Niperten - instructions for use, dose, side effects, contraindications

Core: dActive substance: bisoprolol fumarate 2.50 mg; Excipients: cellulose microcrystalline 95.50 mg, carboxymethyl starch sodium 15.00 mg, povidone 2.00 mg, silicon dioxide colloid 1.0 mg, magnesium stearate 1.00 mg;

Film Sheath: hypomellose 1.33 mg, macrogol 400 0.42 mg, titanium dioxide (E 171) 0.42 mg, talc 0.83 mg.

For 1 tablet of 5 mg:

Core: dActive substance: bisoprolol fumarate 5.00 mg; Excipients: cellulose microcrystalline 93.00 mg, carboxymethyl starch sodium 15.00 mg, povidone 2.00 mg, silicon dioxide colloid 1.0 mg, magnesium stearate 1.00 mg;

Film Sheath: hypromellose 1.33 mg, macrogol 400 0.42 mg, titanium dioxide (E 171) 0.42 mg, talc 0.83 mg.

For 1 tablet of 10 mg:

Core: dactive substance: bisoprolol fumarate 10.00 mg; atExcipients: microcrystalline cellulose 186.00 mg, sodium carboxymethyl starch 30.00 mg, povidone 4.00 mg, silicon dioxide colloid 2.0 mg, magnesium stearate 2.00 mg;

Film Sheath: hypromellose 2.66 mg, macrogol 400 0.84 mg, titanium dioxide (E 171) 0.84 mg, talc 1.66 mg

Description:

Tablets 2.5 mg: Oval, biconvex tablets, covered with a film shell of white color, with a risk on one side. View of the fracture: a rough mass of white or almost white with a film shell of white color.

Tablets 5 mg: Round, biconvex tablets, covered with a film shell of white color, with a risk on one side. View of the fracture: a rough mass of white or almost white with a film shell of white color.

Tablets 10 mg: Round, biconvex tablets, covered with a film shell of white color, with a risk on one side. View of the fracture: a rough mass of white or almost white with a film shell of white color.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.B.07 Bisoprolol

Pharmacodynamics:

Selective β₁- adrenoblocker, without its own sympathomimetic activity, does not possess membrane-stabilizing action. It has only a slight affinity for β₂-adrenoreceptors of smooth muscles of bronchi and vessels, and also to β₂adrenoreceptors involved in the regulation of metabolism. Consequently, bisoprolol in general, does not affect the resistance of the respiratory tract and the metabolic processes in which β₂-adrenoceptors.

Selective action of the drug on β₁-adrenoceptors persists 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 with bisoprolol applied once a day, its therapeutic effect persists for 24 hours due to the 10-12-hour half-life (T_1/2) from the 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 β₁-adrenoceptors of the heart.

With a single oral intake in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF) bisoprolol it reduces the heart rate (heart rate), reduces the shock volume of the heart and, as a consequence, reduces the ejection fraction and myocardial oxygen demand. With prolonged therapy, initially increased total peripheral vascular resistance is reduced. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of β-adrenoblockers.

Pharmacokinetics:

Suction

Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal fact.Its bioavailability due to insignificant metabolization during "primary passage" through the liver (about 10%) is about 90% after ingestion. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its concentrations in the blood plasma are proportional to the dose taken in the range of 5 to 20 mg. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution

Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l / kg. The connection with plasma proteins is approximately 30%.

Metabolism

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. The data obtained as a result of experiments with microhomes of the human liver under conditions in vitro, show that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only a minor role.

Excretion

Bisoprolol clearance is determined by the balance between excretion by the kidneys in an unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites that are also excreted by the kidneys.The total ground clearance is 15 liters per hour. T_1/2- 10-12 hours.

Pharmacokinetics in different patient groups

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and simultaneous impairment of liver or kidney function.

Indications:

- Arterial hypertension;

- ischemic heart disease: stable angina;

- chronic heart failure.

Contraindications:

- Hypersensitivity to bisoprolol or any of the excipients of the drug;

- acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- atrioventricular (AV) blockade of II and III degree, without an electrocardiostimulator;

- syndrome of weakness of the sinus node;

- sinoatrial blockade;

- severe bradycardia (heart rate less than 60 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

- severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD);

- severe peripheral arterial circulation or Raynaud's syndrome;

- pheochromocytoma (without simultaneous use of alpha-blockers);

- metabolic acidosis;

- age under 18 years (insufficient data on the effectiveness and safety of this age group).

Carefully:

Carrying out desensitizing therapy, angina pectoris Prinzmetal, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, AV blockade of I degree, severe renal failure (creatinine clearance less than 20 ml / min), severe liver dysfunction, psoriasis, restrictive cardiomyopathy, congenital heart disease or heart valve disease with severe hemodynamic disorders, CHF with myocardial infarction during the last 3 -th months, strict diet.

Pregnancy and lactation:

Pregnancy

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

As a rule, β-adrenoblockers reduce blood flow in the placenta and can affect fetal development. Blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be monitored and, in the event of undesirable pregnancy and / or fetal events, alternative therapies with a proven safety profile during pregnancy.You should carefully examine the newborn after delivery. In the first three days of life, bradycardia and hypoglycemia may occur.

Breastfeeding period

There is no data on the isolation of bisoprolol in breast milk. Therefore, taking Niperten ® is not recommended for women during breastfeeding. If Niperten® is needed during lactation, breastfeeding should be discontinued.

Dosing and Administration:

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

Tablets should not be chewed or ground into a powder.

Arterial hypertension and stable angina

In all cases, the regimen and dosage are selected by the doctor for each patient individually, in particular, taking into account the heart rate and the patient's condition.

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

In the treatment of 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 receptor antagonists II (in case of intolerance to ACE inhibitors), β-adrenoblockers, diuretics and, optionally, cardiac glycosides. The initiation of treatment with CHF with Niperten® requires a special phase of titration and regular medical supervision.

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

Treatment of CHF with Niperten® begins in accordance with the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e., the dose can be increased only if the previous dose is well tolerated. The recommended initial dose is 1.25 mg (1/2 tablets of 2.5 mg) once a day. Depending on the individual tolerability, the dose should be gradually increased to 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg once daily. Each subsequent increase in the dose should be carried out at least 2 weeks later.

If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible.

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 severity of CHF symptoms is recommended. The aggravation of the symptoms of CHF is possible from the first day of the drug.

If the patient does not tolerate the maximum recommended dose of NIPERTEN®, a gradual dose reduction should be considered.

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

After stabilization of the patient's condition, a repeated titration of the dose should be performed, or the treatment should be continued.

The duration of treatment with all indications for the use of Niperten®

Treatment with drug Niperten® is usually a long-term therapy.

Impaired renal or hepatic function

If the liver or kidney function is mild or moderate, usually no dose adjustment is required.

With severe renal dysfunction (KC 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.

Elderly patients

Correction of the dose is not 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 is insufficient data on the use of Niperten® in patients with CHF in combination with type 1 diabetes, severe renal and / or hepatic impairment, restrictive cardiomyopathy, congenital heart disease, or heart valve disease with severe hemodynamic impairment. Also, until now, there has been insufficient data on patients with CHF with myocardial infarction during the last 3 months.

Side effects:

The incidence of adverse reactions listed below was determined according to the following criteria recommended by the World Health Organization: very often (≥ 1/10); often (≥ 1/100 to <1/10); infrequently (≥ 1/1000 to <1/100); rarely (≥ 1/10000 to <1/1000); very rarely (<1/10000).

Impaired nervous system:

often: dizziness *, headache *;

rarely: loss of consciousness.

Disorders of the psyche:

infrequently: depression, insomnia;

rarely: hallucinations, nightmares.

Disorders from the side of the organ of vision:

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

very rarely: conjunctivitis.

Hearing disorders and labyrinthine disturbances:

rarely: hearing loss.

Violations from the heart and blood vessels:

very often: bradycardia (in patients with CHF);

often: aggravation of symptoms of CHF flow (in patients with CHF), sensation of cold or numbness in the extremities, marked decrease in blood pressure, especially in patients with CHF;

infrequently: violation AV conduction, bradycardia (in patients with hypertension or angina pectoris), aggravation of symptoms of CHF flow (in patients with arterial hypertension or angina pectoris), orthostatic hypotension.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently: bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis;

rarely: allergic rhinitis.

Disorders from the gastrointestinal tract:

often: nausea, vomiting, diarrhea, constipation.

Disorders from the liver and bile ducts:

rarely: hepatitis.

Disturbances from the musculoskeletal and connective tissue:

infrequently: muscle weakness, muscle cramps.

Disturbances from the skin and subcutaneous tissues:

rarely: hypersensitivity reactions, such as itchy skin, skin rash, hyperemia of the skin;

very rarely: alopecia.

β-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

Violations of the genitals and breast:

rarely: a violation of potency.

General disorders and disorders at the site of administration:

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

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

Laboratory and instrumental data:

rarely: an increase in the concentration of triglycerides and the activity of "hepatic" transaminases (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)) in the blood plasma.

* In patients with hypertension or angina pectoris, especially these symptoms appear at the beginning of the course of treatment. Usually, these phenomena are of an easy nature and usually pass within 1-2 weeks after the start of treatment.

Overdose:

Symptoms

The most common symptoms of an overdose are: AV blockade, pronounced bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

The sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients and, probably, patients with CHF are highly sensitive.

Treatment

When an overdose occurs, first of all, it is necessary to stop taking the drug and begin supporting symptomatic therapy.

With a pronounced bradycardia: intravenous administration of atropine. If the effect is insufficient, with caution, you can enter a drug that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With a pronounced decrease in blood pressure: intravenous injection of plasma-substituting solutions and vasopressor preparations.

When AV blockade: patients should be under constant observation and receive treatment with α- and β-adrenomimetics, such as epinephrine (adrenalin). If necessary - staging an artificial pacemaker.

With exacerbation of CHF flow: intravenous injection of diuretics, drugs with a positive inotropic effect,as well as vasodilators.

With bronchospasm: the use of bronchodilators, including β₂adrenomimetics and / or aminophylline.

When hypoglycemia: intravenous dextrose (glucose).

Interaction:

The effectiveness and tolerability of bisoprolol may be influenced by simultaneous intake of other drugs. This interaction can also occur when two drugs are taken in a short time. It is necessary to inform the doctor about taking other medications, even if they are taken without the doctor's prescription (that is, over-the-counter medications).

Unrecommended combinations

Treatment of chronic heart failure

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the myocardium.

All indications for the use of Niperten®

The blockers of "slow" calcium channels (BCCC) such as verapamil and to a lesser extent diltiazem with simultaneous application with bisoprolol may lead to a decrease in myocardial contractility and disruption AV conductivity.In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade. Hypotensive 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 the central sympathetic tone. Sharp cancellation, especially before cancellation βadrenoblockers, may increase the risk of developing "ricochet" arterial hypertension.

Combinations requiring special care

Treatment of arterial hypertension and angina

All indications for the use of Niperten®

BCCC, dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine) with simultaneous application with bisoprolol may increase the risk of developing arterial hypotension.In patients with heart failure, the risk of subsequent deterioration of the contractile function of the heart can not be ruled out.

Antiarrhythmic drugs of the III class (for example, amiodarone) can increase the violation AV conductivity.

The action of β-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

Parasympatomimetics with simultaneous use with bisoprolol may increase the disruption AV conductivity and increase the risk of developing a bradycardia.

The hypoglycemic effect of insulin or hypoglycemic agents for oral ingestion may be enhanced. Symptoms of hypoglycemia, in particular tachycardia, can be masked or suppressed. Similar interactions are more likely when using non-selective β-blockers.

Means for general anesthesia may increase the risk of cardiodepressive action, leading to hypotension (see section "Special instructions").

Cardiac glycosides with simultaneous application with bisoprolol may lead to to an increase in the timing of the impulse and, thus, the development of bradycardia.

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

The simultaneous use of Niperten® with β-adrenomimetics (for example, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs. The use of bisoprolol with adrenomimetics that affect α- and β-adrenergic receptors (for example, norepinephrine, epinephrine), can enhance the vasoconstrictor effects of these agents that occur with the participation of α-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective β-blockers.

Hypotensive drugs, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can enhance the antihypertensive effect of bisoprolol.

Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.

Inhibitors of monoamine oxidase (MAO) (with the exception of MAO B inhibitors) can enhance the antihypertensive effect of β-blockers. Simultaneous application can also lead to the development of hypertensive crisis.

Special instructions:

Do not interrupt treatment with Niperten ® drastically and do not change the recommended dose without first consulting a doctor, as this can lead to a temporary worsening of the heart. Treatment should not be interrupted suddenly, especially in patients with ischemic heart disease. If cessation of treatment is necessary, then the dose should be reduced gradually.

With the simultaneous use of clonidine, its administration can be stopped only a few days after the abolition of Niperten®.

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

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

It is necessary to teach the patient how to calculate the heart rate and instruct him about the necessity of consulting a doctor at a heart rate of less than 60 beats per minute.

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

- diabetes mellitus with significant fluctuations in plasma glucose concentration: symptoms of marked decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations or increased sweating may be masked;

- strict diet;

- conducting desensitizing therapy;

- AV blockade of the 1st degree;

- angina of Prinzmetal;

- violations of peripheral arterial blood flow of mild and moderate degree (at the beginning of therapy there may be an increase in symptoms);

- psoriasis (including in the anamnesis).

If older bradycardia is detected in elderly patients (heart rate less than 60 beats / min), pronounced BP reduction (systolic blood pressure below 100 mmHg) AV blockade, bronchospasm, ventricular arrhythmias, severe liver and / or kidney dysfunction, it is necessary to reduce the dose of the drug or stop treatment. It is recommended to stop therapy with the development of depression caused by the admission of β-blockers.

Respiratory system

Before the start of therapy, it is recommended to perform an external respiration function in patients with a history of bronchopulmonary anamnesis.

With bronchial asthma or COPD, simultaneous use of bronchodilating agents is indicated. In patients with bronchial asthma, an increase in airway resistance may be required, which requires a higher dose of β₂-adrenomimetics. In "smokers" the effectiveness of β-blockers is lower.

Allergic reactions

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

General anesthesia

When conducting general anesthesia, the risk of blockade of β-adrenergic receptors should be considered. If it is necessary to discontinue therapy with Niperten® before surgery, it should be done gradually and completed 48 hours before the general anesthesia. An anesthesiologist should be warned that you are taking Niperten®.

Pheochromocytoma

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

Hyperthyroidism

When treating with Niperten®, the symptoms of hyperthyroidism (hyperthyroidism) may be masked.

Patients who use contact lenses should take into account that a reduction in tear fluid production is possible against the background of treatment.

Effect on the ability to drive transp. cf. and fur:

The drug Niperten® does not affect the ability to drive vehicles according to the results of the study in patients with IHD. However, due to individual reactions, the ability to drive vehicles or work with technically complex machinery can be disrupted. This should be paid special attention at the beginning of treatment, after changing the dose, as well as with the simultaneous use of alcohol.

Form release / dosage:

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

Packaging:

For 10 tablets in a planar cell pack of PVC film and aluminum foil.

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

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008962/09

Date of registration:06.11.2009

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp26.11.2015

Illustrated instructions

Instructions

Niperten® (Niperten®)