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

Excipients: silicon dioxide colloid 0.65 mg, magnesium stearate 2.00 mg, croscarmellose sodium 11.5 mg, macrogol 6000 20.0 mg, lactose monohydrate 192.4 mg.

Description:

Round tablets of white color on one side are convex (with marking “N 5 "), on the other - with a cross-shaped risk with a towering edge on each of the divided sectors.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a lipophilic, cardioselective beta1 -adrenergic blocker of the third generation with vasodilating properties. Has antihypertensive, anti-anginal and antiarrhythmic effect. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively blocks synaptic and postsynaptic beta 1-adrenergic receptors, 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 (D- nebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions: D- Nebivolol is a competitive and highly selective blocker of beta adrenoreceptors (affinity for betai-adrenoceptors 293 times higher than to beta-adrenoreceptors).

- L- Nebivolol has a mild vasodilating effect due to the modulation of the release of the relaxing factor (N0) from the vascular endothelium.

The hypotensive effect develops on the 2nd-5th day of treatment, stable effect is observed after 1 month. This effect persists with long-term treatment.

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

The use of nebivolol improves the indices of systemic and intracardiac hemodynamics. Nebivolol reduces heart rate and heart rate at rest and under physical exertion, reduces the end-diastolic pressure of the left ventricle, reduces the overall peripheral vascular resistance, improves the diastolic function of the heart (reduces filling pressure), increases the ejection fraction.

Reducing the need for myocardium in oxygen (decreasing heart rate, reducing preload and afterload), reduces the number and severity of angina attacks and improves the tolerance of exercise.

Antiarrhythmic effect due to suppression automaticity of the heart (including in the pathological focus) and slowing of atrioventricular (AV) conductivity.

Pharmacokinetics:

After oral administration nebivolol quickly absorbed from the gastrointestinal tract. Eating does not affect suction, so nebivolol can be taken regardless of food intake.

Bioavailability averages 12% in patients with "fast" metabolism and is almost complete in patients with "slow" metabolism. The effectiveness of nebivolol does not depend on the metabolic rate.

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%, and for L97.9% of nebivolol.

Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the isoenzyme CYP2D6.

After the administration of 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 values of the half-life (T1/2) enantiomers of nebivolol from the blood plasma averagely 10 hours. In patients with a "slow" metabolism, these values increase 3-5 times.

In patients with "fast" metabolism, the T1 / 2 hydroxymetabolites of both enantiomers from blood plasma averagely 24 hours, in patients with a "slow" metabolism these values are approximately 2-fold increased.

The pharmacokinetics of nebivolol is not affected by age and sex of patients.

Indications:

- arterial hypertension;

- ischemic heart disease (IHD): prevention of attacks of stable angina pectoris;

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

Contraindications:

- increased sensitivity to nebivolol or one of the components of the drug;

- severe liver dysfunction;

- acute heart failure;

- cardiogenic shock;

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

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

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

- bronchospasm and bronchial asthma;

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

- depression;

- metabolic acidosis;

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

- severe arterial hypotension;

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

- age to 18 years;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

- simultaneous administration with floktaphenin, sultopride (see Interactions with other drugs);

Carefully:

Carefully should apply the drug with severe renal failure (creatinine clearance (CC) less than 20 ml / min),liver function abnormalities, diabetes mellitus, hyperthyroidism, desensitizing therapy, psoriasis, grade I atrioventricular block, prinzmetal angina, chronic obstructive pulmonary disease (COPD), and elderly patients (over 65 years of age).

Pregnancy and lactation:

In pregnancy, the drug is prescribed only on strict indications, when the benefit to the mother exceeds the risk for the fetus (in connection with the possible development of a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory paralysis). Treatment should be interrupted for 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict observation of the newborn within 48-72 hours after delivery.

Studies in animals have shown that nebivolol excreted in breast milk. There is no data on the isolation of nebivolol in breast milk. Therefore, taking Nevotenz is not recommended for women during lactation. If the use of the drug Nevotenz during lactation is necessary, then breastfeeding should be discontinued.

Dosing and Administration:

Nevotenz should be taken inside at the same time of the day, regardless of food intake,not liquid and squeezed with enough liquid.

Arterial hypertension and ischemic heart disease

The average daily dose for the treatment of hypertension and IHD 5 mg (1 tablet) 1 time per day. The optimal effect becomes pronounced after 1-2 weeks of treatment, and in some cases - after 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 10 mg (2 tablets of 5 mg at a time). The maximum daily dose is 10 mg.

In patients with renal insufficiency, as well as in patients older than 65 years the initial dose is 2.5 mg / day (1/2 tablet of 5 mg). If necessary, increase the dose to 5 mg.

At the expressed infringements of function of kidneys (KK less than 20 ml / mines) and at patients with serious diseases of a liver the maximum daily dose makes 10 mg.

Increasing the dose in these patients should be done with extreme caution.

Chronic heart failure

Treatment of chronic heart failure 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 according to the following scheme, maintaining weekly intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg of Nevotenz (1/4 tablets of 5 mg) once a day can be increased first to 2,5 - 5 mg of the drug Nevotenz (1/2 tablets of 5 mg - 1 tablet), and then - up to 10 mg (2 tablets of 5 mg) once a day. The patient should be under the supervision of a doctor within 2 hours after taking the first dose of the drug, and also after each subsequent increase in the dose. Each dose increase should be carried out not later than 2 weeks. The maximum recommended dose for CHF therapy is 10 mg of Nevotenz once a day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.

During the titration phase, in case of worsening of the course of chronic heart failure or intolerance of the drug, it is recommended to reduce the dose of Nevotenz or, if necessary, to stop it immediately (in case of pronounced arterial hypotension, deterioration of the course of CHF with acute pulmonary edema, in case of development of cardiogenic shock, symptomatic bradycardia or AV blockade).

Side effects:

From the central nervous system: headache, dizziness, fatigue, paresthesia, depression, decreased ability to concentrate, drowsiness, insomnia, nightmares, hallucinations, loss of consciousness.

From the digestive system: nausea, constipation, flatulence, diarrhea, dryness of the oral mucosa.

From the side of the cardiovascular system: bradycardia, heart failure, AV blockade, orthostatic hypotension, peripheral circulatory disorders (cold sensation in the extremities, cyanosis), shortness of breath, heart rhythm disturbances, Raynaud's syndrome, peripheral edema, cardialgia, worsening of CHF flow¹, marked decrease in blood pressure. Allergic reactions from the skin: skin itching, erythematous rash, angioedema, hyperemia of the skin, alopecia.

From the respiratory system: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis), bronchospasm in patients with bronchial asthma or airway obstruction in history, rhinitis.

Other: photodermatosis, hyperhidrosis, exacerbation of psoriasis, visual impairment (dry eyes), a violation of potency.

1 - This side effect predominantly occurs during the titration of the drug dose.

Overdose:

Symptoms: the expressed depression of a BP, the expressed bradycardia, AV blockade, cardiogenic shock, acute heart failure, cardiac arrest, bronchospasm, loss of consciousness, coma, nausea, vomiting, cyanosis.

Treatment: gastric lavage, reception of activated carbon. 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, in / in the administration of liquid and vasopressors; as a follow-up, it is possible to administer 1-10 mg of glucagon.

With severe bradycardia, intravenous infusion of 0.5-2 mg of atropine is administered, in the absence of a positive effect, a transvenous artificial pacemaker is available.

When AV blockade (H-S st.) It is recommended intravenous injection of beta-adrenomimetics, 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 enter intravenously beta2-adrenomimetics.

With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class).

With convulsions - intravenously diazepam.

Interaction:

Floktaphenin: in the case of shock or hypotension caused by reception floctafenine, beta-blockers attenuate compensatory mechanisms of the cardiovascular system. Sulphoprid: increased risk of ventricular arrhythmia, especially as a "pirouette" (torsade des pointes).

With simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) the negative effect on myocardial contractility and AV conductivity. Contraindicated in / in the administration of verapamil on the background of nebivolol. When combined with antihypertensive drugs, nitroglycerin or BCCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin).

When used simultaneously with antiarrhythmic drugs, Class I and amiodarone, it is possible to increase the negative inotropic effect and prolong the time of excitation in the atria.

With the simultaneous use of nebivolol with cardiac glycosides, no increase in the effect on slowing AV conductivity.

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 (NSAIDs) have not been established. Acetylsalicylic acid as an antiplatelet agent can be used concomitantly with nebivolol.

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

Pharmacokinetic interaction

When used simultaneously with drugs that inhibit serotonin reuptake, or other means, biotransforming with the participation of isoenzyme CYP2D6, the metabolism of nebivolol slows down.

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 (data on the effect on the pharmacological effects of the drugare absent). The simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increased slightly, but this has no clinical significance. Simultaneous administration of ethanol, furosemide or hydrochlorothiazide did not affect the pharmacokinetics of nebivolol.

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

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

Special instructions:

The abolition of beta-adrenoblockers 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.

Beta-adrenoblockers 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 appointment of the drug Nevotenz, patients with psoriasis should carefully correlate the intended use of the drug and the possible risk of exacerbation of the course of psoriasis.

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

When conducting surgical interventions, the anesthetist should be warned that the patient is taking Nevotenz.

Nevotenz does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, care should be taken in the treatment of these patients, because Nevotenz may mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents.

Control of the concentration of glucose in the blood plasma should be done 1 time in 4-5 months. (in patients with diabetes mellitus). Beta-adrenoblockers should be used with caution in patients with COPD, as bronchospasm may worsen. With hyperfunction of the nasal gland, the drug levels tachycardia.

Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions. The effectiveness of beta-blockers in smokers is lower than in non-smoking patients.

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

Research work has shown that nebivolol does not affect the speed of psychomotor reactions. Pilots flying crew with arterial hypertension I degree (admitted to flight work), the drug is prescribed in an initial dose of 2.5 mg. In the future (no earlier than 2 weeks) with good tolerability of treatment and insufficient control of blood pressure, a 2.5 mg dose increase is possible. The recommended dose is 5 mg / day. Some patients may experience side effects, most often dizziness, due to lowered blood pressure. If such effects occur, the patient should not drive vehicles or engage in potentially hazardous activities requiring special attention and speed of psychomotor reactions. These effects occur most often immediately after the start of treatment or with increasing doses.

Form release / dosage:

Tablets 5 mg.

For 7 or 10 tablets in Al / PVC blisters. For 1, 2, 4, 8 blisters for 7 tablets or 1, 3, 5 blisters of 10 tablets per cardboard pack together with instructions for use.

Packaging:(10) - blisters (1) - packs of cardboard
(10) - blisters (10) - packs of cardboard
(10) - blisters (3) - packs cardboard
(10) - blisters (5) - packs of cardboard
(7) - blisters (1) - packs cardboard
(7) - blisters (2) - packs cardboard
(7) - blisters (4) - packs cardboard
(7) - blisters (8) - packs cardboard

Storage conditions:

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-000016

Date of registration:25.10.2010

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

ACTAVIS, Ltd. Iceland

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp02.08.2015

Illustrated instructions

Instructions

Non-attendance (Nevotens)