Nebivolol-SZ - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 89.87 mg, pregelatinized starch (starch 1500) - 22.5 mg, croscarmellose sodium (impellosis) - 9.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) 4.5 mg, cellulose microcrystalline - 17.25 mg, silicon dioxide colloid (aerosil) - 0.38 mg, calcium stearate - 1.5 mg.

Description:Tablets are white or almost white, round, flat-cylindrical, with a facet and a cross-shaped risk.

Pharmacotherapeutic group:Beta1 - blockade selective blocker

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Cardioselective β₁-adrenergic blocker. Nebivolol has antihypertensive, anti-anginal and antiarrhythmic effects. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively blocks postsynaptic β₁-adrenoceptors, making them inaccessible to catecholamines, simulates the release of the endothelial vasodilating factor nitric oxide (NO).

Nebivolol is a racemate of two enantiomers: SRRR-nebivolol (D-nebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions:

- DNebivolol is a competitive and highly selective blocker β₁-adrenoceptors;

- L- Nebivolol has a mild vasodilating effect due to modulation of the release of the vasodilating factor (NO) from the vascular endothelium.

The hypotensive effect is also due to a decrease in the activity of the renin-angiotensin-aldosterone system (RAAS) (does not directly correlate with a change in renin activity in the blood plasma).

A stable hypotensive effect develops after 1-2 weeks of regular intake of the drug, and in some cases - after 4 weeks, a stable effect is observed after 1-2 months.

Reducing the need for myocardium in oxygen (decreasing heart rate (heart rate), reducing preload and afterload), nebivolol reduces the number and severity of angina attacks and increases the tolerance of exercise. Antiarrhythmic effect is due to suppression of pathological automatism of the heart (including in the pathological focus) and slowing of atrioventricular conduction.

Pharmacokinetics:

Suction. After oral administration, both enantiomers are rapidly absorbed.Eating does not affect absorption, therefore nebivolol can be taken regardless of food intake. Bioavailability of ingested nebivolol averages 12% in patients with "fast" metabolism (the effect of "primary transmission") and is almost complete - in patients with "slow" metabolism.

Distribution. In plasma, both enantiomers are predominantly associated with albumin. Binding to plasma proteins is for DNebivolol - 98.1%, for L- nebivolol - 97.9%.

Excretion. Metabolized nebivolol by alicyclic and aromatic hydrocylation and partial N-dealkylation. The resulting hydroxy- and amino derivatives are conjugated with glucuronic acid and are derived as O- and N-glucuronides, kidneys (38%), through the intestine (48%). T_1/2 in patients with a "fast" metabolism: hydrocimetabolites - 24 h, enantiomers nebivolol - 10 h; in patients with a "slow" metabolism: hydrocimetabolites - 48 hours, enantiomers of nebivolol - 30-50 hours. Removal of unchanged nebivolol through the kidneys is less than 0.5% of the dose taken internally.

Given the difference in metabolic rate, the dose of the drug should always be selected individually: patients with "slow" metabolism require a smaller dose.

Indications:

- Ahyperthermia;

- ischemic heart disease: prevention of angina pectoris attacks;

- chronic heart failure (as part of combination therapy).

Contraindications:

- Hypersensitivity to the active substance or to one of the components of the drug;

- acute heart failure;

- chronic heart failure in the stage of decompensation (requiring intravenous administration of drugs with inotropic effect);

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- syndrome of weakness of the sinus node, including sinoauric block;

- atrioventricular blockade of II and III degree (without artificial pacemaker);

- severe bradycardia (heart rate less than 50 beats per minute);

- cardiogenic shock;

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

- metabolic acidosis;

- severe violations of liver function;

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

- severe obliterating diseases of peripheral vessels ("intermittent" lameness, Raynaud's syndrome);

- myasthenia gravis;

- depression;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;

- age under 18 years (efficacy and safety in this age group not studied);

- simultaneous administration with floktaphenin, sultopride (see section "Interaction with other medicinal products")

Carefully:

- Renal failure;

- diabetes;

- hyperthyroidism;

- weighed allergic anamnesis; desensitizationtreatment, psoriasis;

- BA and COPD;

- atrioventricular blockade of the 1st degree;

- angina of Prinzmetal;

- age over 65 years.

Pregnancy and lactation:

In pregnancy, the drug Nebivolol appoint only for vital indications, when the benefit to the mother exceeds the possible risk to the fetus or newborn (due to possible development in the fetus and newborn bradycardia, arterial hypotension, hypoglycemia). If the drug treatment Nebivolol it is necessary, then it is necessary to observe the utero-placental blood flow and the development and growth of the fetus. Treatment should be discontinued 48 - 72 hours before delivery. In cases where this is not possible, it is necessary to establish strict observation of newborns within 48 to 72 hours after delivery.

Nebivolol is excreted in breast milk.If you need to take the drug Nebivolol during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Pills Nebivolol taken orally, once a day, preferably at the same time, regardless of food intake, squeezed a sufficient amount of liquid.

Average daily dose for treatment arterial hypertension and ischemic heart disease is 2.5 mg to 5 mg of the drug Nebivolol (1/2 tablet 5 mg - 1 tablet 5 mg).

Nebivolol can be used in monotherapy or in combination with other drugs that reduce blood pressure.

In patients with renal insufficiency, as well as in patients older than 65 years, the recommended initial dose is 1/2 tablet (1/2 tablet 5 mg) of the drug Nebivolol per day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tablets of 5 mg at one time).

Treatment of chronic heart failure should start with a slow increase in the dose until an individual optimal maintenance dose is reached. Selection of the dose at the beginning of treatment should be carried out according to the following scheme: while maintaining intervals of one to two weeks andfocusing on the tolerability of this dose by the patient: the initial dose is 1.25 mg (1/4 tablets 5 mg with a cross-like risk) once a day, can be increased first to 2.5-5 mg of the drug Nebivolol (1/2 tablet 5 mg - 1 tablet 5 mg), and then - up to 10 mg (2 tablets 5 mg) once a day.

The maximum daily dose is 10 mg (2 tablets 5 mg) once a day.

At the beginning of treatment and at each increase in the dose, the patient should be under the supervision of the doctor for at least 2 hours to ensure that the clinical condition remains stable (especially: Blood pressure, heart rate, conduction disorders, as well as symptoms of worsening of the course of chronic heart failure).

Nebivolol is not recommended in patients with severe renal and / or liver failure due to lack of experience.

Side effects:

Frequency of side effects: Often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), rarely (less than 0.01%), including individual reports.

Disturbances from the nervous system:

Often: headache, dizziness, increased fatigue, weakness, paresthesia;

Infrequently: depression, "nightmarish" dreams, confusion, decreased ability to concentrate, drowsiness, insomnia; Rarely: fainting, hallucinations.

Disorders from the gastrointestinal tract:

Often: dryness of the oral mucosa, nausea, constipation, diarrhea; Infrequently: dyspepsia, flatulence, vomiting.

Disorders from the cardiovascular system:

Infrequently: bradycardia, aggravation of the course of CHF, acute cardiac deficiency of atrioventricular conduction, atrioventricular blockade, marked decrease in blood pressure, orthostatic hypotension, cardiac arrhythmias, cardialgia, exacerbation of "intermittent" lameness, peripheral edema, Raynaud's syndrome.

Disturbances from the skin and subcutaneous tissues:

Infrequently: skin rash of erythematous nature, itching;

Rarely: aggravation of psoriasis, photodermatosis, increased sweating;

In some cases: angioedema.

Disturbances on the part of the organ of sight:

Infrequently: impaired vision.

Disturbances from the respiratory system:

Often: dyspnea;

Infrequently: bronchospasm, rhinitis.

Disorders from the reproductive system:

Infrequently: erectile disfunction.

Other violations: alopecia.

Overdose:

Symptoms: marked decrease in blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, atrioventricular (AV) blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest, hypoglycemia, convulsions.

Treatment: washing the stomach, taking activated charcoal. In the case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, with / injection of liquid and vasopressors. With bradycardia, it should be administered to / in 0.5 - 2 mg of atropine, in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be staged. With AV blockade (II-III st.), It is recommended to / in the administration of β-adrenergic stimulants, if they are ineffective, consider the question of setting an artificial pacemaker.When heart failure begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to administer dopamine , dobutamine or vasodilators.In bronchospasm, intravenous stimulants (β₂adrenoreceptors. With ventricular extrasystole - lidocaine (do not administer antiarrhythmic drugs IA class). When hypoglycemia - intravenous solution of dextrose (glucose), with convulsions - diazepam.

Interaction:

Pharmacodynamic interaction

At simultaneous application (β-adrenoblockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) the negative effect on myocardial contractility and AV conductivity. Contraindicated in / in the administration of verapamil against the background of nebivolol.

With the simultaneous use of nebivolol with antihypertensive drugs, nitroglycerin or BCCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin). The simultaneous use of baclofen and amifostine with antihypertensive drugs can cause a significant drop in blood pressure, so a dose adjustment of antihypertensive drugs is required.

With the simultaneous use of nebivolol with antihypertensive drugs of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of heart failure due to a decrease in sympathetic tone (decrease in heart rate and cardiac output, symptoms of vasodilation).In the case of a sudden withdrawal of these drugs, especially before the abolition of nebivolol, it is possible to develop a "ricochet" arterial hypertension.

With the simultaneous use of nebivolol with antiarrhythmic drugs of the first class and with amiodarone, an increase in the negative inotropic effect and prolongation of the excitation time at the atria are possible.

With the simultaneous use of nebivolol with cardiac glycosides, no increase in the effect on slowing AV conductivity.

Simultaneous use of nebivolol and preparations for general anesthesia can cause suppression of reflex tachycardia and increase the risk of developing arterial hypotension.

Clinically significant interactions of nebivolol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been established.

Simultaneous use of nebivolol with tricyclic antidepressants, barbiturates and phenothiazine derivatives can enhance the antihypertensive effect of nebivolol.

Contraindicated in the simultaneous use of nebivolol and floktaphenina, since there is a threat of a marked decrease in blood pressure or shock. Contraindicated in the simultaneous use of nebivolol and sultopride, as the risk of developing ventricular arrhythmia, especially as a pirouette, increases.

When applied simultaneously with nebivolol insulin and hypoglycemic agents for oral administration may be masked symptoms of hypoglycemia (tachycardia).

With the simultaneous use of sympathomimetic drugs suppress the activity of nebivolol.

Pharmacokinetic interaction

With simultaneous application of nebivolol with drugs that inhibit the reuptake of serotonin, or by other means involving isoenzyme Biotransformiroetsa CYP2D6, increases the concentration of nebivolol in the blood plasma, the metabolism of nebivolol slows down, which can lead to the risk of bradycardia.

When used simultaneously with digoxin, nebivolol no impact on the pharmacokinetic parameters of digoxin.

When applied simultaneously with nebivolol cimetidine, nebivolol plasma concentration increases.

Simultaneous use of nebivolol and ranitidine does not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increase slightly, but this has no clinical significance.

Simultaneous administration of nebivolol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

Clinically significant interactions of nebivolol and warfarin have not been established.

Special instructions:

Cancellation βadrenoblockers should be carried out gradually, within 10 days (up to 2 weeks in patients with ischemic heart disease). Control of blood pressure and heart rate at the beginning of the drug should be daily.

Older patients need control of kidney function (1 time in 4-5 months). With angina pectoris, the dose of the drug should provide a heart rate at rest within 55-60 bpm, with a load of no more than 110 beats per minute.

β- adrenoblockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 bpm. (see section "Contraindications").

When deciding on the use of the drug Nebivolol patients with psoriasis should carefully correlate the expected benefits of using the drug and the possible risk of exacerbation of the course of psoriasis. Patients using contact lenses should take into account that against the background of the use of β-adrenoblockers, the production of tear fluid can be reduced.

When conducting surgical interventions, an anesthesiologist should be warned that the patient is taking β-blockers.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, care should be taken when treating these patients, because the drug Nebivolol can mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic agents for ingestion and insulin. Control of the concentration of glucose in the blood plasma should be done 1 time in 4-5 months. (in patients with diabetes mellitus).

With hyperthyroidism, β-adrenoblockers can mask tachycardia.

β-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease, as bronchospasm may increase.

β-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions.

In smokers, the efficacy (β-adrenoblockers is lower compared to non-smokers.

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

During the period of drug treatment Nebivolol (in the event of side effects), care should be taken when driving vehicles and when engaging in potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 5 mg.

Packaging:

For 10 or 14 tablets in a contour mesh package.

For 30, 56 or 60 tablets in a can of polymer or a bottle of polymer. Each bank or bottle, 2, 3, 6 contour cell packs of 10 tablets or 1, 2, 3, 4 contour packs of 14 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002421

Date of registration:04.04.2014 / 02.03.2015

Expiration Date:04.04.2019

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp17.06.2018

Illustrated instructions

Instructions

Nebivolol-SZ (Nebivolol-sz)