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

Excipients: lactose monohydrate - 139.91 mg, corn starch - 46.0 mg, cellulose microcrystalline - 16,10 mg, croscarmellose sodium - 13.80 mg, giprolose (hydroxypropylcellulose) 4.60 mg, ionisorb 80 - 2.30 mg, magnesium stearate -1.15 mg, silicon dioxide colloid - 0.69 mg .

Description:Round flat-cylindrical tablets of white or almost white color with a facet and a risk.

Pharmacotherapeutic group:β1-blocker selective.

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a cardioselective β1-adrenergic blocker of the third generation with vasodilating properties. It has antihypertensive, anti-arrhythmic and antiarrhythmic effects. Nebivolol reduces heart rate (heart rate) and lowers blood pressure (BP) at rest and under physical exertion, reduces the final diastolic pressure of the left ventricle, improves the diastolic function of the heart, reduces the overall peripheral vascular resistance, increases the ejection fraction. Competitively and selectively blocks synaptic and postsynaic β1-adrenoceptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide (N0). Nebivolol is a racemate consisting of two enantiomers: SRRRNebivolol (Dnebivolol) and RSSSnebnvolol (LNebivolol), combining two pharmacological actions:

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

- LNebivolol renders vasodilator action at the expense of modulation release of the vasodilating factor (N0) from the vascular endothelium.

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

Antihypertensive effect occurs on the 2-5 day of treatment, stable effect is observed after 1-2 months. This effect persists with long-term treatment.

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

Pharmacokinetics:

Suction

After oral administration, both enantiomers are rapidly absorbed. Eating does not affect suction, so nebivolol can be taken regardless of the time of ingestion. Bioavailability of the ingested isbivolol is on average 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%.

Metabolism

Metabolized with the formation of active metabolites by alicyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy- and amino-derivatives are conjugated with glucuronic acid and are excreted in the form of O- and N-glucuronides. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the isoenzyme CYP2D6.

Excretion

38% of the dose taken internally, excreted by the kidneys (the amount of unchanged nebivolol is less than 0.5%) and 48% through the intestine.

In patients with "fast" metabolism, the half-life (T1/2) gdroksi-metabolites - 24 h, enantiomers nebivolol - 10 h. In patients with a "slow" metabolism T1/2 hydroxymetabolites - 48 h, enantiomers of nebivolol - 30-50 h.

Indications:

- arterial hypertension;

- ischemic heart disease: prevention of angina pectoris attacks;

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

Contraindications:

- hypersensitivity to nebivolol or any 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 Pg.);

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

- atrioventricular blockade II and III degree (in the absence of an artificial pacemaker);

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

- cardiogenic shock;

- pheochromocytoma (without simultaneous application of a-adrenoblockers);

- metabolic acidosis;

- severe liver dysfunction;

- bronchial asthma and bronchospasm in the anamnesis;

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

- myasthenia gravis, muscle weakness;

- depression;

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

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

- simultaneous administration with floktaphenin, sultopride (see section "Interaction with other drugs");

- intravenous administration of verapamil against the background of nebivolol;

- severe renal insufficiency (creatinine clearance (CK) <20 mL / min).

Carefully:

- diabetes;

- hyperthyroidism;

- weighed allergic anamnesis, conducting desensitizing therapy, psoriasis;

- chronic obstructive pulmonary disease;

- atrioventricular blockade of the 1st degree;

- angina of Prinzmetal;

- age over 65 years.

Pregnancy and lactation:

In pregnancy Nebivolol appoint only on strict indications,when the benefit to the mother exceeds the risk to the fetus (due to the possibility of delaying the development and growth of the fetus, fetal death, premature birth, as well as the development of a newborn bradycardia, lowering blood pressure, hypoglycemia and respiratory paralysis). Treatment should be interrupted for 48-72 hours before childbirth. In cases where this is not possible, it is necessary to monitor uteroplacental blood flow and fetal growth, and to ensure strict observation of newborns within the first three days after delivery.

Studies in animals have shown that piebifolium is excreted in breast milk. If you need to take the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Nebivolol tablets are taken orally, once a day, preferably 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 of Piebivolol (1/2 tablets 5 mg - 1 tablet 5 mg) once a day.Clinically significant effect is observed after 1-2 weeks of treatment, and in some cases, 4 weeks. It is possible to use the drug in monotherapy or as part of a combination therapy.

If necessary, the daily dose can be increased to a dose of 10 mg (2 tablets of 5 mg at a time).

The maximum daily dose is 10 mg.

In patients with renal insufficiency (CC> 20 ml / min), as well as in patients older than 65 years, the recommended initial dose is 2.5 mg (1/2 tablets 5 mg) of Peprovolol per day. If necessary, the daily dose can be increased to 5 mg (1 tablet of 5 mg).

There is no experience with the use of iebivolol in patients with severe renal insufficiency (CC <20 ml / min), so its use in such patients is not recommended.

Chronic heart failure (CHF)

Treatment of CHF should begin with a gradual 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 in stages, while maintaining intervals of one to two weeks and focusing on the tolerance of this dose to the patient, according to the following scheme: initial dose of 1.25 mg of iebivolol (1/4 tablets 5 mg - another dosage form: 5 mg tablets with a cross-shaped risk) I once a day,can be increased first to 2.5 - 5 mg of the drug Nebivolol (1/2 tablets 5 mg - 1 tablet 5 mg) once a day, and then - up to 10 mg (2 tablets of 5 mg once a day) once a day.

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

At the beginning of treatment and at each dose increase, the patient should be under at least 2 hours under medical supervision to confirm that the clinical condition remains stable. During the selection of a dose, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.

During dose adjustment in case of flow of CHF deterioration or intolerance to the drug it is recommended to reduce the dose of the drug or, if necessary, immediately stop taking it (in the case of pronounced hypotension, in CHF current worsening with acute pulmonary edema in case of cardiogenic shock, symptomatic bradycardia or atrioventricular (AV) blockade).

Treatment with drug Nebivolol It is not recommended to stop abruptly (if this is not necessary), as this can lead to a transient deterioration in the course of CHF. If necessary, the dose should be reduced gradually (half every week).

For patients receiving medication for cardiovascular disease, including diuretics, digoxin, angiotepin-converting enzyme inhibitors and / or angiotensin II receptor antagonists, prior to initiation of drug treatment Nebivolol should stabilize the dose of these drugs in the past two weeks.

In patients with mild and moderate renal insufficiency (CK> 20 ml / min), as well as in patients older than 65 years, there is no need to adjust the dose, since it is necessary to select the dose individually, gradually increasing to the maximum tolerable.

There is no experience with the use of iebivolol in patients with severe renal insufficiency (CC <20 ml / min), so its use in such patients is not recommended.

Side effects:

The incidence of adverse events is classified according to the recommendations

World Health Organization:

very often -> = 1/10 (> 10%);

often from> = 1/100 to <1/10 (> 1% and <10%);

infrequently from> = 1/1000 to <1/100 (> 0.1% and <1%);

rarely from> = 1/10000 to <1/1000 (> 0.01% and <0.1%);

very rarely - <1/10000 (<0.01%);

frequency is unknown - frequency can not be estimated based on available data.

From the nervous system
Often - headache, dizziness, fatigue, weakness, paresthesia. Infrequently - depression, "nightmarish" dream, confusion, decreased ability to concentrate, drowsiness, insomnia.
Very rarely - fainting, hallucinations.

From the digestive system

Often, nausea, constipation, diarrhea, dryness of the oral mucosa.

Infrequent - dyspepsia, flatulence, vomiting.

From the side of the cardiovascular system Often - peripheral edema.

Infrequently - bradycardia, congestive heart failure, exacerbation of chronic heart failure, atrioventricular block, slow atrioventricular conduction, reduced blood pressure, orthostatic hypotension, cardiac arrhythmias, false angina, exacerbation of "intermittent" claudication, Raynaud's syndrome.

From the skin and subcutaneous tissues

Infrequent - skin rash erythematous nature, itchy skin.

Very rarely - exacerbation of psoriasis, photodermatosis, increased sweating. From the immune system

The frequency is unknown - angioedema, hypersensitivity.

From the respiratory system Often - shortness of breath.

Infrequent - bronchospasm (including, in the absence of obstructive pulmonary disease in the anamnesis), rhinitis.

From the side of the reproductive system Infrequent - erectile dysfunction.

From the sense organs

Infrequent - impaired vision, "dryness" of the eyes.

Other

The frequency is unknown - alopecia.

Overdose:

Symptoms

The pronounced decrease in blood pressure, nausea, vomiting, cyanosis, pronounced bradycardia, AV blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, acute heart failure, cardiac arrest, hypoglycemia, convulsions.

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 should be administered intravenously, 0.5-2 mg of atropine, in the absence of a positive effect, a transvenous or virotricardic electrostimulator can be used. When AV blockade (II-III It is recommended intravenous administration of P-adrenomimetics, if their ineffectiveness should be considered the question of staging 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. With bronchospasm, Pr-adrenomimetics are administered intravenously. With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class). When hypoglycemia - intravenous solution of dextrose (glucose), with convulsions - intravenously diazepam.

Interaction:

Pharmacodynamic interaction

Contraindicated simultaneous use of nebivolol and floktaphenina, as there is a threat of severe arterial hypotension or shock.

Contraindicated simultaneous use of nebivolol and sulgoprid, as the risk of ventricular arrhythmia, especially ventricular tachycardia such as pirouette, increases.

With the simultaneous use of (3-adrenoblockers with blockers of "slow" calcium channels (BCC) (razorpalil and diltiazem) the negative effect on myocardial contractility and AV conductivity. Contraindicated intravenous administration of verapamil against the background of nebivolol.

Simultaneous use of nebivolol and BCCC dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of developing arterial hypotension. It can not be ruled out that there is an increased risk of further reduction of myocardial contractility in patients with heart failure.

When simultaneous application of nebivolol from antihypertensive agents, nitroglycerin or BCCC can develop severe hypotension (special caution is necessary when combined with prazosin).

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

When simultaneous application of nebivolol from antihypertensive drugs central action (clonidine, guaifacin, 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 the simultaneous use of nebivolol with anti-arthritis preparations of the first class (chiidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, Mexico, propafenone) and with amiodarone, an increase in the negative inotropic effect and an extension of the excitation time to the atria are possible.

Simultaneous use of nebivolol with cardiac glycosides may cause a slowdown AV conductivity. However, the results of clinical studies of nebivolol showed no indication of this interaction.

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 have not been established.

Acetylsalicylic acid as an apyaggregant agent can be used concomitantly with nebivolol.

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

With the simultaneous use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia, palpitations) can be masked.

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

Pharmacokinetic interaction

With the simultaneous use of nebivolol with drugs that inhibit the reuptake of serotonin, or other means, biotransforming with the participation of isoenzyme CYP2D6 (e.g., paroxystine, fluoxetine, thioridazine, chiidine), 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 use with digoxin nebivolol no impact on the pharmacokinetic parameters of digoxin.

With the simultaneous use of nebivolol with cimetidine, the concentration of nebnvolol in the blood plasma increases.

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

With the simultaneous use of nebivolol with nicardipine, the concentrations of both substances in the blood plasma increase slightly without changing the clinical effect.

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

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

Special instructions:

Inadmissible abrupt discontinuation of beta-adrenoblockers, the abolition of β-blockers should be carried out gradually, within 10 days (up to 2 weeks in patients with coronary 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.

P-blockers 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 nebnvolol in patients with psoriasis, the intended use of the drug and the possible risk of exacerbation of psoriasis should be carefully correlated.

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

When conducting surgical procedures, an anesthesiologist should be warned that the patient is taking beta-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, since nebivolol can mask certain symptoms of hypoglycemia (tachycardia, heart palpitations) caused by the use of hypoglycemic agents for ingestion and insulin. In patients with diabetes mellitus, the blood glucose concentration should be monitored once every 4-5 months.

With hyperthyroidism, β-adrenoblockers can mask tachycardia.

P-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 severity of anaphylactic reactions.

The effectiveness of β-blockers in smokers is lower than in non-smoking patients.

Effect on the ability to drive transp. cf. and fur:The influence of nebivolol on the ability to drive vehicles and mechanisms has not been studied. During the period of drug treatment Nebivolol (if side effects occur), care should be taken when driving vehicles and mechanisms and when engaging in potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg.

14, 15, 20 or 30 tablets in a planar cell pack of film polyvinylchloride and aluminum foil.

14, 28 or 60 tablets in a can of high-density polyethylene.

1, 2 or 4 blisters 14 tablets 1, 2 or 4 blisters 15 tablets, 3 blisters with 20 tablets. 1 or 2 blisters of 30 tablets or one bank, along with instructions for medical use in a stack of cardboard.

Packaging:(14) - polyethylene cans (1) - packs of cardboard
(14) - packings, cellular, outline (1) - packs, cardboard
(14) - packings, cellular, outline (2) - packs, cardboard
(14) - packings cellular planimetric (4) - packs cardboard
(15) - packings, cellular, planimetric (1) - packs cardboard
(15) - packings, cellular, outline (2) - packs, cardboard
(15) - packings cellular planimetric (4) - packs cardboard
(20) - packings, cellular, outline (3) - packs, cardboard
(28) - polyethylene cans (1) - packs cardboard
(30) - packings cellular planimetric (1) - packs cardboard
(30) - packings cellular planimetric (2) - packs cardboard
(60) - polyethylene cans (1) - packs cardboard

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002902

Date of registration:12.03.2015 / 08.10.2015

Expiration Date:12.03.2020

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Nebivolol (Nebivolol)