Niperten, pills 10mg, 30pcs

Composition

for 1 tablet 2.5 mg / 5 mg / 10 mg

Core:

Active ingredient:

Bisoprolol Fumarate 2.50 mg / 5.00 mg/10.00 mg

Excipients: microcrystalline cellulose, sodium carboxymethyl starch, povidone-K 30, colloidal silicon dioxide, magnesium stearate

Film shell: hypromellose, macrogol 400, titanium dioxide (E 171) 0.42 mg, talc

Pharmacological action

beta-1-adrenoblocker selective

Clinical Pharmacology

Pharmacodynamics

Selective β_-1-adrenoblocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect. It has only a slight affinity for β2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for β2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect the resistance of the respiratory tract and metabolic processes in which β2-adrenergic receptors are involved.

The selective effect of the drug on β1-adrenergic receptors remains beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect. The maximum effect of the drug is achieved 3-4 hours after ingestion. Even when bisoprolol is used once a day, its therapeutic effect persists for 24 hours due to a 10-12-hour half-life (T_1/2) from blood plasma. As a rule, the maximum reduction in blood pressure (BP) is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system by blocking the beta_-1-adrenergic receptors of the heart.

When taken once orally in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces the heart rate (HR), reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially increased total peripheral vascular resistance decreases. A decrease in the activity of renin in blood plasma is considered as one of the components of the antihypertensive effect of beta-blockers.

Pharmacokinetics

Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to insignificant metabolism during the” primary passage ” through the liver (approximately 10%) is about 90% after oral use. Food intake does not affect bioavailability. Bisoprolol shows linear kinetics, and its plasma concentrations are proportional to the dose taken in the range from 5 to 20 mg. The maximum concentration in the blood plasma is reached in

2-3 hours.

Distribution

Bisoprolol is distributed fairly widely. The volume of distribution is 3.5 l / kg. Binding to plasma proteins reaches approximately 30%.

Metabolism

It is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and excreted by the kidneys. The main metabolites found in blood plasma and urine do not show pharmacological activity. Data obtained as a result of experiments with human liver microsomes in vitroshow that bisoprolol is primarily metabolized by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.

Deduction

The clearance of bisoprolol is determined by the balance between renal excretion unchanged (about 50%) and liver metabolism (about 50%) to metabolites that are also excreted by the kidneys. The total clearance is 15 l / h. T_1/2 – 10-12 hours.

Pharmacokinetics in different groups of patients

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concomitant hepatic or renal impairment.

Indications

* Arterial hypertension.

* Coronary heart disease: stable angina pectoris.

* Chronic heart failure.

Use during pregnancy and lactation

Pregnancy

During pregnancy, Niperten® should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and / or child.

As a rule, beta-blockers reduce blood flow in the placenta and can affect fetal development. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child, and in case of adverse events in relation to pregnancy and/or the fetus, alternative therapies with a proven safety profile of use during pregnancy should be taken. The newborn should be carefully examined after delivery. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur.

Breast-feeding period

There are no data on the excretion of bisoprolol in breast milk. Therefore, the use of Niperten® is not recommended for women during breastfeeding. If taking Niperten® during lactation is necessary, breast-feeding should be discontinued.

Contraindications

·  Hypersensitivity to bisoprolol or to any of the excipients (see the section “Composition”).

·  Acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy.

* Cardiogenic shock.

* Grade II and III atrioventricular (AV) block, without pacemaker.

* Sinus node weakness syndrome.

* Sinoatrial blockade.

·  Severe bradycardia (heart rate less than 60 beats / min).

·  Severe arterial hypotension (systolic blood pressure less than 100 mm Hg).

·  Severe forms of bronchial asthma.

* Severe peripheral arterial circulatory disorders or Raynaud’s syndrome.

* Pheochromocytoma (without simultaneous use of alpha-blockers).

* Metabolic acidosis.

·  Under 18 years of age (insufficient data on efficacy and safety in this age group).

Side effects

The frequency of adverse reactions listed below was determined according to the following criteria recommended by the World Health Organization: very common (≥ 1/10); common (≥ 1/100 to < 1/10); infrequent (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (

Nervous system disorders:

common: dizziness*, headache*;

rare: loss of consciousness.

Mental disorders:

infrequently: depression, insomnia;

rarely: hallucinations, nightmares.

Visual disturbances:

rarely: reduced tear production (should be considered when wearing contact lenses);

very rarely: conjunctivitis.

Hearing disorders and labyrinth disorders:

rare: hearing loss.

Disorders of the heart and blood vessels:

very common: bradycardia (in patients with heart failure);

often: the worsening symptoms of CHF currents (in patients with CHF), a sensation of cold, or numbness in the extremities, marked reduction in blood pressure, particularly in patients with chronic heart failure;

infrequent: violation of AV conduction, bradycardia (in patients with hypertension or angina pectoris), worsening symptoms of CHF currents (in patients with hypertension or angina pectoris), orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders:

infrequently: bronchospasm in patients with a history of bronchial asthma or airway obstruction;

rarely: allergic rhinitis.

Disorders of the gastrointestinal tract:

often: nausea, vomiting, diarrhea, constipation.

Liver and biliary tract disorders:

rare: hepatitis.

Musculoskeletal and connective tissue disorders:

infrequently: muscle weakness, muscle cramps.

Skin and subcutaneous tissue disorders:

rare: hypersensitivity reactions, such as pruritus, skin rash, hyperemia of the skin;

very rare: alopecia.

beta-blockers may exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

Genital and breast disorders:

rare: violation of potency.

General disorders and disorders at the injection site:

often: asthenia (in patients with CHF), increased fatigue*;

infrequently: asthenia (in patients with arterial hypertension or angina pectoris).

Laboratory and instrumental data:

rarely: increased concentration of triglycerides and activity of “hepatic” transaminases (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)) in blood plasma.

* In patients with arterial hypertension or angina pectoris, these symptoms appear especially often at the beginning of the course of treatment. Usually, these symptoms are mild and usually disappear within 1-2 weeks after the start of treatment.

Interaction

The efficacy and tolerability of bisoprolol may be affected by concomitant use of other medications. Such an interaction can also occur in cases where two drugs are taken after a short period of time.

It is necessary to inform the doctor about taking other medications, even if they are taken without a doctor’s prescription (i. e. over-the-counter medications).

Not recommended combinations

Treatment of chronic heart failure

Class I antiarrhythmic agents (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility.

All indications for the use of Niperten®

Slow calcium channel blockers (BCCs) such as verapamil and, to a lesser extent, diltiazem, when used concomitantly with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous use of verapamil to patients taking beta-blockers may lead to severe hypotension and AV block. Antihypertensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before beta-blockers are discontinued, may increase the risk of developing “rebound” hypertension.

Combinations that require extreme caution

Treatment of arterial hypertension and angina pectoris

Class I antiarrhythmic agents (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility.

All indications for the use of Niperten®

BMCC, dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine) when used simultaneously with bisoprolol may increase the risk of hypotension. In patients with CHF, the risk of subsequent deterioration of the contractile function of the heart cannot be excluded.

Class III antiarrhythmic agents (such as amiodarone) may increase the violation of AV conduction.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may increase the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

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

The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia, such as tachycardia, may be masked or suppressed. Such interactions are more likely to occur with non-selective beta-blockers.

General anaesthetic agents may increase the risk of cardiodepressive effects, leading to hypotension (see section “Special instructions”).

Cardiac glycosides, when used concomitantly with bisoprolol, can lead to an increase in pulse conduction time, and thus to the development of bradycardia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of bisoprolol.

Concomitant use of Niperten® with beta-adrenomimetics (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs. The use of bisoprolol with adrenomimetics that affect alpha-and beta-adrenergic receptors (for example, norepinephrine, epinephrine) may increase 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 to occur with non-selective beta-blockers.

Antihypertensive agents, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the antihypertensive effect of bisoprolol.

Mefloquine, when co-administered with bisoprolol, may increase the risk of developing bradycardia.

Monoamine oxidase (MAO)inhibitors (with the exception of MAO B inhibitors) may enhance the antihypertensive effect of beta-blockers. Simultaneous use can also lead to the development of a hypertensive crisis.

How to take, course of use and dosage

Inside,1 time a day with a small amount of liquid, in the morning, regardless of the time of meal.

Tablets should not be chewed or ground into powder.

Arterial hypertension and stable angina pectoris

In all cases, the mode of use and dose is selected by the doctor for each patient individually, in particular, taking into account the patient’s heart rate and condition.

Usually, the initial dose is 5 mg of Niperten® once a day. If necessary, the dose can be increased to 10 mg once a day.

In the treatment of arterial hypertension and stable angina, the maximum recommended dose is 20 mg of Niperten® once a day.

Chronic heart failure

The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. Initiation of CHF treatment with Niperten® requires a special titration phase and regular medical monitoring.

A prerequisite for treatment with Niperten® is stable chronic heart failure without signs of exacerbation.

Treatment of CHF with Niperten® begins according to the following titration schedule. However, individual adjustment may be required depending on how well the patient tolerates the prescribed dose, i. e. the dose can only be increased if the previous dose was well tolerated.

The recommended starting dose is 1.25 mg (1/2 tablet of 2.5 mg) once a day. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg,3.75 mg,5 mg,7.5 mg and 10 mg once a day. Each subsequent dose increase should be carried out at least 2 weeks later.

If an increase in the dose of the drug is poorly tolerated by the patient, it is possible to reduce the dose.

The maximum recommended dose for the treatment of CHF is 10 mg of Niperten® once a day.

During titration, regular monitoring of blood pressure, heart rate, and the severity of CHF symptoms is recommended. Worsening of the symptoms of CHF is possible from the first day of use of the drug.

If the patient does not tolerate the maximum recommended dose of Niperten®, consideration should be given to gradually reducing the dose.

During or after the titration phase, there may be a temporary deterioration in the course of CHF, hypotension, or bradycardia. In this case, it is recommended, first of all, to adjust the doses of concomitant therapy. It may also be necessary to temporarily reduce the dose of Niperten® or cancel it.

After the patient’s condition stabilizes, the dose should be re-titrated or the treatment should be continued.

Duration of treatment for all indications for the use of Niperten®

Treatment with Niperten® is usually long-term therapy.

Special patient groups

Impaired kidney or liver function

In cases of mild or moderate hepatic or renal impairment, no dose adjustment is usually required.

In patients with severe renal impairment (creatinine clearance 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 done with extreme caution.

Elderly patients

No dose adjustment is required.

Children

Since there is insufficient data on the use of Niperten® in children, it is not recommended to use the drug in children under 18 years of age.

Currently, there are insufficient data on the use of Niperten® in patients with CHF in combination with type 1 diabetes mellitus, severe renal and/or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic disorders. Also, until now, not enough data have been obtained on patients with CHF with myocardial infarction in the last 3 months.

Overdose

Symptoms

The most common symptoms of overdose are AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure, and hypoglycemia.

Sensitivity to a single high dose of bisoprolol varies greatly among individual patients, and it is likely that patients with CHF are highly sensitive.

Treatment

If an overdose occurs, first of all, it is necessary to stop taking the drug and start supportive symptomatic therapy.

For severe bradycardia: intravenous use of atropine. If the effect is insufficient, you can use caution to introduce a drug that has a positive chronotropic effect.Sometimes it may be necessary to temporarily install an artificial pacemaker.

With a marked decrease in blood pressure: intravenous use of plasma-substituting solutions and vasopressors.

For AV block: patients should be constantly monitored and treated with alpha-and beta-adrenomimetics, such as epinephrine (epinephrine). If necessary, an artificial pacemaker can be installed.

In case of exacerbation of CHF: intravenous use of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

In case of bronchospasm: use of bronchodilators, including beta_-2-adrenomimetics and / or aminophylline.

Hypoglycemia: intravenous use of dextrose (glucose).

Description

2.5 mg tablets: Oval, biconvex tablets, white film-coated tablets with a risk on one side.

View at the break: a rough mass of white or almost white color with a white film shell.

5 mg and 10 mg tablets: Round, biconvex tablets, white film-coated tablets with a risk on one side.

View at the break: a rough mass of white or almost white color with a white film shell.

Special instructions

Pthe Providence desensitizing therapies, Prinzmetal’s angina, hyperthyroidism, diabetes mellitus type 1 and diabetes mellitus, with significant fluctuations in the concentration of glucose in the blood, AV blockade of I degree, severe renal insufficiency (creatinine clearance (CC) of less than 20 ml/min), severe liver function abnormalities, psoriasis, restrictive cardiomyopathy, congenital heart defect or heart valve with severe hemodynamic disorders, CHF and myocardial infarction within the last 3 months, severe forms of chronic obstructive pulmonary disease, a strict diet

Since there is insufficient data on the use of Niperten® in children, it is not recommended to use the drug in children under 18 years of age.

Impaired kidney or liver function

In cases of mild or moderate hepatic or renal impairment, no dose adjustment is usually required.

In patients with severe renal impairment (creatinine clearance 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 done with extreme caution.

Elderly patients

No dose adjustment is required.

 

Do not abruptly discontinue treatment with Niperten® and do not change the recommended dose without first consulting your doctor, as this may lead to temporary deterioration of heart activity. Treatment should not be interrupted abruptly, especially in patients with CHD. If discontinuation of treatment is necessary, the dose should be reduced gradually.

When clonidine is used concomitantly, its use may be discontinued only a few days after discontinuation of Niperten®.

At the initial stages of treatment with Niperten®, patients need constant monitoring.

Monitoring the condition of patients taking Niperten® should include measuring heart rate and blood pressure (at the beginning of treatment – daily, then – once every 3-4 months), performing an electrocardiogram, determining the concentration of glucose in the blood in patients with diabetes mellitus (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months).

The patient should be trained in the method of calculating heart rate and instructed to consult a doctor if the heart rate is less than 60 beats/min.

Niperten® should be used with caution in the following cases::

· severe forms of COPD and mild forms of bronchial asthma;

· diabetes mellitus with significant fluctuations in the concentration of glucose in the blood plasma: symptoms expressed lower concentrations of glucose (hypoglycemia), such as tachycardia, palpitations or sweating may be masked;

· a strict diet;

· conducting desensitizing therapies;

· AV blockade of I degree;

· Prinzmetal’s angina;

· impaired peripheral arterial circulation of mild and moderate degree (at the beginning of therapy may be increased symptoms);

· psoriasis (including in the anamnesis).

If elderly patients are found to have increasing bradycardia (heart rate less than 60 beats/min), a marked decrease in blood pressure (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver and/or kidney function disorders, it is necessary to reduce the dose of the drug or discontinue treatment.

It is recommended to stop therapy if you develop depression caused by taking beta-blockers.

Respiratory system

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

In patients with bronchial asthma or COPD, concomitant use of bronchodilators is indicated. Patients with bronchial asthma may have increased airway resistance, which requires a higher dose of beta_-2-adrenomimetics.

In “smokers”, the effectiveness of beta-blockers is lower. In patients with COPD, bisoprolol, which is prescribed in combination therapy for the treatment of heart failure, should be started with the lowest possible dose, and patients should be carefully monitored for new symptoms (for example, shortness of breath, exercise intolerance, cough).

Allergic reactions

beta-blockers, including Niperten®, may increase sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of their adrenergic compensatory regulation under the action of beta-blockers. Epinephrine (epinephrine) therapy does not always produce the expected therapeutic effect.

General anesthesia

When performing general anesthesia, the risk of beta-adrenergic blockade should be taken into account. If it is necessary to stop therapy with Niperten® before surgery, this should be done gradually, and completed48 hours before general anesthesia. You should inform your anaesthetist that you are taking Niperten®.

Pheochromocytoma

In patients with an adrenal tumor (pheochromocytoma), Niperten® can only be used against the background of simultaneous use of alpha-blockers.

Hyperthyroidism

Symptoms of hyperthyroidism (hyperthyroidism) may be masked when treated with Niperten®.

Patients who use contact lenses should take into account that during treatment, there may be a decrease in the production of tear fluid.

The drug Niperten® does not affect the ability to drive vehicles according to the results of the study in patients with CHD. However, due to individual reactions, the ability to drive vehicles or work with technically complex mechanisms may be impaired. This should be paid special attention at the beginning of treatment, after changing the dose, as well as when drinking alcohol at the same time.

Form of production

Film-coated tablets,2.5 mg,5 mg,10 mg.

10 tablets each in a contour cell pack made of PVC film and aluminum foil.

2,3,5 or 10 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Bisoprolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Arrhythmia, Heart Failure, Hypertension