Nebivolol pills 5mg, 28pcs

Composition

>

of 1 tab. contains:

Active ingredients:

nebivolol hydrochloride 5.45 mg, which corresponds to the nebivolol content of 5 mg

Auxiliary substances:  

lactose monohydrate – 139.91 g,

corn starch-46 mg,

microcrystalline cellulose-16.1 mg,

croscarmellose sodium-13.8 mg,

hyprolose (hydroxypropylcellulose) – 4.6 mg,

polysorbate 80-2.3 mg,

magnesium stearate-1.15 mg,

colloidal silicon dioxide-0.69 mg

Pharmacological action

Cardioselective beta-1-adrenoblocker with vasodilating properties. Nebivolol has antihypertensive, antianginal and antiarrhythmic effects.

Reduces the heart rate (HR) and lowers elevated blood pressure (BP) at rest, during exercise, reduces the final diastolic pressure of the left ventricle, improving the diastolic function of the heart, reduces the total peripheral vascular resistance, increases the ejection fraction.

Competitively and selectively blocks synaptic and postsynaptic beta-1-adrenergic receptors, making them inaccessible to catecholamines, modulates the release of endothelial vasodilating factor nitric oxide.

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

– D-nebivolol is a competitive and highly selective blocker of beta-1-adrenergic receptors (affinity for beta-1-adrenergic receptors is 293 times higher than for beta-2-adrenergic receptors);

– L-nebivolol has a vasodilating effect by modulating the release of vasodilating factor 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 the activity of renin in blood plasma).

In therapeutic doses, nebivolol does not block alpha-adrenergic receptors.

Stable antihypertensive effect develops after 1-2 weeks of regular oral use of the drug, and in some cases-after 4 weeks, a stable effect is noted after 1-2 months. This effect persists with long-term therapy.

Nebivolol improves the parameters of systemic and intracardiac hemodynamics.

Nebivolol reduces the number and severity of angina attacks and increases exercise tolerance by reducing the need for oxygen in the myocardium (reducing heart rate, reducing 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 nebivolol enantiomers are rapidly absorbed from the gastrointestinal tract. Simultaneous food intake does not affect absorption, so nebivolol can be taken regardless of the time of meal.

Bioavailability is on average 12% in patients with “fast” metabolism (“primary passage” effect) and it is almost complete in patients with a “slow” metabolism.

Distribution

In blood plasma, both nebivolol enantiomers are predominantly bound to albumin. The relationship with plasma proteins (mainly albumin) for D-nebivolol is 98.1%, for L-nebivolol – 97.9%.

Nebivolol concentrations in blood plasma are 1-30 mcg / l and are proportional to the dose. The equilibrium concentration of nebivolol in blood plasma in most patients (with “fast” metabolism) is reached within 24 hours, and for hydroxymetabolites – after several days.

Metabolism

Nebivolol is metabolized to form active metabolites by alicyclic and aromatic hydroxylation and partial N-dealkylation by isoenzymes of the CYP2D6 family, which has a genetic polymorphism. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and are excreted as O-and N-glucuroids.

The rate of metabolism of nebivolol by aromatic hydroxylation is genetically determined by an oxidative polymorphism and depends on the CYP2D6 isoenzyme.

After taking the same dose of nebivolol and achieving Css, the peak concentration of unchanged nebivolol is 23 times higher in “slow” metabolizers compared to” fast ” metabolizers.

The metabolic rate does not affect the effectiveness of nebivolol.

Given the differences in the metabolic rate, the dose of the drug should always be selected individually – patients with a” slow ” metabolism need a lower dose.

Deduction

Nebivolol is excreted in the form of O-and N-glucuronides. One week after ingestion,38% (the amount of unchanged Active ingredient is less than 0.5%) of the dose is excreted by the kidneys and 48% – through the intestines. Excretion of unchanged nebivolol through the kidneys is less than 0.5% of the dose of the drug taken orally.

In patients with “fast” metabolism, the elimination half-life (T 1/2) for hydroxymetabolites is 24 hours, and nebivolol enantiomers from blood plasma are on average 10 hours.

In patients with “slow” metabolism, these values increase by 2-5 times, amounting to 48 hours for hydroxymetabolites and 30-50 hours for nebivolol enantiomers.

The patient’s age does not affect the pharmacokinetics of nebivolol.

Indications

• Arterial hypertension.

• IHD: prevention of angina attacks of tension.

• Chronic heart failure (as part of combination therapy).

Contraindications

– Hypersensitivity to nebivolol or other components of the medication and other beta-blockers;

acute heart failure;

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

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

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

– atrioventricular block II and III degree (in the absence of an artificial pacemaker);

– bradycardia (heart rate less than 60 beats/min);

– cardiogenic shock;

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

– metabolic acidosis;

– a history of bronchospasm and bronchial asthma;

– severe peripheral circulatory disorders (intermittent claudication, Raynaud’s syndrome);

– myasthenia gravis;

– depression;

– severe liver function disorders;

– severe renal function disorders (creatinine clearance less than 20 ml/min).

– concomitant use with floctafenin, sultopride (see section “Interaction with other medicinal products”);

– intravenous use of verapamil is contraindicated against the background of nebivolol (see section” Interaction with other medicinal products”);

– lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

– breast-feeding period;

– age up to 18 years (efficacy and safety have not been established).

With caution:

– Violations of renal function (creatinine clearance (CC) of more than 20 ml/min);

– diabetes;

– hyperthyroidism;

– allergic history;

– psoriasis;

– chronic obstructive pulmonary disease;

– atrioventricular block I degree;

– Prinzmetal’s angina;

– use in elderly patients (over 65 years);

– conducting desensitizing therapies;

– disorders of peripheral blood circulation;

– disorders of the liver;

– violations of the peripheral circulation mild or moderate severity.

Side effects

the incidence of side effects, given below, were determined according to the following (classification of the world health organization): 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).

Immune system disorders:

very rare: angioedema, hypersensitivity.

Mental disorders:

infrequently: depression, “nightmare” dreams, psychosis;

very rarely: hallucinations, confusion.

Nervous system disorders:

very common: dizziness;

common: headache, dizziness, weakness, paresthesia;

very rare: fainting.

Visual disturbances:

infrequently: visual impairment;

rarely: dry eyes.

Disorders of the cardiovascular system:

very common: bradycardia;

often: worsening of CHF 1, grade I atrioventricular block, orthostatic hypotension;

infrequently: peripheral edema, bradycardia, heart failure, slowing of atrioventricular conduction/atrioventricular block, marked decrease in blood pressure, progression of concomitant “intermittent” claudication;

very rare: Reino’s syndrome.

Respiratory, thoracic and mediastinal disorders:

often: shortness of breath;

infrequently: bronchospasm (including in the absence of obstructive pulmonary diseases in the anamnesis).

Disorders of the gastrointestinal tract:

often: nausea, constipation, diarrhea;

infrequently: dyspepsia, flatulence, vomiting.

Genital and breast disorders:

infrequently: erectile dysfunction.

Skin and subcutaneous tissue disorders:

infrequently: erythematous skin rash, pruritus;

very rare: worsening of psoriasis, urticaria;

frequency unknown: alopecia.

General disorders and disorders at the injection site:

often: increased fatigue;

very rare: cold snap/cyanosis of the extremities;

infrequently: photodermatosis, hyperhidrosis.

Interaction

Pharmacodynamic interaction

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

Concomitant use of nebivolol and sultoprid is contraindicated, as there is an increased risk of ventricular arrhythmia, especially polymorphic ventricular tachycardia of the “pirouette”type, when they are used simultaneously.

Not recommended combinations

When used concomitantly with Class I antiarrhythmic drugs (quinidine, hydroquinidine, flecainide, cibenzoline, disopyramide, lidocaine, mexiletine, propafenone), it is possible to increase the negative inotropic effect and prolong the time of excitation through the atrioventricular node. Concomitant use of beta-blockers with slow calcium channel blockers (BMCC) (verapamil and diltiazem) increases the negative effect on myocardial contractility and atrioventricular conduction. Intravenous use of verapamil with nebivolol is contraindicated. When used concomitantly with antihypertensive agents of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine), the course of heart failure may worsen 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.

Combinations that should be used with caution

When used concomitantly with class III antiarrhythmic agents (amiodarone), the effect on the time of passage through the atrioventricular node may increase.

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

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

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

Combinations to take into account

When nebivolol is co-administered with cardiac glycosides, atrioventricular conduction may slow down. Nebivolol does not affect the pharmacokinetic parameters of digoxin. Concomitant use of nebivolol and dihydropyridine-type BMCC (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of hypotension. An increased risk of further reduction in myocardial contractility in patients with heart failure cannot be excluded.

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

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

There is no clinically significant interaction between nebivolol and nonsteroidal anti-inflammatory drugs (NSAIDs). Acetylsalicylic acid as an antiplatelet agent can be used simultaneously with nebivolol. When used concomitantly, sympathomimetic agents may inhibit the activity of beta-blockers.

Theoretically, co-use of mefloquine with nebivolol may lead to prolongation of the QT interval.

Pharmacokinetic interactions

When nebivolol is used in combination with drugs that inhibit serotonin reuptake, or other drugs that are metabolized with the participation of the CYP2D6 isoenzyme (for example, paroxetine, fluoxetine, thioridazine, quinidine), nebivolol metabolism slows down, nebivolol concentration in blood plasma increases, which can lead to the risk of bradycardia and other side effects.

Concomitant use with cimetidine may increase the concentration of nebivolol in blood plasma (there are no data on the effect on the pharmacological effects of the drug).

Concomitant use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

Rifampicin increases the metabolism of nebivolol.

When nebivolol is co-administered with nicardipine, the concentration of active substances in the blood plasma slightly increases without changing the clinical effect.

Concomitant use of 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, at the same time, regardless of the time of eating, without chewing and with a sufficient amount of liquid.

A 5 mg or 10 mg tablet can be divided into two or four equal parts according to the cross-shaped risk.

Arterial hypertension and coronary heart disease

The average daily dose is 2.5-5 mg (1-2 tablets of 2.5 mg; 1/2-1 tablet of 5 mg) 1 time a day.

The optimal antihypertensive effect is achieved after 1-2 weeks of treatment, in some cases-after 4 weeks.

If necessary, the dose can be increased to a maximum daily dose of 10 mg. Possible use of the drug Nebivolol in monotherapy or in combination with other antihypertensive agents.

Elderly patients: for patients over 65 years of age, the initial dose is 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg). 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 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.

Patients with renal insufficiency (creatinine clearance greater than 20 ml / min): the initial dose is 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg). If necessary, the daily dose can be increased to 5 mg. Increasing the dose in such patients should be carried out with extreme caution.

Chronic heart failure (CHF)

Treatment of stable CHF should begin with a gradual increase in the dose until the individual optimal maintenance dose is reached. Patients should not have experienced an attack of acute heart failure in the last 6 weeks. It is recommended to carry out treatment under the close supervision of a doctor.

Patients taking diuretics, cardiac glycosides, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor antagonists should have their dosage stabilized 2 weeks before starting therapy with the drug Nebivolol.

It is necessary to start treatment of CHF with beta-adrenergic blockers if the patient has been in a clinically stable condition for the last 2 weeks.

Dose selection at the beginning of therapy should be carried out according to the following scheme, maintaining intervals from 1 to 2 weeks: the dose of 1.25 mg per day (1/2 tablet of 2.5 mg or 1/4 tablet of 5 mg) can be increased first to 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg), then to 5-10 mg per day.

Each dose increase should be carried out after at least 1-2 weeks, depending on the individual tolerance of the drug.

At the beginning of treatment and with each dose increase, the patient should be under medical supervision for at least 2 hours to make sure 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).

The maximum daily dose of nebivolol is 10 mg once a day.

Regular monitoring of blood pressure, heart rate, and symptoms of chronic heart failure is recommended during titration.

During titration, if the course of CHF worsens or the drug is intolerant, it is recommended to reduce the dose of the drug. Nebivolol or, if necessary, immediately stop taking it (in case of severe arterial hypotension, with worsening of CHF with acute pulmonary edema, in case of cardiogenic shock, symptomatic bradycardia or atrioventricular block). Treatment of stable CHF is usually long-term. Drug treatment Nebivolol is not recommended to be stopped abruptly (unless it is necessary), as this may lead to a temporary exacerbation of the course of CHF. If it is necessary to stop taking the drug, the cancellation is carried out gradually, reducing the dose by half over the course of a week.

Overdose

Symptoms: marked decrease in blood pressure, severe bradycardia, acute heart failure, atrioventricular block, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, convulsions, coma, nausea, vomiting, hypoglycemia, cyanosis.

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 fluids and vasopressors. Artificial ventilation may be necessary.

With severe bradycardia,0.5-2 mg of atropine should be administered intravenously; in the absence of a positive effect, an artificial pacemaker can be set up.

Intravenous use of beta-adrenomimetics is recommended for atrioventricular block (grade II-III). The effect of beta-blockers can be neutralized by slow intravenous use of isoprenaline, starting with a dose of 5 mcg / min, or dobutamine, starting with a dose of 2.5 mcg / min, until the desired effect is achieved. In severe cases, isoprenaline can be combined with dopamine.

If these doses do not produce the desired effect, intravenous use of 50-100 mcg/kg of glucagon should be considered. If necessary, the injection should be repeated after 1 hour, followed by intravenous use of 70 mcg/kg/h of glucagon. If they are ineffective, you should consider setting up an artificial pacemaker.

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.

When bronchospasm is used intravenously beta-2-adrenomimetics.

For ventricular extrasystole – lidocaine (class IA antiarrhythmics cannot be administered).

For convulsions-intravenous use of diazepam.

For hypoglycemia, intravenous dextrose (glucose) may be indicated.

Special instructions

Abrupt discontinuation of beta-blockers is unacceptable (with abrupt discontinuation of treatment, “withdrawal” syndrome may develop), treatment should be stopped gradually if possible, reducing the dose for 10 days (1-2 weeks in patients with coronary heart disease).

Monitoring of patients taking beta-blockers includes monitoring of their heart rate and blood pressure (at the beginning of use – daily, then once every 3-4 months).

In elderly patients, monitoring of renal function is necessary (1 time in 4-5 months).

With stable angina, the selected dose 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”).

Beta-blockers should be used with caution in the following groups of patients::

– with peripheral circulatory disorders,

– with atrioventricular block of the first degree, since beta-blockers negatively affect the time of pulse conduction;

– with Prinzmetal angina pectoris due to unobstructed alpha-receptor-mediated vasoconstriction of the coronary artery: beta-adrenergic antagonists can increase the number and duration of angina attacks.

Beta-blockers should be used with caution in patients with chronic obstructive pulmonary disease, as increased bronchospasm may occur.

Beta-blockers should not be used in patients with untreated chronic heart failure until the condition has stabilized.

Treatment of chronic heart failure with nebivolol is carried out against the background of stable indicators of the cardiovascular system no earlier than 6 weeks after the end of the decompensation period.

Nebivolol can be used for the treatment of chronic heart failure simultaneously with thiazide diuretics, digoxin, ACE inhibitors or angiotensin II receptor antagonists.

In smoking patients, the effectiveness of beta-blockers is lower than in non-smokers.

Nebivolol has no effect on glucose concentration in patients with diabetes mellitus, but nebivolol may mask signs of hypoglycemia (tachycardia, palpitation) caused by the use of hypoglycemic agents. In patients with diabetes mellitus, glucose concentration monitoring should be performed once every 4-5 months.

Beta-blockers should be used with caution in patients with increased thyroid function due to the fact that the influence may mask the clinical signs of hyperthyroidism, such as tachycardia.

Abrupt withdrawal of the drug may cause an exacerbation of the symptoms of the disease and the development of a thyrotoxic crisis.

Nebivolol can be used in patients with pheochromocytoma only when taking alpha-blockers together.

Beta-blockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Nebivolol may cause a severe reaction to a number of allergens when administered to patients with a history of severe anaphylactic reactions to these allergens. Such patients may not respond to the usual doses of epinephrine (epinephrine) used to treat anaphylactic shock.

When deciding whether to prescribe the drug to patients with psoriasis, the expected benefit of using the drug and the possible risk of exacerbation of psoriasis should be carefully correlated.

Patients who use contact lenses should take into account that against the background of treatment with beta-blockers, tear fluid production may decrease.

If a patient needs to undergo surgery during Nebivolol therapy, please inform the anaesthetist surgeon about the nature of the therapy being performed.

Continued beta-blocking reduces the risk of arrhythmia during anesthesia and intubation. If the preparation for surgery involves interrupting the beta-blocker, you should stop taking beta-adrenergic antagonists at least 24 hours before surgery.

Anaesthetics that cause myocardial depression should be used with caution.

Vagal reactions in the patient can be prevented by intravenous use of atropine.

Influence on the ability to drive vehicles and mechanisms:Studies of the effect of nebivolol on the ability to drive vehicles and mechanisms have not been conducted. Pharmacological studies have shown that nebivolol has no effect on the rate of psychomotor reactions. Due to the possible occurrence of side effects, such as dizziness and increased fatigue, during treatment with the drug, 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.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Nebivolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

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

Indications

Arrhythmia, Angina, Hypertension, Heart Failure