Bisoprolol-Astrapharm tablets 10 mg blister No. 30

Translation of the instructions can be

Instruction

For medical use of the medicinal product

Bisoprolol-Astrapharm

(Bisoprolol-astrapharm)

Composition:

Active ingredient: bisoprolol;

1 tablet contains bisoprolol fumarate 5 mg or 10 mg;

Excipients: lactose monohydrate; croscarmellose sodium; microcrystalline cellulose; magnesium stearate.

Dosage form.

Pills.

Main physicochemical properties: white tablets, flat-cylindrical in shape with beveled edges and a score on one side.

Pharmacotherapeutic group.

Selective β-adrenergic blockers.

ATX code C07A B07.

Pharmacological properties.

Pharmacodynamics.

Bisoprolol is highly selective for β 1 -adrenoreceptors. It has no intrinsic sympathomimetic activity and clinically pronounced membrane-stabilizing properties. The drug has a very low affinity for β 2 -receptors of the smooth muscles of the bronchi and blood vessels, as well as for β 2 -receptors involved in methylation regulation. Thus, bisoprolol does not affect airway resistance and β 2 -mediated methylation effects. The selectivity of bisoprolol for β 1 -adrenoreceptors extends beyond the therapeutic dose range.

Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of bisoprolol occurs 3-4 hours after administration. The half-life from blood plasma is 10-12 hours, which results in a 24-hour efficacy after a single dose of the drug. The maximum antihypertensive effect is achieved after 2 weeks of administration.

In intensive therapy in patients with coronary heart disease without chronic heart failure, bisoprolol reduces cardiac output and myocardial oxygen demand by reducing heart rate and stroke volume. With prolonged therapy, increased peripheral resistance decreases. The antihypertensive effect of β-blockers is also based on the mechanism of action of reducing plasma renin activity.

Bisoprolol inhibits the response of sympathoadrenergic activity by blocking cardio-β1 receptors. This leads to a slowdown in heart rate and a decrease in myocardial contractile function, which causes a decrease in myocardial oxygen demand. Due to this, the desired effect is achieved in patients with angina pectoris and ischemic heart disease.

Pharmacokinetics.

After oral administration, more than 90% of bisoprolol is absorbed from the gastrointestinal tract. Absorption is independent of food intake. The first-pass effect is insignificant, which contributes to high bioavailability - approximately 90%. Binding to plasma proteins is approximately 30%. The volume of distribution is 3.5 l/kg.

Bisoprolol is excreted from the body in two ways: approximately 50% is metabolized in the liver to form inactive metabolites and excreted by the kidneys, 50% is excreted by the kidneys unchanged. The total clearance of bisoprolol is 15 l / h. Due to the long half-life (10-12 hours) the drug retains a therapeutic effect for 24 hours when used once a day.

Due to the approximately equal participation of the kidneys and liver in the excretion of this drug, patients with renal or hepatic insufficiency do not need to adjust the dose. The kinetics of bisoprolol are linear and do not depend on age.

Clinical characteristics.

Indication.

Arterial hypertension.

Ischemic heart disease (angina pectoris).

Chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.

Contraindication.

- hypersensitivity to bisoprolol or to other components of the drug;

- acute heart failure or heart failure in a state of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- atrioventricular block of the II and III degree (except in patients with an artificial pacemaker);

- sick sinus syndrome;

- sinoatrial block;

- symptomatic bradycardia;

- symptomatic arterial hypotension;

- severe bronchial asthma or severe chronic obstructive pulmonary disease;

- late stages of peripheral circulatory disorders or Raynaud's disease;

- metabolic acidosis;

Interaction with other drugs and other types of interactions.

Combinations that are not recommended for use.

Treatment of chronic heart failure

Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone). Potentiation of the effect on atrioventricular conduction and increased negative inotropic effect is possible.

all evidence

Calcium antagonists (verapamil group, to a lesser extent diltiazem). Negative effect on myocardial contractile function and atrioventricular conduction. Intravenous administration of verapamil in patients taking β-blockers can lead to severe hypotension and atrioventricular block.

Combinations that should be used with caution.

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

Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone). Potentiation of the atrioventricular conduction effect and increased negative inotropic effect is possible.

all evidence

Dihydropyridine calcium antagonists (e.g. nifedipine, felodipine, amlodipine). Possible increased risk of arterial hypotension. The possibility of increased negative effects on myocardial inotropic function in patients with heart failure cannot be excluded.

Class III antiarrhythmic drugs (e.g. amiodarone). Potentiation of the effect on atrioventricular conduction is possible.

Topical β-blockers (e.g. those contained in eye drops for the treatment of glaucoma). Systemic effects of bisoprolol may be enhanced.

Parasympathomimetics: Possible increase in atrioventricular conduction time and increased risk of bradycardia.

Insulin and oral hypoglycemic agents. Increased hypoglycemic effect. Blockade of β-adrenergic receptors may mask symptoms of hypoglycemia.

Anesthetics: Increased risk of myocardial depression and hypotension (see section "Special warnings and precautions for use").

Cardiac glycosides. Decreased heart rate, increased atrioventricular conduction time.

Nonsteroidal anti-inflammatory drugs (NSAIDs): May weaken the hypotensive effect of bisoprolol.

β-sympathomimetics (e.g. orciprenaline, isoprenaline, dobutamine). Use in combination with bisoprolol may lead to a decrease in the therapeutic effect of both agents. High doses of adrenaline may be required for the treatment of allergic reactions.

Sympathomimetics that activate α- and β-adrenergic receptors (e.g., adrenaline, noradrenaline). A vasoconstrictor effect mediated through α-adrenergic receptors may occur, leading to increased blood pressure and increased intermittent claudication. This interaction is most likely with nonselective β-blockers.

When used together with antihypertensive agents and agents with hypotensive effects (e.g. tricyclic antidepressants, barbiturates, phenothiazines), the risk of hypotension may be increased.

Possible combinations.

Mefloquine: Possible increased risk of bradycardia.

MAO inhibitors (except MAO inhibitors type B). Increased hypotensive effect of β-blockers, but there is a risk of developing hypertensive crisis.

Rifampicin: Slight reduction in the half-life of bisoprolol, possibly due to induction of liver enzymes that metabolize drugs. Usually no dose adjustment is required.

Ergotamine derivatives. Exacerbation of peripheral circulatory disorders.

Application features.

Treatment of stable chronic heart failure with bisoprolol should begin with a titration phase.

In patients with coronary heart disease, treatment should not be stopped abruptly unless absolutely necessary, as this may lead to transient deterioration of the condition. Initiation and discontinuation of bisoprolol treatment requires regular monitoring.

To date, there is insufficient therapeutic experience in the treatment of chronic heart failure in patients with the following diseases and pathological conditions: type 1 diabetes mellitus, severe renal dysfunction, severe hepatic dysfunction, restrictive cardiomyopathy, congenital heart defects, hemodynamically significant valvular heart defects, myocardial infarction within the last 3 months.

The drug should be used with caution in patients with the following conditions:

This medicine contains lactose. Patients with known intolerance to some sugars should consult their doctor before taking this medicine.

Combinations of bisoprolol with calcium antagonists of the verapamil or diltiazem group, with class I antiarrhythmic drugs and with centrally acting antihypertensive agents are not recommended (see section "Interaction with other medicinal products and other types of interactions").

Although cardioselective β-blockers (β 1) have less effect on lung function than non-selective β-blockers, their use, like all β-blockers, should be avoided in obstructive airway diseases unless there are compelling reasons for therapy. If necessary, bisoprolol should be used with caution. In patients with obstructive airway diseases, bisoprolol treatment should be started at the lowest possible dose and the patient should be monitored for new symptoms (e.g. dyspnea, exercise intolerance, cough).

In bronchial asthma or other chronic obstructive pulmonary diseases, concomitant therapy with bronchodilators is indicated. In some cases, while taking the drug, patients with bronchial asthma may require higher doses of β 2 -sympathomimetics due to increased airway resistance.

Patients with psoriasis (including a history of psoriasis) should be prescribed β-blockers (e.g. bisoprolol) after careful benefit/risk assessment.

Patients with pheochromocytoma should be prescribed bisoprolol only after treatment with α-adrenergic blockers.

Symptoms of thyrotoxicosis may be masked by bisoprolol.

When using bisoprolol, a positive result may be noted during doping control.

Use during pregnancy or breastfeeding.

Pregnancy.

Bisoprolol has pharmacological properties that may cause harmful effects on the course of pregnancy and/or the development of the fetus/newborn. As a rule, β-blockers reduce placental blood flow, which can cause intrauterine growth retardation, intrauterine fetal death, spontaneous abortion or premature birth. Adverse effects in the fetus and newborn (e.g. hypoglycemia, bradycardia) may develop. If treatment with β-blockers is necessary, it is preferable that it be a β 1 selective adrenoblocker.

During pregnancy, the drug can be used only if the expected benefit to the mother outweighs the potential risk to the fetus. It is necessary to monitor uteroplacental blood flow and fetal growth. In case of harmful effects on the course of pregnancy or the fetus, alternative treatment should be considered.

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

Breastfeeding period.

There is no data on the excretion of bisoprolol into breast milk, therefore it is not recommended to use Bisoprolol-Astrapharm during breastfeeding.

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

It is known that in patients with coronary heart disease, bisoprolol does not affect the ability to drive or use other mechanisms.

In some cases, the drug may affect the ability to drive or operate complex mechanisms. Particular attention should be paid at the beginning of treatment, when changing the dose of the drug or when interacting with alcohol.

Method of administration and doses.

Bisoprolol-Astrapharm tablets should be swallowed without chewing, in the morning on an empty stomach, during or after breakfast, with a small amount of liquid.

Arterial hypertension; ischemic heart disease (angina pectoris).

Treatment should be started gradually with low doses and then increased. The recommended dose is 5 mg (1 tablet of Bisoprolol-Astrafarm 5 mg) per day. For mild hypertension (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg is suitable.

If necessary, the daily dose can be increased to 10 mg (1 tablet of Bisoprolol-Astrafarm 10 mg) per day. Further dose increases are justified only in exceptional cases. The maximum recommended dose is 20 mg per day.

Dose adjustment is determined by the doctor individually, depending on the pulse rate and therapeutic benefit.

Chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.

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

Bisoprolol-Astrapharm is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.

Therapy should be carried out by a doctor with experience in the treatment of chronic heart failure.

Treatment of stable chronic heart failure with Bisoprolol-Astrapharm begins according to the titration scheme below and may be adjusted depending on the individual body's reactions.

- 1.25 mg* bisoprolol fumarate once daily for 1 week; if well tolerated, increase to

- 3.75 mg** bisoprolol fumarate once daily for the next 1 week; if well tolerated, increase to

- 5 mg bisoprolol fumarate once daily for the next 4 weeks; if well tolerated, increase to

- 7.5 mg bisoprolol fumarate once daily for the next 4 weeks; if well tolerated, increase to

- 10 mg of bisoprolol fumarate once daily as maintenance therapy.

* At the beginning of therapy for chronic heart failure, it is recommended to use bisoprolol at a dosage of 2.5 mg.

** Use in appropriate dosage.

The maximum recommended dose of bisoprolol fumarate is 10 mg once daily.

During the titration phase, vital signs (blood pressure, heart rate) and symptoms of heart failure progression should be monitored. Symptoms may develop from the first day of treatment.

Treatment modification.

If the maximum recommended dose is not tolerated, a gradual dose reduction may be considered. If during or after the titration phase there is a gradual worsening of heart failure, hypotension or bradycardia, dose adjustment is recommended, which may require a temporary reduction in the bisoprolol dose or possibly discontinuation of treatment. After the patient's condition has stabilized, the possibility of reinitiating bisoprolol treatment should always be considered.

Treatment with the drug should not be stopped suddenly, especially in patients with ischemic heart disease, as this may lead to a deterioration in the patient's condition. If necessary, treatment with the drug is recommended to be discontinued slowly, gradually reducing the dose (for example, reducing the dose by half every week).

Treatment of stable chronic heart failure is usually long-term.

The course of treatment with bisoprolol is long and depends on the nature and severity of the disease.

Patients with hepatic and/or renal insufficiency.

Arterial hypertension; ischemic heart disease. For patients with mild to moderate hepatic or renal impairment, dose adjustment is usually not required. For patients with severe renal insufficiency (creatinine clearance less than 20 ml/min) and patients with severe hepatic insufficiency, the dose should not exceed a daily dose of 10 mg of Bisoprolol-Astrafarm. There are limited data on the use of bisoprolol in patients on dialysis. There is no need to change the dosage regimen.

Chronic heart failure. There are no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure concomitant with impaired liver or kidney function, therefore, increasing the dose should be done with caution.

Elderly patients do not require dose adjustment.

Children.

There are no clinical data on the efficacy and safety of bisoprolol in the treatment of children, therefore the drug is not recommended for use in pediatric practice.

Overdose.

Symptoms.

In case of overdose (for example, using a daily dose of 15 mg instead of 7.5 mg), cases of third-degree atrioventricular block, bradycardia and dizziness have been recorded. The most frequent signs of overdose with β-blockers are bradycardia, hypotension, acute heart failure, hypoglycemia and bronchospasm. To date, several cases of overdose (maximum dose - 2000 mg) of bisoprolol are known. Bradycardia or hypotension were noted. All patients recovered. 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. Therefore, treatment should be started with a gradual increase in dosage (see the section "Method of administration and dosage").

Treatment.

In case of overdose, you should immediately consult a doctor.

In case of overdose, discontinue treatment with the drug and provide supportive and symptomatic therapy. There is limited evidence that bisoprolol is poorly dialyzable. In case of suspected overdose, in accordance with the expected pharmacological effect and based on recommendations for other β-blockers, the following general measures should be considered.

For bradycardia: intravenous atropine. If there is no reaction, isoprenaline or another drug with a positive chronotropic effect should be administered with caution. In exceptional cases, transvenous administration of an artificial pacemaker may be necessary.

For hypotension: intravenous fluids and vasoconstrictors. Intravenous glucagon may be useful.

In case of atrioventricular block of the II and III degree: careful observation and infusion of isoprenaline or transvenous introduction of a pacemaker.

In case of exacerbation of chronic heart failure: intravenous administration of diuretics, inotropic drugs, vasodilators.

For bronchospasm: bronchodilators (e.g. isoprenaline), β2-adrenomimetics and/or aminophylline.

For hypoglycemia: intravenous glucose administration.

Cardiovascular system: bradycardia (in patients with chronic heart failure), signs of worsening heart failure (in patients with chronic heart failure), atrioventricular conduction disorders, bradycardia (in patients with arterial hypertension or ischemic heart disease), signs of worsening heart failure (in patients with arterial hypertension or ischemic heart disease), feeling of coldness or numbness of the extremities, arterial hypotension (in patients with arterial hypertension or ischemic heart disease), orthostatic hypotension (in patients with chronic heart failure).

Nervous system: dizziness*, headache*, syncope/fainting.

On the part of the organs of vision: decreased tear secretion (should be taken into account when wearing contact lenses), conjunctivitis.

On the part of the auditory organs: hearing impairment.

On the part of the respiratory system: bronchospasm in patients with bronchial asthma or a history of obstructive airway diseases, allergic rhinitis.

Gastrointestinal tract: nausea, vomiting, diarrhea, constipation.

Skin: hypersensitivity reactions, including itching, redness, rash; alopecia. When treated with β-blockers, worsening of the condition of patients with psoriasis in the form of a psoriatic rash may occur.

Musculoskeletal system: muscle weakness, cramps.

From the hepatobiliary system: hepatitis.

From the reproductive system: impaired potency.

Psychiatric: depression, sleep disorders, nightmares, hallucinations.

Laboratory indicators: increased triglyceride levels in the blood, increased activity of liver enzymes in blood plasma (AST, ALT).

General disorders: asthenia (in patients with chronic heart failure), fatigue *; infrequently - asthenia (in patients with arterial hypertension or ischemic heart disease).

* Applies only to patients with arterial hypertension or ischemic heart disease. These symptoms usually occur at the beginning of therapy, are mild and disappear within the first 1-2 weeks.

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

Expiration date.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 2, 3, 6 or 9 blisters in a box.

Vacation category.

According to the recipe.

Producer.

"Astrafarm" LLC.

Location of the manufacturer and address of its place of business.

Ukraine, 08132, Kyiv region, Kyiv-Svyatoshyn district, Vyshneve city, Kyivska st., 6.