Bisoprol 5 mg tablets # 50 *

Bisoprolol instructions for use

Composition:

active ingredient: bisoprolol; 1 tablet contains bisoprolol fumarate in terms of 100% substance 2.5 mg, 5 mg, 10 mg;
auxiliary substances (tablets of 2.5 mg): microcrystalline cellulose, calcium hydrophosphate, crospovidone, silicon dioxide colloidal anhydrous, magnesium stearate;

auxiliary substances (tablets of 5 mg and 10 mg): lactose monohydrate, microcrystalline cellulose, calcium hydrophosphate, crospovidone, silicon dioxide colloidal anhydrous, yellow sunset FCF (E 110), magnesium stearate.

Dosage form

Pills.

Basic physical and chemical properties:

tablets of 2.5 mg white, round with a biconvex surface, with or without risk. On the surface of tablets, marble is allowed;

tablets of 5 mg round shape with biconvex surface, pale pink, with or without risk. On the surface of tablets are allowed inclusions;

tablets of 10 mg round shape with a flat surface, with a facet and a risk, pale pink. On the surface of the tablets, inclusions are allowed.

Pharmacotherapeutic group

Selective blockers of β-adrenergic receptors. Code ATX C07A B07.

Pharmacological properties

Pharmacodynamics.

Bisoprolol is a highly selective ß1-blocker. When used in therapeutic doses, it has no internal sympathomimetic activity and clinically expressed membrane-stabilizing properties. Has antianginal and hypotensive effect. Reduces myocardial oxygen demand by reducing heart rate and reducing cardiac output and lowering blood pressure, increasing myocardial oxygen supply by decreasing end-diastolic pressure and diastole lengthening. The drug has a very low affinity for the ß2-receptors of the smooth muscles of the bronchi and vessels, as well as for the ß2-receptors of the endocrine system.

The maximum effect of bisoprolol occurs 3-4 hours after admission. The half-life of plasma is 10-12 hours, which leads to a 24-hour effectiveness after a single dose. The maximum antihypertensive effect is achieved after 2 weeks of admission.

Pharmacokinetics.

Suction. After ingestion Bisoprol is well adsorbed from the gastrointestinal tract. Bioavailability is about 90% after oral administration and is not dependent on food intake. The pharmacokinetics of bisoprolol and the concentration in the blood plasma are linear in the dose range from 5 mg to 20 mg. The maximum concentration in the blood plasma (C max) is achieved in 2-3 hours.

Distribution. The volume of distribution is 3.5 l / kg. Binding to plasma proteins is about 30%.

Metabolism and excretion. Bisoprolol is excreted from the body in two ways: 50% biotransformed in the liver with the formation of inactive metabolites and excreted by the kidneys, 50% excreted by the kidneys in unchanged form. In vitro studies using human liver microsomes have shown that bisoprolol is metabolized with CYP3A4 (~ 95%), CYP2D6 plays only a small role. The total clearance of bisoprolol is 15 l / h. The half-life is 10-12 hours.

Indications

• Arterial hypertension;
• ischemic heart disease (angina);
• chronic heart failure with systolic dysfunction of the left ventricle, in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Contraindications

• Acute heart failure or heart failure in a state of decompensation, requiring inotropic therapy;
• cardiogenic shock;
• atrioventricular blockade of II and III degree (except for those in patients with an artificial pacemaker);
• syndrome of weakness of the sinus node;
• pronounced sinoatrial block;
• symptomatic bradycardia;
• symptomatic arterial hypotension;
• severe form of bronchial asthma or severe chronic obstructive pulmonary disease;
• late stages of peripheral circulation or Raynaud's disease;
• untreated pheochromocytoma;
• metabolic acidosis;
• hypersensitivity to bisoprolol or other components of the drug.

Interaction with other drugs and other interactions

Combinations that are not recommended for use.

Treatment of chronic heart failure.

- Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): a negative effect on atrioventricular conduction and inotropic myocardial function.

All indications.

- Calcium antagonists like verapamil, to a lesser extent - diltiazema: a negative effect on the contractile function of the myocardium and atrioventricular conductivity. Intravenous administration of verapamil can lead to severe arterial hypotension and atrioventricular blockade in patients who take ß-blockers.

- Hypotensive drugs with a central mechanism of action (clonidine, methyldopa, moxinidine, rilmenidine): may lead to worsening of heart failure. With combined therapy, sudden withdrawal of these drugs can increase the risk of reflex hypertension.

For ombination, which should be used with caution.

Treatment of arterial hypertension or coronary heart disease (angina pectoris).

- Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): may increase the negative effect on atrioventricular conduction and inotropic myocardial function.

All indications.

- Calcium antagonists such as dihydropyridine (eg nifedipine, felodipine, amlodipine): may increase the risk of arterial hypotension. The possibility of increasing the negative effect on the inotropic function of the myocardium in patients with heart failure is not ruled out.

- Antiarrhythmic drugs of the III class (for example, amiodarone): may increase the negative effect on atrioventricular conductivity.

- ß-blockers of local action (for example, those contained in eye drops for the treatment of glaucoma): the action of bisoprolol may be enhanced.

- Parasympatomimetics: the time of atrioventricular conduction may increase and the risk of bradycardia may increase.

- Insulin and oral hypoglycemic agents: the effect of these drugs is enhanced. Symptoms of hypoglycemia can be masked. This interaction is more likely when using non-selective β-blockers.

- Means for anesthesia: the risk of oppression of myocardial function increases and arterial hypotension arises.

- Cardiac glycosides (digitalis preparations): can reduce the heart rate, increase the time of atrioventricular conduction.

- Non-steroidal anti-inflammatory drugs (NSAIDs): can reduce the hypotensive effect of bisoprolol.

- ß-sympathomimetics (eg, isoprenaline, dobutamine): use in combination with the drug Bisoprol can lead to a decrease in the therapeutic effect of both agents.

- Sympathomimetics, which activate α- and ß-adrenergic receptors (for example, adrenaline, norepinephrine): increase blood pressure. This interaction is more likely when using non-selective β-blockers.

- Tricyclic antidepressants, barbiturates, phenothiazine increase the risk of arterial hypotension.

Combinations that should be considered.

Mefloquine: may increase the risk of bradycardia.

- MAO inhibitors (except for MAO type B inhibitors): increase the antihypertensive effect of ß-blockers. There is a risk of developing a hypertensive crisis.

Application features

The drug should be used with caution to patients under such conditions:

- bronchospasm (with bronchial asthma or chronic obstructive pulmonary diseases);

- diabetes mellitus with sharp fluctuations in blood glucose levels, while the symptoms of hypoglycemia (tachycardia, palpitation, sweating) can be hidden;

- strict diet;

- Desensitizing therapy;

- atrioventricular blockade of the 1st degree;

- Prinzmetal angina;

- Violations of peripheral circulation (at the beginning of therapy, it is possible to increase complaints);

General anesthesia.

It is necessary to warn the doctor-anesthesiologist about the admission of blockers of β-adrenergic receptors. In patients with general anesthesia, the use of β-blockers reduces the incidence of arrhythmia and myocardial ischemia during anesthesia, intubation and postoperative period. It is recommended to continue the use of β-blockers during the intraoperative period. An anesthesiologist must take into account the potential interaction with other drugs that can lead to bradyarrhythmia, reflex tachycardia and a decrease in the capacity of the reflex mechanism to compensate for the pressure drop. In the event of the cancellation of bisoprolol before surgery, the dose should be gradually reduced and discontinued 48 hours before general anesthesia.

At present, there is no sufficient therapeutic experience in the treatment of chronic heart failure in patients with such diseases and pathological conditions: Type I diabetes mellitus, severe renal dysfunction, severe liver dysfunction, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant valvular heart disease acquired, myocardial infarction myocardium for the last 3 months.

Combinations of bisoprolol with calcium antagonists such as verapamil or diltiazem, with class I antiarrhythmic drugs and with central-action antihypertensives are not recommended (see "Interactions with Other Drugs and Other Interactions").

In bronchial asthma or other chronic obstructive pulmonary diseases, concomitant therapy with bronchodilators is indicated. In some cases, patients receiving bronchial asthma may require higher doses of ß2-sympathomimetics due to increased airway tone.

Like other ß-blockers, bisoprolol can increase sensitivity to allergens and enhance anaphylactic reactions. In such cases, treatment with epinephrine does not always produce a positive therapeutic effect.

Patients with psoriasis (including anamnesis) should be treated with β-blockers (eg, bisoprolol) after careful study of the benefit / risk ratio.

Patients with pheochromocytoma are prescribed Bisoprol only on the background of preliminary therapy with α-blockers.Symptoms of thyrotoxicosis can be masked against the background of taking the drug. With the use of the drug Bisoprol, a positive result is possible with doping control.

At the beginning of treatment, the drug should be monitored regularly.

If necessary, therapy with the drug should be completed slowly, gradually reducing the dose.

Treatment with Bisoprol should not be stopped suddenly if there is no clear indication for this.

The composition of bisoprol 5 mg and 10 mg tablets includes lactose, so this drug is not recommended for patients with a rare congenital intolerance to galactose, with a deficiency of lactase or glucose-galactose malabsorption syndrome.

Use during pregnancy or lactation

During pregnancy, the drug is used only when the expected benefit to the mother exceeds the potential risk to the fetus.As a rule, ß-adrenoblockers reduce blood flow in the placenta and can affect fetal development. If treatment with a β-blocker is necessary, it is desirable that it is a β1-selective blocker. It is necessary to monitor utero-placental blood flow and fetal growth.

After delivery, the newborn should be carefully monitored. Symptoms of hypoglycemia and bradycardia can be expected within the first 3 days.

Data on the excretion of bisoprolol in breast milk or safety of influence on infants is not available, so it is not recommended to use Bisoprol during breastfeeding.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

In some cases, the drug may affect the ability to drive vehicles or work with complex mechanisms. Particular attention must be given at the beginning of treatment, with a change in the dose of the drug or in the interaction with alcohol.

Dosing and Administration

Tablets should be taken without chewing, in the morning on an empty stomach or during breakfast, washed down with a small amount of water.

Arterial hypertension; ischemic heart disease (angina).

The recommended dose is 5 mg per day. In the case of moderate hypertension (diastolic pressure up to 105 mmHg) a dose of 2.5 mg is appropriate.

If necessary, the daily dose can be increased to 10 mg per day. The maximum recommended dose is 20 mg per day.

The change and correction of the dose is determined by the physician individually, depending on the patient's condition.

Bisoprol must be used with caution in patients with hypertension or ischemic heart disease, which is accompanied by heart failure.

Chronic heart failure with systolic dysfunction of the left ventricle in combination with ACE inhibitors, diuretics, if necessary - cardiac glycosides.

Standard therapy for chronic heart failure: ACE inhibitors (or angiotensin receptor blockers with intolerance to ACE inhibitors), β-adrenoreceptor blockers, diuretics and, if necessary, cardiac glycosides.

Bisoprol is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.

Treatment of chronic heart failure Bisoprol begins in accordance with the following scheme of titration and can be corrected depending on the individual reactions of the organism (see Table 1).

- 1,25 mg * of bisoprolol fumarate 1 time per day for 1 week, increasing to

- 2.5 mg of bisoprolol fumarate 1 time per day for the next 1 week, increasing to

- 3.75 mg * of bisoprolol fumarate once a day for the next 1 week, increasing to

- 5 mg of bisoprolol fumarate once a day for the next 4 weeks, increasing to

- 7.5 mg * of bisoprolol fumarate once a day for the next 4 weeks, increasing to

- 10 mg of bisoprolol fumarate once a day as maintenance therapy.

Weeks of titration The dose of titration (mg)

1st week 1.25 *

2nd week 2.5 *

3rd week 3.75 *

4th week 5

5th week 5

6th week 5

7th week 5

8th week 7.5 *

9th week 7.5 *

10th week 7.5 *

11th week 7.5 *

12th week 10

* Use bisoprolol with the possibility of such dosing.

The maximum recommended dose of bisoprolol fumarate is 10 mg 1 time per day.

At the beginning of treatment of persistent chronic insufficiency, regular monitoring is necessary. During the titration phase, monitoring of vital signs (blood pressure, heart rate) and symptoms of progression of heart failure is necessary.

Modification of treatment.

If arterial hypotension or bradycardia worsens during or after the titration phase, heart failure is observed, it is recommended that the dosage be corrected: a temporary reduction in the dose of bisoprolol or, possibly, suspension of treatment may be required. After stabilization of the patient's condition, continue treatment with the drug.

The course of treatment with Bisoprol is long.

Do not stop treatment suddenly and change the recommended dose without consulting a doctor, as this can lead to a deterioration in the patient's condition. If necessary, treatment with the drug should be completed slowly, gradually reducing the dose.

Patients with hepatic and renal insufficiency.

Arterial hypertension; cardiac ischemia. For patients with a malfunction of the liver or kidneys of mild and moderate severity, dosing is usually not necessary. For patients with severe renal insufficiency (creatinine clearance less than 20 ml / min) and for patients with severe liver failure, the dose should not exceed a daily dose of 10 mg.

Chronic heart failure. There is no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure concomitantly with impaired hepatic and / or renal function, so it is necessary to increase the dose with caution.

Older patients do not require a dose adjustment.

Children.

Clinical data on the efficacy and safety of the drug for the treatment of children are absent.

Overdose

The most frequent signs of drug overdose are bradycardia, arterial hypotension, acute heart failure, hypoglycemia and bronchospasm. There is a wide variability in individual sensitivity to a single high dose of bisoprolol, patients with heart failure may be more sensitive to the drug.

In case of an overdose, cases of development of atrioventricular blockade of grade III and dizziness were also recorded.

In case of an overdose, immediately consult a doctor.

Depending on the degree of overdose, stop treatment with the drug and conduct supportive and symptomatic therapy.There is limited evidence that bisoprolol is difficult to dialysis.

With bradycardia: intravenous administration of atropine. If there is no reaction, caution is taken with isoprenaline or another drug with a positive chronotropic effect. In exceptional cases, introduce an artificial pacemaker.

If hypotension: receiving vasoconstrictors, intravenous administration of glucagon.

In atrioventricular block II and III degree: administering an infusion of isoprenaline; if necessary - pacing.

During exacerbation of chronic heart failure: intravenous administration of diuretics and vasodilators.

When bronchospasm: bronchodilators (e.g., isoprenaline), β2-adrenoceptor agonists and / or aminophylline.

When hypoglycemia: intravenous glucose.

Adverse Reactions

Of the heart: bradycardia, signs of worsening of heart failure (in patients with chronic heart failure, hypertension or ischemic heart disease); atrioventricular conduction disorders, bradycardia (in patients with hypertension or ischemic heart disease).

From the nervous system: dizziness *, headache *, syncope.

From the side of view: reduction slezovydeleniya (you need to consider when wearing contact lenses), conjunctivitis.

On the part of hearing: hearing impairment.

The respiratory system: bronchospasm in patients with asthma and a history of chronic obstructive airways disease; allergic rhinitis.

On the part of the digestive tract: nausea, vomiting, diarrhea, constipation.

Of the skin and connective tissues: hypersensitivity reactions - itching, redness, rash, alopecia. In the treatment of ß-blockers may experience deterioration in patients with psoriasis in the form of psoriatic lesions.

On the part of the musculoskeletal system: muscle weakness, cramps.

Liver: Hepatitis.

On the part of the circulatory system: the feeling of cold or numbness in the extremities, hypotension (especially in patients with heart failure), orthostatic hypotension.

Reproductive system: violation of potency.

Psychiatric disorders: depression, sleep disturbances, nightmares, hallucinations.

Laboratory indicators: increase in blood triglycerides, elevated liver enzymes in serum (AST, ALT).

General disorders: asthenia (patients with congestive heart failure), fatigue *, asthenia (patients with arterial hypertension or ischemic heart disease).

* Applies only to patients with hypertension or ischemic heart disease. These symptoms usually occur early in treatment, are mild and disappear within the first 1-2 weeks.

In case of any side effects or adverse reactions should inform your doctor immediately.

Shelf life

2 years (2.5 mg tablets). 3 years (tablets 5 mg and 10 mg). Do not use the product after the expiration date printed on the package.

Storage conditions

Stored in original package at a temperature not higher than 25 ° C. Keep out of the reach of children.

Packaging

10 tablets in a blister pack. 2, 3 or 5 blisters in a pack.

Category of leave

On prescription.