Nebivolol-SZ pills 5mg 56pcs

Composition

1 tablet contains:

Active ingredient:

nebivolol hydrochloride in terms of nebivolol – 5.0 mg;

excipients:

lactose monohydrate (milk sugar) – 89,87 mg,

pregelatinization starch (starch 1500) – 22,5 mg,

KROS-carmellose sodium (Primerose) – 9.0 mg,

povidone (polyvinylpyrrolidone middle) – 4,5 mg,

microcrystalline cellulose – 17,25 mg,

silicon dioxide colloid (Aerosil) – 0,38 mg,

calcium stearate – 1.5 mg.

Pharmacological properties

Pharmacotherapeutic group of the medicinal product:

beta-1-adrenoblocker selective

ATX code: [C 07 AB 12]

Pharmacological properties

Pharmacodynamics

Cardioselective β1-adrenoblocker. Nebivolol has antihypertensive, antianginal and antiarrhythmic effects. Reduces high blood pressure (BP) at rest, during physical exertion and stress. Competitively and selectively blocks postsynaptic β1-adrenergic receptors, making them inaccessible to catecholamines, simulates the release of endothelial vasodilating factor nitric oxide (NO).

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

– D-nebivolol is a competitive and highly selective blocker of β1-adrenergic receptors;

– L-nebivolol has a mild vasodilating effect by modulating the release of 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) (it does not directly correlate with changes in the activity of renin in blood plasma).

Stable hypotensive effect develops after 1-2 weeks of regular use of the drug, and in some cases – after 4 weeks, stable effect is noted after 1-2 months.

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

Pharmacokinetics

Suction. After oral use, both enantiomers are rapidly absorbed. Food intake does not affect absorption, so nebivolol can be taken regardless of food intake. The oral bioavailability of nebivolol is on average 12% in patients with a “fast” metabolism (the “primary passage” effect) and is almost complete in patients with a” slow ” metabolism.

Distribution. In blood plasma, both enantiomers are predominantly bound to albumin. Binding to plasma proteins is 98.1% for D-nebivolol and 97.9% for L-nebivolol.

Output. Nebivolol is metabolized by alicyclic and aromatic hydroskylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and are excreted as O-and N-glucuronides by the kidneys (38%) and through the intestines (48%). T 1/2 in patients with “fast” metabolism: hydroskimetabolites – 24 hours, nebivolol enantiomers – 10 hours; in patients with “slow” metabolism: hydroskimetabolites – 48 hours, nebivolol enantiomers – 30 – 50 hours. Excretion of unchanged nebivolol through the kidneys is less than 0.5% of the dose of the drug taken orally.

Taking into account the differences in the metabolic rate, the dose of the drug should always be selected individually: patients with a” slow ” metabolism need a smaller dose.

Indications

-arterial hypertension;

– coronary heart disease: prevention of angina attacks of tension;

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

Contraindications

– hypersensitivity to the Active ingredient or to any component of the drug;

acute heart failure;

– chronic heart failure in the stage of decompensation (requiring intravenous drugs with inotropic action);

– severe hypotension (systolic BP less than 90 mm Hg. St. )

– the syndrome of weakness of the sinus node, including sinoauricular blockade;

– atrioventricular block II and III degree (without an artificial pacemaker);

– severe bradycardia (heart rate less than 50 beats/min);

– cardiogenic shock;

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

metabolic acidosis;

severe disturbances of liver function;

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

– severe occlusive peripheral vascular disease (“alternating” claudication Raynaud’s syndrome);

– myasthenia gravis;

– depression;

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

– age up to 18 years (efficacy and safety in this age group have not been studied);

– simultaneous reception with floctafenine, sultopride (see section “Interaction with other medicinal products”).

With caution

– renal failure;

– diabetes mellitus;

– hyperthyroidism;

– burdened allergic history; desensitizing therapy, psoriasis;

– asthma and COPD;

– atrioventricular block I degree;

– Prinzmetal angina pectoris;

– age over 65 years.

Side effects

Frequency of side effects:  very 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%), very rarely (less than 0.01%), including individual messages.

Nervous system disorders:

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

Infrequently:  depression, “nightmarish” dreams, confusion, decreased ability to concentrate, drowsiness, insomnia;

Very rare:  fainting, hallucinations.

Disorders of the gastrointestinal tract:

Often:  dryness of the oral mucosa, nausea, constipation, diarrhea;

Infrequently:  dyspepsia, flatulence, vomiting.

Disorders of the cardiovascular system:

Infrequently:  bradycardia, worsening of CHF, acute heart failure, slowing of atrioventricular conduction, atrioventricular block, marked decrease in blood pressure, orthostatic hypotension, cardiac arrhythmias, cardialgia, exacerbation of “intermittent” claudication, peripheral edema, Raynaud’s syndrome.

Skin and subcutaneous tissue disorders:

Infrequently:  erythematous skin rash, pruritus;

Very rare:  aggravation of psoriasis, photodermatosis, increased sweating;

In some cases:  angioedema.

Visual disturbances:

Infrequently:  visual impairment.

Respiratory system disorders:

Often:  shortness of breath;

Infrequently:  bronchospasm, rhinitis.

Reproductive system disorders:

Infrequently:  erectile dysfunction.

Other violations:  allopecia.

Interaction

Pharmacodynamic interaction

Concomitant use of beta-blockers with “slow” calcium channel blockers (BMCC) (verapamil and diltiazem) increases the negative effect on myocardial contractility and AV conduction. Intravenous use of verapamil with nebivolol is contraindicated.

When nebivolol is co-administered with antihypertensive agents, nitroglycerin or BMCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin).

Concomitant use of baclofen and amifostine with antihypertensive drugs can cause a significant drop in blood pressure, so dose adjustment of antihypertensive drugs is required.

Concomitant 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 (decreased heart rate and cardiac output, symptoms of vasodilation). If these drugs are abruptly discontinued, especially before nebivolol is discontinued, “rebound” hypertension may develop.

Concomitant use of nebivolol with Class I antiarrhythmic drugs and amiodarone may increase the negative inotropic effect and prolong the time of atrial excitation.

Concomitant use of nebivolol with cardiac glycosides did not reveal an increased effect on the slowing of AV conduction.

Concomitant use of nebivolol and general anaesthetic agents may cause suppression of reflex tachycardia and increase the risk of hypotension.

There is no clinically significant interaction between nebivolol and nonsteroidal anti-inflammatory drugs (NSAIDs).

Concomitant use of nebivolol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the hypotensive effect of nebivolol.

Concomitant use of nebivolol and floctafenin is contraindicated, as there is a risk of a pronounced decrease in blood pressure or shock.

Concomitant use of nebivolol and sultoprid is contraindicated, as the risk of ventricular arrhythmia increases, especially in the “pirouette” type.

Concomitant use of nebivolol with insulin and oral hypoglycemic agents may mask the symptoms of hypoglycemia (tachycardia).

When used concomitantly, sympathomimetic agents inhibit the activity of nebivolol.

Pharmacokinetic interaction

Concomitant use of nebivolol with drugs that inhibit serotonin reuptake or other agents that biotransform with the participation of the CYP2D6 isoenzyme increases the concentration of nebivolol in blood plasma, the metabolism of nebivolol slows down, which may lead to the risk of bradycardia.

When used concomitantly with digoxin, nebivolol has no effect on the pharmacokinetic parameters of digoxin.

When nebivolol is co-administered with cimetidine, the concentration of nebivolol in the blood plasma increases.

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

When nebivolol is co-administered with nicardipine, the concentration of active substances in the blood plasma increases slightly, but this is not of clinical significance.

Concomitant use of nebivolol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

There was no clinically significant interaction between nebivolol and warfarin.

How to take, course of use and dosage

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

The average daily dose for the treatment of arterial hypertension and coronary heart disease is 2.5 mg-5 mg of Nebivolol (1/2 tablet 5 mg-1 tablet 5 mg).

Nebivolol can be used alone or in combination with other blood pressure lowering agents.

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

Treatment of chronic heart failure should begin with a slow increase in the dose until the individual optimal maintenance dose is reached. Dose selection at the beginning of treatment should be carried out according to the following scheme: maintaining intervals from one to two weeks and focusing on the patient’s tolerance to this dose: the initial dose is 1.25 mg (1/4 tablet 5 mg with a cross – shaped risk) 1 time a day, can be increased first to 2.5 – 5 mg of Nebivolol (1/2 tablet 5 mg – 1 tablet 5 mg), and then to 10 mg(2 tablets 5 mg) 1 time a day.

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

At the beginning of treatment and with each dose increase, the patient should be under medical supervision 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 exacerbation of the course of chronic heart failure).

Nebivolol is not recommended for use in patients with severe renal and/or hepatic insufficiency due to lack of experience with its use.

Overdose

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

Treatment: gastric lavage, taking activated charcoal. In case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, intravenous use of fluid and vasopressors. In case of bradycardia,0.5 – 2 mg of atropine should be administered intravenously. In the absence of a positive effect, a transvenous or intracardiac electrostimulator can be installed.

In case of AV block (grade II-III), intravenous use of beta-adrenostimulants is recommended; if they are ineffective, an artificial pacemaker should be considered. In case of heart failure, treatment begins with the introduction of cardiac glycosides and diuretics, if there is no effect, it is advisable to introduce dopamine, dobutamine or vasodilators. In bronchospasm, beta-2-adrenergic stimulants are used intravenously. For ventricular extrasystole – lidocaine (class IA antiarrhythmics cannot be administered). For hypoglycemia – intravenous dextrose (glucose) solution, for convulsions-diazepam.

Special instructions

Beta-blockers should be discontinued gradually over 10 days (up to 2 weeks in patients with coronary artery disease).

Monitoring of blood pressure and heart rate at the beginning of taking the drug should be daily.

In elderly patients, monitoring of renal function is necessary (1 time in 4-5 months). In case of exertional angina, the dose of the drug should provide a resting heart rate of 55-60 beats / min, with a load of no more than 110 beats/min

. beta-blockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats/min (see the section “Contraindications”).

When deciding whether to use Nebivolol in patients with psoriasis, the expected benefit of the drug should be carefully correlated with the possible risk of exacerbation of psoriasis.

Patients using contact lenses should take into account that the use of beta-blockers may reduce the production of tear fluid.

When performing surgical interventions, the anesthesiologist should be warned that the patient is taking beta-blockers.

Nebivolol does not affect the plasma glucose concentration in patients with diabetes mellitus. However, caution should be exercised when treating these patients, as Nebivolol may mask certain symptoms of hypoglycaemia (e. g. tachycardia) caused by the use of oral hypoglycaemic agents and insulin. Monitoring of glucose concentration in blood plasma should be carried out once every 4-5 months (in patients with diabetes mellitus).

When the thyroid gland is hyperfunctional, beta-blockers can mask tachycardia.

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

beta-blockers may increase sensitivity to allergens and the severity of anaphylactic reactions.

In smokers, the effectiveness of beta-blockers is lower compared to non-smokers.

Influence on the ability to drive motor vehicles and manage mechanisms

During treatment with Nebivolol (if side effects occur), care should be taken when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets are white or almost white in color, round, flat-cylindrical, with a chamfer and a cross-shaped risk.

Active ingredient

Nebivolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, Pregnant women as prescribed by a doctor, Nursing mothers as prescribed by a doctor

Indications

Heart Failure, Hypertension, Angina, Arrhythmia