the expense of increasing end-diastolic pressure in the left ventricle and increased tensile ventricular muscle fibers can increase oxygen demand, 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, hypertension), decrease speed of spontaneous excitation of the sinus and jektopicheskogo pacemakers and slower AV-holding (mainly in the antegrade and, less, in retrograde direction through the AV-node) and on additional routes.

When used in high therapeutic doses, Unlike non-selective beta-blockers, It has a less pronounced effect on the organs, содержащие b₂-adrenoreceptory (pancreas, skeletal muscle, smooth muscle peripheral arteries, bronchial and uterine) and carbohydrate metabolism. No delays sodium ions in the body. With increasing doses of the above therapeutic exerts beta₂-adrenoceptor blocking action.

Pharmacokinetics

Absorption

Bisoprolol is almost completely absorbed from the digestive tract, meal no effect on absorption. Bioavailability – about 90%. T_max plasma – 2-4 hours after ingestion.

Distribution and allocation

The binding to plasma proteins – 26-33%. It is metabolized in the liver, metabolites of Bisoprolol have no pharmacological activity. The permeability of the BBB and placental barrier is low, in small amounts out of breast milk

Deduction

T_1/2 is 9-12 no, that makes it possible to apply medication 1 time / day. Report the news (50% in unchanged form), less 2% – through the intestine.

Testimony

- Arterial hypertension;

- CHD (prevention of angina attacks).

Dosage regimen

The tablets should be taken in the morning, regardless of the meal, do not chew, zapiwati few liquid

At hypertension and angina in all cases the dosage the doctor sets individually, given curves and the patient's condition. The initial daily dose is 5 mg (sometimes 2.5 mg) 1 time / day, if necessary, increase the dose to 10 mg 1 time / day. The maximum daily dose – 20 mg.

In patients with severe renal insufficiency (CC less than 20 ml / min) or with acute human liver the maximum daily dose should not exceed 10 mg.

Dose adjustment for elderly patients usually not required, However, some patients may not be the optimal dose 5 mg / day.

Side effect

Biol^® generally well tolerated. Side effects are mostly of a temporary nature, manifested in weak or moderate and usually do not require premature discontinuation of treatment.

CNS: fatigue, weakness, asthenia, dizziness, headache, sleep disorders, nightmares, mental disorders (depression), paresthesias in extremities (in patients with intermittent claudication and Raynaud's syndrome), impaired concentration, myasthenia, tremor.

On the part of the organ of vision: visual impairment, reduced secretion of tear fluid (to consider when wearing contact lenses), dryness and soreness of eyes, conjunctivitis.

Cardio-vascular system: orthostatic hypotension, chest pain, sinusovaya bradycardia, conduction disturbances infarction, AV блокада, withdrawal (increasing angina attacks, increased blood pressure), manifestation of vasospasm (increased violations of peripheral blood circulation, coldness of the lower extremities, Raynaud's syndrome), development (aggravation) the tide of chronic heart failure.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, dyspepsia, diarrhea, change in taste, abnormal liver function (symptoms of cholestasis), hepatitis, increased ALT, IS, bilirubin.

The respiratory system: nasal congestion, pharyngitis, rhinitis, sinusitis, cough, in predisposed patients – laringo- and bronchospasm.

For the skin: increased sweating, dermahemia, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms, alopecia.

From the hematopoietic system: thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: itching, rash, hives.

Other: increased sweating, backache, arthralgia, muscle aches, sexual dysfunction, dizurija, giperglikemiâ (in patients with non-insulin dependent diabetes mellitus), gipoglikemiâ (patients, receiving insulin), hypothyroid state, elevated triglycerides.

Contraindications

- Severe hypotension (systolic blood pressure less than 90 mm Hg. Art., especially in myocardial infarction);

- Acute heart failure, chronic cardiac insufficiency of the decompensation;

- Cardiogenic shock; collapse, pulmonary edema;

— AV-blockade II and III degrees (without installing the pacemaker);

- Sinoatrialynaya blockade;

sick sinus syndrome;

— expressed sinusova aetiology (HR less 50 u. / min);

-severe stage of human peripheral blood circulation, Raynaud's disease;

- Simultaneous MAO inhibitors (except MAO type B);

- Metabolic acidosis;

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

- Up to 18 years (efficacy and safety have not been established);

-hypersensitivity to bisoprololu and other components of the drug and other beta-adrenoblokatoram.

FROM caution:

- Severe hepatic impairment;

- Severe renal insufficiency;

- Thyrotoxicosis;

- Psoriasis;

- Myasthenia;

-AV- blockade degree I;

- Prinzmetal angina;

- Depression (incl. history);

- Pheochromocytoma (necessarily simultaneous use of Alfa-adrenoblokatorov);

- Diabetes;

— General anesthesia/surgery;

-severe allergic reactions (history).

Pregnancy and lactation

Application Of Biola^® Pregnancy may only, if the expected benefit to the mother outweighs the potential risk to the fetus.

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

Cautions

Should not abruptly interrupt treatment Biolom^® due to the risk of developing severe arrhythmias and myocardial infarction. The abolition of a gradually, reducing the dose to 25% every 3-4 day.

Control of patients, host Biol^®, It should include measurement of blood pressure and heart rate (at the beginning of treatment – daily, then – 1 once every 3-4 Months), ECG, determination of the level of glucose in patients with diabetes mellitus.

Older patients are recommended to monitor kidney function (1 once every 4-5 Months). It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 u. / min.

In the case of elderly patients increasing bradycardia (HR less 50 u. / min.), significant decrease in blood pressure (systolic blood pressure less than 100 mmHg.), AV-blockade, necessary to reduce the dose or stop treatment. Before treatment, it is recommended to carry out a study on respiratory function in patients with a history of bronholegochnym history.

In patients with possible risk of paradoxical feohromotsytoma hypertension (if not previously achieved effective alpha adrenoblockade).

Bisoprolol may mask the clinical signs of hyperthyroidism (eg, taxikardiju).

In diabetes Bisoprolol may mask tachycardia, induced hypoglycemia. In contrast, nonselective beta-adrenoblokatorov, virtually no increase insulin-induced hypoglycemia or delay recovery of the concentration of glucose in the blood to normal levels.

Sick, use contact lenses, We should take into account, that against the background of treatment may decrease the production of tear fluid.

While receiving clonidine his admission may be terminated only a few days after the lifting of Biola^®.

May increase the severity of hypersensitivity reactions and lack of effect of conventional doses of epinephrine to increase allergy background history. In the case of the need to conduct a surgical lifting drug spend for 48 h before general anesthesia. If a patient took Biol^® before the operation, preparation for general anesthesia should be compiled with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can eliminate I / atropine (1-2 mg).

Patients with bronhospasticheskimi diseases cardioselektivee adrenoblokatora could be appointed in case of intolerance and/or ineffectiveness other gipotenziveh funds; overdose is dangerous development of bronchospasm.

Drugs, reducing stocks catecholamines (incl. reserpine), may enhance the action of beta-blockers, so patients, taking such drug combinations, must be under the constant supervision of a physician to identify explicit reduction of hell or bradycardia.

It is recommended to discontinue therapy in the development of depression.

At smoking patients the effectiveness of beta-blockers lower.

Biol^® should repeal before the study content in the blood and urine Catecholamines, normetanephrine and vanilinmindalnoy acid; antinuclear antibodies.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: arrhythmia, ventricular premature beats, vыrazhennaya bradycardia, AV блокада, marked reduction in blood pressure, acute heart failure, gipoglikemiâ, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage and appointment of adsorbing drugs. Symptomatic therapy: at razvivšejsâ AV-blockade – in/in the introduction of atropine (1-2 mg), epinephrine, or staging a temporary pacemaker; when ventricular arrhythmia – lidokain (class A drugs I do not apply); with a decrease in blood pressure – the patient must be in the Trendelenburg position; if there are no signs of pulmonary edema – I / O solutions plazmozameschayuschie, the ineffectiveness – administration of epinephrine, dopamine, doʙutamina (to maintain the hronotropnogo and inotropnogo actions); Heart failure – cardiac glycosides, Diuretic, glucagon; with cramps – in / diazepam; with bronchospasm – beta₂-agonists by inhalation.

Drug Interactions

Allergens, used for immunotherapy (or allergen extracts for skin samples) the risk of severe systemic allergic reactions and Anaphylaxis in patients, receiving bisoprolol.

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers slow calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening of bradycardia, AV-blockade, heart failure and congestive heart failure.

Diuretic, klonidin, simpatolitiki, gidralazin, nifedipine and other gipotenzivee funds can lead to excessive reduction of HELL.

Iodized rentgencontrastnye funds for on/in the introduction increases the risk of anaphylactic reactions.

Phenytoin in in / in the introduction, drugs for inhalation general anesthesia (hydrocarbon derivatives) cardiodepressive increase the severity of the action and the probability of reduction of blood pressure.

Bisoprolol disguises adrenergic symptoms tireotoxicoza and hypoglycemia (eg, taxikardiju).

Lowers klirens lidocaine and xantinov (except difillina) and increases their concentration in blood plasma, especially in patients with initially increased clearance of theophylline under the influence of tobacco smoking.

Gipotenzivny effect NPVS weaken Bisoprolol (delay sodium ions and blockade of prostaglandin synthesis kidneys), SCS and estrogens (delay of sodium ions).

Extends the effect nedepoliarizuth miorelaksantov and antikoagulyannetary kumarinov effect.

Three- and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics funds reinforce oppression CNS.

Not recommended simultaneous application with MAO inhibitors due to a significant increase in the hypotensive action, a break in treatment between the reception of MAO inhibitors and bisoprolol must not be less than 14 days.

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

Sulfasalazine increases the concentration of bisoprolol in blood plasma.

Рифампицин укорачивает T_1/2 bisoprolol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be kept out of reach of children at a temperature of no higher than 25° c. Shelf life – 4 year. Do not use after the expiry date, on the package.