Nebivolol pills 5mg 14pcs

Composition

1 tablet contains:

Active ingredient:

nebivolol hydrochloride – 5.45 mg (based on nebivolol-5.00

mg).

Auxiliary substances:

betadex-23.00 mg;

pregelatinized corn starch-38.40 mg;

microcrystalline cellulose-108.55 mg;

crospovidone-1.90 mg;

colloidal silicon dioxide-0.90 mg;

magnesium stearate-1.80 mg

Pharmacological action

Pharmacotherapy group:

beta-1-adrenoblocker selective.

ATX code: C07AB12

Pharmacological properties

Pharmacodynamics

Nebivolol is a cardioselective beta-1-adrenoblocker, 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, modulates 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 vasodilator effect by modulating the release of vasodilating factor (NO) from the vascular endothelium.

The antihypertensive 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 plasma renin activity).

The hypotensive effect develops after 2-5 days of regular use of the drug. A stable antihypertensive effect develops after 1-2 weeks of regular use of the drug, and in some cases-after 4 weeks, a 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 heart automatism (including in the pathological focus) and slowing of atrioventricular conduction.

Pharmacokinetics

Suction

After oral use, it is rapidly absorbed from the gastrointestinal tract. Food intake does not affect absorption, so nebivolol can be taken regardless of the time of meal. Bioavailability is about 12% in patients with “fast” metabolism (“primary passage” effect) and it can be almost complete in patients with a “slow” metabolism.

Distribution

In blood plasma, both enantiomers are predominantly bound to albumin.

Binding to plasma proteins for D-nebivolol is 98.1%, for L-nebivolol – 97.9%.

Metabolism

Nebivolol is metabolized by alicyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and are excreted as O-and N-glucuronides. The rate of metabolism of nebivolol by aromatic hydroxylation is genetically determined by an oxidative polymorphism and depends on the CYP2D6 isoenzyme. The metabolic rate does not affect the effectiveness of nebivolol.

 Deduction

It is excreted by the kidneys (38%) and through the intestines (48%). Half-life (T 1/2) in patients with “fast” metabolism: hydroxymetabolites-24 hours, nebivolol enantiomers-10 hours; in patients with “slow” metabolism: hydroxymetabolites -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;
• ischemic heart disease: prevention of angina attacks of tension;
• chronic heart failure (as part of combination therapy).

Contraindications

• hypersensitivity 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. centuries).
• the syndrome of weakness of the sinus node, including sinoauricular blockade;
• atrioventricular block degree II-III (without an artificial pacemaker);
• bronchospasm and bronchial asthma in history;
• pheochromocytoma (without the simultaneous application of a-blockers);
• metabolic acidosis;
• bradycardia (heart rate less than 50 beats/min);
• cardiogenic shock;
• severe liver dysfunction;
• severe peripheral circulatory disorders (“intermittent” claudication, Raynaud’s syndrome);
• myasthenia gravis;
• depression;
• simultaneous reception with floctafenine, sultopride (see section “Interaction with other drugs”);
• the age of 18 years (effectiveness and safety not established).

With caution

Renal insufficiency (creatinine clearance < 20 ml / min), liver function disorders, diabetes mellitus, hyperthyroidism, grade I atrioventricular block, desensitizing therapy, psoriasis, history of allergic diseases, chronic obstructive pulmonary disease, peripheral circulatory disorders, Prinzmetal angina pectoris, age over 65 years.

Side effects

the incidence of side effects, given below, were determined according to the world health organization is very often (>10%), often (more than 1% and less than 10%), uncommon (more than 0.1% and less than 1%), rarely (less than 0.01% and less than 0.1%), very rarely (less than 0.01%), the frequency is unknown (according to available data to estimate the rate of development is impossible).

From the immune system:  frequency unknown-angioedema, hypersensitivity.

From the side of the psyche:  infrequently – “nightmare” dreams, depression; very rarely-hallucinations, psychosis, confusion.

Nervous system disorders:  often – headache, dizziness, weakness, paresthesia; very rarely-fainting.

From the side of the organ of vision: frequency unknown-visual impairment, dry eyes.

From the gastrointestinal tract:  often – nausea, constipation, diarrhea; infrequently-dyspepsia, flatulence, vomiting.

From the cardiovascular system:  very often-bradycardia (in patients with CHF); often-worsening of the course of CHF, grade I atrioventricular block, orthostatic hypotension; infrequently-bradycardia, heart failure, slowing of atrioventricular conduction/atrioventricular block, marked decrease in blood pressure, progression of concomitant “intermittent” claudication; very rarely-Raynaud’s syndrome.

Skin and subcutaneous tissue disorders:  often-edema; infrequently-erythematous skin rash, pruritus; very rarely-aggravation of psoriasis; frequency unknown-alopecia.

Respiratory system disorders:  often-shortness of breath; infrequently-bronchospasm (including in the absence of obstructive pulmonary diseases in the anamnesis).

From the side of the reproductive system:  infrequently – erectile dysfunction.

Common disorders:  very often – dizziness (in patients with CHF); often-increased fatigue, edema, drug intolerance; infrequently-photodermatosis, hyperhidrosis (in patients with CHF); very rarely – cold/cyanosis of the extremities.

Interaction

Pharmacodynamic interaction

When used concomitantly with slow calcium channel blockers (BMCC) (verapamil, diltiazem), the negative effect on myocardial contractility and atrioventricular conduction increases. Intravenous use of verapamil is not recommended when nebivolol is used.

When nebivolol is used concomitantly with antihypertensive drugs, nitroglycerin, severe arterial hypotension may develop (special caution is necessary when used simultaneously with prazosin).

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). In case of abrupt withdrawal of these drugs, especially before nebivolol is discontinued, the development of “rebound” arterial hypertension (withdrawal syndrome) is possible.

Concomitant use of nebivolol and dihydropyridine-type BMCC (amlodipine, felodipine, licidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of hypotension. An increased risk of further deterioration of the pumping function of the ventricles in patients with heart failure cannot be excluded.

When used concomitantly with Class I antiarrhythmic drugs (quinidine, flecainide, disopyramide, mixelitin) and with amiodarone, it is possible to increase the negative inotropic effect and prolong the time of atrial excitation.

When used concomitantly with cardiac glycosides, there was no increase in the effect on the slowing of atrioventricular conduction.

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

There was no clinically significant interaction with nonsteroidal anti-inflammatory drugs.

Acetylsalicylic acid as an antiplatelet agent can be used simultaneously with nebivolol.

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

Concomitant use of nebivolol with insulin and hypoglycemic agents for oral use may mask some symptoms of hypoglycemia (rapid heartbeat, tachycardia).

Concomitant use with floctafenin is contraindicated: nebivolol is able to prevent compensatory reactions of the cardiovascular system associated with hypotension or shock, which may be caused by floctafenin.

Concomitant use of nebivolol with baclofen, amifostin leads to increased arterial hypotension.

When used concomitantly with sultopride, there is an increased risk of ventricular arrhythmia of the “pirouette”type.

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

Pharmacokinetic interaction.

Concomitant use of nebivolol with drugs that inhibit serotonin reuptake, or with other agents that biotransform with the participation of the CYP2D6 isoenzyme, increases the concentration of nebivolol in blood plasma, and 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 used concomitantly with cimetidine, the concentration of nebivolol in blood plasma increases (there are no data on the effect on the pharmacological effects of the drug).

Concomitant use of nebivolol and ranitidine does not affect the pharmacological 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

Inside, preferably at the same time of day, regardless of the time of eating, without chewing and washing down with a sufficient amount of liquid.

Arterial hypertension and coronary heart disease

The average daily dose of nebivolol is 2.5-5 mg once a day. For patients with renal insufficiency and patients over 65 years of age, an initial dose of nebivolol 2.5 mg/day is recommended.

If necessary, the daily dose of nebivolol can be increased to 10 mg (in one dose). The optimal therapeutic effect becomes pronounced after 1-2 weeks of taking the drug, and in some cases – after 4 weeks. Nebivolol can be used in combination therapy with other drugs that reduce blood pressure.

Chronic heart failure

The dose of nebivolol is selected gradually until the individual optimal maintenance dose is reached. It is necessary to start treatment of chronic heart failure with beta-blockers if the patient has been clinically stable for the last two weeks.

Treatment begins with a dose of 1.25 mg once a day with a gradual increase (with an interval of at least 2 weeks) to 2.5‑5 mg once a day, if necessary to a maximum dose of 10 mg once a day. The patient should be monitored by a doctor for 2 hours after taking the first dose of the drug, as well as after each subsequent increase in the dose. During the selection of the dosage regimen, in case of worsening of the course of chronic heart failure or drug intolerance, it is recommended to reduce the dose of nebivolol or stop taking it. Nebivolol should not be stopped abruptly (unless necessary), as this may lead to a temporary exacerbation of the symptoms of heart failure. If it is necessary to stop taking the drug, the cancellation is carried out gradually, halving the dose weekly.

Patients with renal insufficiency (creatinine clearance less than 20 ml / min)

The initial dose is 2.5 mg / day. If necessary, the daily dose can be increased to 5 mg. In patients with impaired renal function (creatinine clearance less than 20 ml/min), increasing the dose should be carried out with extreme caution.

Elderly patients

For patients over 65 years of age, the initial dose is 2.5 mg / day. If necessary, the daily dose can be increased to 5 mg. However, taking into account the limited experience of using the drug in elderly patients, it is necessary to be careful and conduct a thorough examination of patients over the age of 65 years. In elderly patients, there is no need to adjust the dose, so it is necessary to individually select the dose, gradually increasing it to the maximum tolerated dose.

Overdose

Symptoms: marked decrease in blood pressure, nausea, vomiting, cyanosis, bradycardia, atrioventricular block, acute heart failure, 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. With 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 atrioventricular block (grade II-III), intravenous use of beta-adrenomimetics 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. With bronchospasm, intravenous beta-2-adrenomimetics are used. In case of ventricular extrasystole, lidocaine may be prescribed (Class IA antiarrhythmics are not used). In case of convulsions, intravenous use of diazepam is recommended. With hypoglycemia, intravenous use of dextrose (glucose) is indicated.

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 vehicles and other mechanisms

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets are round, biconvex in shape from white to white with a yellowish tinge of color, with a cross-shaped risk on one side.

Active ingredient

Nebivolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets