Biol, 5 mg 50 pcs.

Bisoprolol is a selective beta1-adrenoblocker with no sympathomimetic activity of its own and no membrane stabilizing effect. As with other beta1-adrenoblockers, the mechanism of action in arterial hypertension is unclear. At the same time, it is known that bisoprolol reduces plasma renin activity, decreases myocardial oxygen demand, and slows heart rate. It has hypotensive, antiarrhythmic and antianginal effects.

Blocking in low doses β1-adrenoreceptors of heart, decreases catecholamine-stimulated formation of cAMP from ATP, decreases intracellular flow of calcium ions, inhibits all heart functions, decreases AV conductivity and excitability. If the therapeutic dose is exceeded, it has a beta2-adrenoblocking effect. At the beginning of drug use, during the first 24 hours, HRPS increases (as a result of reciprocal increase of α-adrenoreceptors activity and elimination of β2-adrenoreceptors stimulation). After 1-3 days it returns to initial value, and during prolonged use it decreases.
Antihypertensive effect is related to the decrease of the blood minute volume, sympathetic stimulation of peripheral vessels, decrease of sympathoadrenal system activity (of greater importance for patients with initial renin hypersecretion), restoration of sensitivity in response to BP decrease and influence on CNS. In arterial hypertension the effect comes in 2-5 days, stable effect is noted in 1-2 months.

The antianginal effect is caused by decrease of myocardial oxygen demand as a result of decrease of contractility and other myocardial functions, prolongation of diastole, improvement of myocardial perfusion. By increasing left ventricular end-diastolic pressure and increasing ventricular muscle fiber stretch, oxygen demand may increase, especially in patients with chronic heart failure (CHF).

When used in medium therapeutic doses, unlike non-selective beta-adrenoblockers, it has less pronounced effect on organs containing β2-adrenoreceptors (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism. Does not cause retention of sodium ions in the body; intensity of atherogenic action does not differ from that of propranolol.

Pharmacokinetics:

Intake
Bisoprolol is almost completely absorbed from the gastrointestinal tract; absorption is not affected by meals. Bioavailability is about 90%. Tmax in plasma – 2-4 hours after oral administration.

Distribution and metabolism
Binding with plasma proteins is 26-33%. Metabolized in the liver, bisoprolol metabolites have no pharmacological activity. The permeability through the BBB and the placental barrier is low, in small amounts is excreted with breast milk. T1/2 is 9-12 hours, which makes it possible to use the drug once daily. It is excreted by the kidneys (50% unchanged), less than 2% – through the intestine.

Indications

– arterial hypertension;
– CHD: prevention of attacks of stable angina;
– Chronic heart failure (in combination therapy).

Active ingredient

Composition

Biol film-coated tablets are light yellow, round, biconvex, cross-ribbed on one side and engraved “BIS 5” on the other; white on the fracture.

1 tablet:

– bisoprolol hemifumarate 5 mg

Supplementary substances:

Cellulose microcrystalline,

calcium hydrophosphate,

corn starch,

br>

croscarmellose sodium,

magnesium stearate,

colloidal anhydrous silicon dioxide.

Composition of the film coating:

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

How to take, the dosage

The drug Biol® is taken orally, in the morning on an empty stomach, once a day and with some liquid, in the morning before, during or after breakfast. The tablets should not be chewed or crushed into a powder.
In all cases, the mode of administration and the dose are determined by the physician for each patient individually, especially taking into account the heart rate and the patient’s condition.

– Arterial hypertension and CHD
In case of arterial hypertension and CHD drug Biol® is used in dose of 5 mg once per day. If necessary the dose is increased up to 10 mg once daily.

In case of treatment of arterial hypertension and angina pectoris the maximum daily dose is 20 mg once daily.
– Chronic heart failure
Chronic heart failure treatment by Biol® requires obligatory titration phase and regular medical control.

The precondition for treatment with Biol® is stable chronic heart failure without aggravation signs. Treatment with Biol® chronic heart failure (CHF) is started according to the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e. the dose may be increased only if the previous dose was well tolerated.
To ensure appropriate titration process in the initial stages of treatment it is recommended to use the drug in lower doses.

The recommended starting dose is 1.25 mg (1/4 tablet of 5 mg) once daily. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg (1/2 tablet of 5 mg), 3.75 mg (3/4 tablet of 5 mg), 5 mg (1 tablet of Biol® 5 mg or 1/2 tablet of 10 mg), 7.5 mg (3/4 tablet of 10 mg) and 10 mg once daily at intervals of at least 2 or more weeks. If the increased dose is not well tolerated by the patient, the dose may be reduced.

The maximum daily dose for treatment of CHF is 10 mg once daily.

At the time of titration, regular monitoring of BP, HR and symptoms of CHF increase in severity is recommended. Worsening of CHF symptoms is possible from the first day of using the drug.

A temporary worsening of CHF course, arterial hypotension or bradycardia may occur during or after the titration phase. In this case, first of all, it is recommended to pay attention to the dose selection of concomitant standard therapy. It may also be necessary to temporarily decrease the dose of Biol® 5 mg or discontinue treatment.

After the patient’s condition has stabilized, the dose should be titrated again, or treatment should continue.

Hepatic or renal impairment

Mild to moderate hepatic or renal impairment usually does not require dose adjustment. In severe renal impairment (CKD less than 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 carried out with extreme caution.

Dose adjustment is not required in elderly patients.

To date there are not enough data regarding use of Biol® 5 mg in patients with CHF associated with diabetes mellitus type 1, severe renal and/or hepatic dysfunction, restrictive
cardiomyopathy, congenital heart disease or hemodynamically determined heart disease. There are also still insufficient data regarding patients with CHF with myocardial infarction within the last 3 months.

Interaction

Class I antiarrhythmic agents (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used simultaneously with bisoprolol may decrease AV conduction and myocardial contractility.
Class III antiarrhythmic agents (e.g. amiodarone) may increase AV conduction disorders.

The effects of beta-adrenoblockers for topical use (e.g. eye drops to treat glaucoma) may
increase the systemic effects of bisoprolol (BP reduction, heart rate slowing).

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

The concomitant use of Biol® with beta-adrenomimetics (e.g., isoprenaline, dobutamine) may decrease the effects of both drugs.

Combination of bisoprolol with adrenomimetics affecting beta- and alpha-adrenoreceptors (e.g. norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs arising from α-adrenoreceptors, leading to increased BP. Such interactions are more likely when using non-selective beta-adrenoblockers.

Mefloquine when used concomitantly with bisoprolol may increase the risk of 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 IV administration increase the risk of anaphylactic reactions.
Phenytoin by IV administration, agents for inhalation anesthesia (hydrocarbon derivatives) increase
the severity of cardiodepressive effects and the possibility of BP reduction.

The effectiveness of insulin and oral hypoglycemic agents may change with bisoprolol treatment (masks the symptoms of developing hypoglycemia: tachycardia and increased BP).

The clearance of lidocaine and xanthines (except theophylline) may be decreased due to possible increase of their plasma concentrations
especially in patients with initially increased clearance of theophylline due to smoking.
Hypotensive effect is weakened by NSAIDs (retention of sodium ions and blockade of prostaglandin synthesis by kidneys), GCS and estrogens (retention of sodium ions).

The 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, heart failure and heart failure.

Nifedipine can lead to a significant decrease in BP.

Diuretics, clonidine, sympatholytics, hydralazine, and other hypotensive agents may lead to excessive BP lowering.
The effects of nondepolarizing myorelaxants 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.

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

Unhydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.
Ergotamine increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the plasma concentration of bisoprolol.
Rifampicin shortens the T1/2 of bisoprolol.

Special Instructions

Biol® should not be stopped abruptly because of the danger of severe arrhythmias and myocardial infarction. Withdrawal should be done gradually, reducing the dose by 25% every 3 to 4 days.

Control of patients taking Biol® should include HR and BP measurements (daily at the beginning of therapy and then once every 3-4 months), ECG, determination of blood glucose concentration in diabetic patients (once every 4-5 months)

In elderly patients it is recommended to monitor renal function (once every 4-5 months).

The patient should be instructed on how to calculate heart rate and instructed to consult a physician if the heart rate is less than 50 bpm.

If elderly patients show increasing bradycardia (HR less than 50 beats/min), markedly decreased BP (systolic BP less than 100 mmHg), AV blockade, the dose should be reduced or the treatment should be stopped.

Before initiating treatment, it is recommended to perform an external respiratory function study in patients with a history of poor bronchopulmonary function.

Patients who wear contact lenses should note that there may be a decrease in tear fluid production during treatment with the drug.

In patients with pheochromocytoma, there is a risk of paradoxical arterial hypertension when using Biol® (if effective blockade of the alpha-adrenoreceptors has not been previously achieved).

In hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (e.g.,
tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because it may exacerbate the symptoms.
In diabetes mellitus, bisoprololol may mask the tachycardia caused by hypoglycemia. Unlike non-selective beta-adrenoblockers, it practically does not increase insulin-induced hypoglycemia and does not delay the recovery of blood glucose concentration to normal levels.

In case of simultaneous use of clonidine its use can be stopped only after several days after discontinuation of the drug Biol®.
It is possible that the severity of hypersensitivity reactions will increase and the conventional doses of epinephrine will have no effect with a history of severe allergy.

In case of necessity of surgical intervention the drug is withdrawn 48 hours prior to the beginning of general anesthesia. If the patient has taken the drug prior to surgical intervention, the drug for general anesthesia should be selected with minimal negative inotropic effect.

The reciprocal activation of the vagus nerve can be eliminated by IV atropine (1-2 mg).

Drugs that reduce catecholamine stores (including reserpine) can potentiate the effects of beta-adrenoblockers, so patients taking these combinations of drugs should be monitored closely by a physician for signs of marked BP reduction or bradycardia.

Patients with bronchospastic disorders may be prescribed cardioselective beta-
adrenoblockers with caution if other hypotensive agents are intolerant and/or ineffective. Against the background of taking
beta-adrenoblockers 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 patients show increasing bradycardia (HR less than 50 beats/min), significant decrease of BP (systolic BP less than 100 mm Hg), AV blockade, the dose should be reduced or the treatment should be stopped.

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

The treatment should not be stopped abruptly because of the risk of severe arrhythmias and myocardial infarction. The drug should be withdrawn gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% every 3 to 4 days).

The drug should be discontinued before blood and urine concentrations of catecholamines, normetanephrine, vanillin acid, and antinuclear antibody titers are tested.

The efficacy of beta-adrenoblockers is lower in smoking patients.

Impact on driving and operating machinery

When treating with Biol® care should be taken with driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

– Acute heart failure and chronic heart failure in the decompensation stage, requiring inotropic therapy;
– cardiogenic shock;
– collapse;
– AV-blockade of II and III degree (without pacemaker);
– sinoatrial block;
– sinus node weakness syndrome;
– bradycardia (heart rate before the treatment less than 50 beats/min).
– arterial hypotension (systolic BP less than 90 mm Hg);
– arterial hypotension (systolic BP less than 90 mm Hg);
– cardiopulmonary hypertension.);
– cardiomegaly (without signs of heart failure);
– severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD) in anamnesis;
– significant disorders of peripheral circulation;
– Raynaud’s syndrome;
– metabolic acidosis;
– Pheochromocytoma (without simultaneous use of alpha-adrenoblockers);
– concomitant use of floktafenine and sultopride;
– age under 18 years (effectiveness and safety has not been established);
– hypersensitivity to components of the preparation Biol and to other beta-adrenoblockers.
With caution:
– conducting desensitizing therapy;
– hyperthyroidism;
– type 1 diabetes mellitus and diabetes with significant fluctuations in blood glucose concentrations;
– significant renal insufficiency (CK less than 20 ml/min);
– significant liver function abnormalities;
– psoriasis;
–
– Degree I AV block;
– Prinzmetal angina;
– Restrictive cardiomyopathy;
– Congenital heart disease or heart valve defect with significant hemodynamic disorders;
– Chronic heart failure with myocardial infarction during the last 3 months;
– Depression (including in anamnesis).Pheochromocytoma (concomitant use of alpha-adrenoblockers is obligatory);
– strict diet.

Side effects

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

Cardiovascular system: very often – decreased HR (bradycardia, especially in patients with CHF), sensation of palpitations; often – marked decrease in BP (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulation disorders, feeling of cold in the extremities (paresthesias); infrequent – AV conduction disorders (up to complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, worsening of CHF with development of peripheral edema (edema of ankles, feet, dyspnea), chest pain.

Nervous system disorders: frequently – dizziness, headache, asthenia, fatigue, sleep disturbances, depression, anxiety; rarely – mental confusion or short-term memory loss, nightmares, hallucinations, myasthenia, tremor, muscle cramps. Usually these phenomena are mild and usually go away within 1-2 weeks after the start of treatment.

Senses: rare – visual disturbances, decreased tear production (should be considered when wearing contact lenses), tinnitus, decreased hearing, ear pain; very rare – dry and painful eyes, conjunctivitis, taste disorders.

Respiratory system disorders: infrequent – bronchospasm in patients with bronchial asthma or obstructive airways disease; rare – allergic rhinitis; nasal congestion.

The digestive system: frequently – nausea, vomiting, diarrhea, constipation, dry mouth, abdominal pain; rarely – hepatitis, increased liver enzymes activity (ALT, AST), increased bilirubin concentration, change in taste.

Muscular system disorders: infrequent – arthralgia, back pain.

Urogenital system disorders: very rarely – impaired potency, decreased libido.

Laboratory disorders: rare – increased concentration of triglycerides in the blood; in some cases – thrombocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rare – skin itching, rash, urticaria.

Skin disorders: rare – increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions; very rare – alopecia; beta-adrenoblockers may worsen psoriasis.

Others: “withdrawal” syndrome (increased frequency of angina pectoris attacks, increased BP).

Overdose

Symptoms: arrhythmia, ventricular extrasystole, marked bradycardia, AV block, marked BP decrease, acute heart failure, hypoglycemia, acrocyanosis, difficulty in breathing, bronchospasm, dizziness, fainting, seizures.

Treatment: first of all the drug administration should be stopped, the stomach should be flushed, adsorptive agents should be taken, symptomatic therapy should be carried out.

In case of marked bradycardia – intravenous injection of atropine. If the effect is insufficient, a drug with a positive chronotropic effect may be administered with caution. Sometimes a temporary artificial pacemaker may be required.

In case of pronounced BP decrease – intravenous administration of plasma exchange solutions and vasopressors.

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

In AV blockade: patients should be constantly monitored,
and treated with beta-adrenomimetics such as epinephrine. If necessary, an artificial pacemaker should be placed.

In exacerbation of CHF – intravenous administration of diuretics, drugs with positive inotropic effect, and vasodilators.
In case of bronchospasm – administration of bronchodilators, including beta2-adrenomimetics and/or aminophylline.

Pregnancy use

Bisoprolol has no direct cytotoxic, mutagenic, or teratogenic effects, but it has pharmacological effects that may have harmful effects on pregnancy and/or the fetus, or on the newborn. Typically, beta-adrenoblockers decrease placental perfusion, which leads to fetal growth retardation, intrauterine fetal death, miscarriage, or preterm birth. The fetus and the newborn baby may have pathological reactions such as intrauterine developmental delay, hypoglycemia, and bradycardia.

The drug Biol® should not be used during pregnancy; the use is possible if the benefit to the mother exceeds the risk of side effects in the fetus and/or child.

When treatment with Biol® is considered necessary, the blood flow in the placenta and uterus should be monitored and the growth and development of the unborn child should be monitored, and in case of adverse events regarding pregnancy and/or fetus, alternative therapies should be taken. The newborn should be carefully examined after delivery. Symptoms of hypoglycemia and bradycardia usually occur within the first 3 days of life.

There is no evidence of bisoprolol penetration into breast milk. Therefore, the use of Biol® is not recommended to women during lactation. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Similarities