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

Excipients: lactose monohydrate 147.15 mg, microcrystalline cellulose 35.00 mg, povidone 6.00 mg, croscarmellose sodium 4.00 mg, polysorbate-80 0.40 mg, magnesium stearate 2.00 mg.

Description:tablets white or almost white, round, flat-cylindrical, with a facet and a cross-shaped risk on one side.

Pharmacotherapeutic group:beta-blocker selective.

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Cardioselective beta-blocker with vasodilating properties. Nebivolol has antihypertensive, anti-anginal and antiarrhythmic effect. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively block postsynaptic beta-adrenergic receptors, making them inaccessible to catecholamines, modulating the release of the endothelial vasodilating factor of nitric oxide. Nebivolol is a racemate consisting of two enantiomers: DNebivolol (SRRRnebivolol) and LNebivolol (RSSS- nebivolol), combining two pharmacological actions:

- D-nibilol is a competitive and highly selective beta-blocker-adrenergic blocker;

- LNebivolol has a mild vasodilating effect due to the modulation of vasodilating factor release from the vascular endothelium.

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

A stable antihypertensive 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 retardation of atrioventricular conduction.

Pharmacokinetics:

Suction

After oral administration, both enantiomers of nebivolol are rapidly absorbed from the gastrointestinal tract. Eating does not affect absorption. Bioavailability averages 12% in patients with "fast" metabolism (the effect of "primary transmission") and is almost complete in patients with "slow" metabolism.

Distribution

Clearance in the blood plasma in most patients (with a "fast" metabolism) is achieved within 24 hours, and for hydroxy metabolites - in a few days. Concentrations in blood plasma of 1-30 mcg / l are proportional to the dose.

Connection with blood plasma proteins (mainly with albumin) for DThe nebivolol is 98.1%, for L- nebivolol - 97.9%.

Metabolism

Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites. Metabolism of nebivolol occurs by alicyclic and aromatic hydroxylation, partial N-dealkylation and glucuronation, in addition, glucuronides of hydroxy metabolites are formed. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the isoenzyme CYP2D6.

Excretion

One week after taking 38% (the amount of unchanged active substance is less than 0.5%), the dose is excreted by the kidneys and 48% by the intestine. In patients with "fast" metabolism, the half-life of nebivolol enantiomers from plasma is on average 10 hours. In patients with "slow" metabolism, these values increase 3-5 times.

In patients with "fast" metabolism, the values of the half-life of hydroxy metabolites of both enantiomers from plasma are an average of 24 hours, in patients with "slow" metabolism these values are approximately 2-fold increased. Given the difference in metabolic rate, the dose of the drug should always be selected individually: patients with "slow" metabolism require a smaller dose. Pharmacokinetic parameters do not have age and sex differences.

Indications:

- arterial hypertension;

- ischemic heart disease: prevention of angina pectoris attacks;

chronic heart failure (as part of combination therapy).

Contraindications:

- increased sensitivity to nebivolol or other components of the drug and other beta-blockers;

- severe violations of liver function;

- acute heart failure;

- chronic heart failure in the stage of decompensation (requiring inotropic therapy);

- cardiogenic shock;

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

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

- bronchospasm and bronchial asthma in history;

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

- metabolic acidosis;

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

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

- depression;

- severe violations of peripheral circulation ("intermittent" lameness, Raynaud's syndrome);

- myasthenia gravis;

- simultaneous administration with floktaphenin, sultopride;

- age under 18 years (effectiveness and safety not established);

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

Carefully:

impaired renal function (creatinine clearance (CC) less than 20 ml / min), liver dysfunction, diabetes mellitus, hyperthyroidism, desensitizing therapy,weighed allergic anamnesis, psoriasis, peripheral circulatory disorders, atrioventricular blockade of I degree, prinzmetal angina, chronic obstructive pulmonary disease, use in elderly patients (over 65 years old).

Pregnancy and lactation:

Nebivolol can have harmful effects on the course of pregnancy, on the fetus and the newborn. Reduction of placental perfusion under the action of beta-blockers can cause a delay in fetal development, fetal death, miscarriage and premature birth. In newborns, there may be a bradycardia, a decrease in blood pressure, hypoglycemia and respiratory paralysis.

Use during pregnancy is possible only if the expected benefit for the mother exceeds the potential risk to the fetus. Reception of the drug Nebivolol must be discontinued 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict observation of newborns within 48-72 hours after childbirth. Nebivolol excreted in breast milk. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, at the same time, regardless of the time of ingestion, without chewing and drinking with a sufficient amount of liquid.

Arterial hypertension and ischemic heart disease

The average daily dose is 2.5-5 mg (1/2 tablet - 1 tablet of 5 mg) 1 time / day. The optimal therapeutic 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 (2 tablets of 5 mg at one time). The maximum daily dose is 10 mg (2 tablets of 5 mg each).

It is possible to use the drug in monotherapy or in combination with other antihypertensive drugs.

Patients with renal insufficiency:

The initial dose is 2.5 mg (1/2 tablet 5 mg each) 1 time / day. If necessary, the daily dose can be increased to 5 mg.

Patients with hepatic insufficiency:

Experience with nebivolol in patients with liver failure is limited, so the drug should be administered with caution. For patients with mild to moderate hepatic insufficiency, the recommended initial dose is 2.5 mg (1/2 tablets 5 mg) 1 time / day, if necessary, the daily dose of the drug can be increased to 5 mg.The effects of nebivolol on patients with severe hepatic insufficiency have not been studied, so the appointment of nebivolol in severe hepatic insufficiency is contraindicated.

Older patients:

For patients over 65 years of age, the initial dose is 2.5 mg (1/2 tablet 5 mg each). 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, nebivolol it is necessary to appoint with caution and to conduct a thorough examination of patients over the age of 65 years.

Chronic heart failure

Treatment of stable chronic heart failure should begin with a gradual titration dose to achieve an individual optimal maintenance dose. Patients should not have attacks of acute heart failure within the last 6 weeks. It is recommended to carry out treatment under close supervision of a doctor.

Patients who take diuretics, cardiac glycosides, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, drug doses should be stable for at least two weeks prior to the onset of Nebivolol therapy.

Begin the treatment of chronic heart failure with beta-adrenoreceptor blockers in a clinically stable patient for the past 2 weeks. Selection of the dose at the beginning of therapy should be carried out according to the following scheme, maintaining 2-week intervals: the initial dose of 1.25 mg / day (1/4 tablets of 5 mg) can be increased to 2.5 mg / day (1 / 2 tablets of 5 mg), then - up to 5-10 mg / day (1-2 tablets of 5 mg). The maximum daily dose is 10 mg (2 tablets of 5 mg each).

Each dose increase should be carried out not later than 2 weeks, depending on the individual tolerability of the drug.

The beginning of therapy and each increase in the dose of the drug should be done under strict supervision of the doctor, at least during the first 2 hours. During titration, regular monitoring of blood pressure, heart rate and symptoms of chronic heart failure is recommended.

Treatment of stable chronic heart failure is usually prolonged. Treatment with nebivolol is not recommended to be discontinued sharply, as this may lead to a temporary exacerbation of the course of chronic heart failure.If it is necessary to stop taking the drug, the cancellation is carried out gradually, reducing the dose within a week, twice.

Patients with renal insufficiency:

In mild and moderate renal impairment (creatinine clearance of 20 ml / min) the need for dose adjustment is absent, so it is necessary to select a dose individually, gradually increasing to the maximum tolerated. No experience with nebivolol in patients with severe renal dysfunction (creatinine clearance less than 20 mL / min), however its reception in these patients is not recommended.

Patients with hepatic insufficiency:

Experience of nebivolol in patients with liver failure is limited, and the drug should be used with caution in patients with liver disease of mild to moderate severity, a dose should be adjusted individually, gradually increasing to the maximum tolerated daily dose can optionally be increased up to 5 mg / day (1 tablet of 5 mg each). The effects of nebivolol on patients with severe hepatic insufficiency have not been studied, so the appointment of nebivolol in severe hepatic insufficiency is contraindicated.

Older 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.

Side effects:

The frequency of side effects listed below was determined according to the classification of the World Health Organization: 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 reports.

Disturbances from the nervous system: often: headache, dizziness, fatigue, weakness, paresthesia; infrequently-, depression, "nightmarish" dreams, confusion, insomnia; rarely', fainting, hallucinations.

Disorders from the gastrointestinal tract: often: nausea, constipation, diarrhea; infrequently: dyspepsia, flatulence, vomiting.

Disorders from the cardiovascular system: often: peripheral edema; infrequently: bradycardia, heart failure, atrioventricular blockade, orthostatic hypotension, Raynaud's syndrome, cardiac rhythm disorders, cardialgia, worsening of chronic heart failure, marked decrease in blood pressure.

Disturbances from the skin and subcutaneous tissues: infrequently: skin rash erythematous, itchy skin; rarely', aggravation of psoriasis; in some cases: angioedema, alopecia.

Disturbances from the respiratory system: often: shortness of breath; infrequently: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis).

Other:

Infrequently: impaired vision, impotence, photosensitivity reactions, hyperhidrosis; Rarely: dryness of the eye mucosa.

Overdose:

Symptoms:

A marked decrease in blood pressure, pronounced bradycardia, acute heart failure, atrioventricular blockade, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, convulsions, coma, nausea, vomiting, hypoglycemia, cyanosis. Treatment:

Gastric lavage, reception of 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, intravenous 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 inserted.When atrioventricular blockade (H-S st.) Is recommended intravenous beta-adrenostimulyatorov, if their inefficiency should consider the issue of an artificial pacemaker. With heart failure treatment begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to administer dopamine, dobutamine or vasodilators. When bronhospazme intravenously used betag-adrenomimetiki. When ventricular ekstrasistolii - lipodain (do not inject antiarrhythmics IA class). With convulsions - intravenous diazepam. In hypoglycemia, intravenous dextrose (glucose) can be indicated.

Interaction:

Pharmacodynamic interaction

With simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) increases the negative effect on myocardial contractility and atrioventricular conductivity. Contraindicated intravenous administration of verapamil against nebivolol.

With the simultaneous use of nebivolol with antihypertensive drugs, nitroglycerin may develop severe arterial hypotension (special caution is necessary when combined with prazosin).

Simultaneous use of nebivolol and BCCC dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of developing arterial hypotension.

It is impossible to exclude the possibility of further reducing myocardial contractility in patients with chronic heart failure.

With simultaneous use with antihypertensive agents of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of heart failure by reducing the sympathetic tone (decreased 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 simultaneous use with antiarrhythmic drugs I class (quinidine, hydroquinidine, flecainide, cibenzoline, disopyramide, lidocaine, mexiletine, propafenone) and with amiodarone, an increase in the negative inotropic effect and an extension of the excitation time to the atria are possible.

With the simultaneous use of nebivolol with cardiac glycosides, atrioventricular conduction may be slowed.

Simultaneous use of nebivolol and funds 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.

Acetylsalicylic acid as antiplatelet agent can be used concomitantly with nebivolol.

The simultaneous use of tricyclic antidepressants, barbiturates and phenothiazine derivatives, anxiolytics, hypnotics, ethanol can enhance the anti-hypertensive effect of nebivolol.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, with the simultaneous use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (palpitation, tachycardia) can be masked.

Contraindicated simultaneous reception with floktapheninom: nebivolol is able to prevent compensatory reactions of the cardiovascular system associated with arterial hypotension or shock, which can be caused by floktaphenin. Simultaneous reception of nebivolol with baclofen, amifostine leads to an increase in arterial hypotension.

Contraindicated simultaneous use with sultopride in connection with an increased risk of ventricular arrhythmia of the type "pirouette".

Pharmacokinetic interaction

When used simultaneously with drugs that inhibit the reuptake of serotonin, or other drugs biotransforming with the participation of isoenzyme CYP2D6, the concentration of nebivolol in the blood plasma increases, the metabolism of nebivolol slows down, which can lead to the risk of bradycardia.

With simultaneous application nebivolol did not affect the pharmacokinetic parameters of digoxin.

With simultaneous use with cimetidine, the concentration of nebivolol in the blood plasma increases (there is no evidence of an effect on the pharmacological effects of the drug). The simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

Rifampicin enhances the metabolism of nebivolol.

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increased slightly (which has no clinical significance). With the simultaneous use of nebivolol and ethanol, furosemide or hydrochlorothiazide, there is no change in the pharmacokinetic parameters of nebivolol. Clinically significant interactions of nebivolol and warfarin have not been established. With the simultaneous use of sympathomimetic drugs suppress the pharmacological activity of nebivolol.

Special instructions:

It is unacceptable to abruptly stop taking beta-blockers (if the treatment is abruptly discontinued), treatment should be stopped as soon as possible, reducing the dose within 10 days (1-2 weeks in patients with ischemic heart disease).

Treatment of chronic heart failure with nebivolol is carried out against the background of stable cardiovascular parameters, not earlier than 6 weeks after the end of the decompensation period. Nebivolol can be used to treat chronic heart failure concomitantly with thiazide diuretics, digoxin, ACE inhibitors or angiotensin II receptor antagonists.

With stable angina, the chosen dose should provide a heart rate at rest in the range of 55-60 beats / min, with a load of no more than 110 beats / minute. Beta-adrenoblockers can cause bradycardia: the dose should be reduced if the heart rate is less than 55-60 beats / min.

Beta-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease, since it is possible to strengthen bronchospasm.

In smoking patients, the effectiveness of beta-blockers is lower.

Nebivolol has no effect on glucose concentration in patients with diabetes, but nebivolol may mask the signs of hypoglycemia (tachycardia, palpitation) caused by the use of hypoglycemic agents.

Beta-adrenoblockers should be used with caution in patients with increased thyroid function due to the fact that the clinical signs of hyperthyroidism, such as tachycardia, can be masked by nebivolol. Abrupt withdrawal of the drug may cause an exacerbation of the symptoms of the disease and the development of thyrotoxic crisis.

Control of patients taking beta-blockers includes monitoring heart rate and blood pressure (at the beginning of the procedure - every day, then once every 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 time in 4 -5 months.).

In elderly patients it is recommended to follow the function of the kidneys (once every 4-5 months). Nebivolol can enhance the symptoms of peripheral circulatory disorders. Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Nebivolol can be the cause of a severe reaction to a number of allergens when administered to patients who have a history of severe anaphylactic reaction to these allergens. Such patients may not respond to the usual doses of epinephrine (adrenaline) used to treat anaphylactic shock.

When deciding whether to prescribe a drug for patients with psoriasis, the expected benefits 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-adrenoblockers, tear production can be reduced.

If during therapy with the drug Nebivolol the patient is required to undergo a surgical procedure, it is necessary to inform the surgeon and / or anesthesiologist about the nature of the therapy.

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

treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg.

For 7, 10 or 14 tablets in a contour mesh package; 1, 2 or 4 contour packs of 7 tablets, 1 or 3 contour packs of 10 tablets each, 1 or 2 contour packs of 14 tablets together with the instructions for use are placed in a cardboard box. For 28 tablets in a can of polymer with a lid. Each bank along with the instruction for use is placed in a cardboard pack.

Packaging:(10) - packings, cellular, outline (1) - packs, cardboard
(10) - packings, cellular, outline (3) - packs, cardboard
(14) - packings, cellular, outline (1) - packs, cardboard
(14) - packings, cellular, outline (2) - packs, cardboard
(28) - polymer cans (1) - cardboard packs
(7) - packings, cellular, planimetric (1) - packs, cardboard
(7) - packings, cellular, outline (2) - packs, cardboard
(7) - packings, cellular, outline (4) - packs, cardboard

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002567

Date of registration:06.08.2014

The owner of the registration certificate:Berezovsky Pharmaceutical Plant, ZAO Berezovsky Pharmaceutical Plant, ZAO Russia

Manufacturer: & nbsp

Berezovsky Pharmaceutical Plant, ZAO Russia

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Nebivolol (Nebivolol)