Nebivolol Canon - instructions for use, dose, side effects, contraindications

active substance: nebivolol hydrochloride 5.45 mg, calculated as nebivolol 5 mg; Excipients: giprolase (hydroxypropyl cellulose) 5 mg, calcium hydrogen phosphate dihydrate 55.5 mg, silicon dioxide colloid (Aerosil) 0.7 mg, croscarmellose sodium (impellose) 3 mg, lactose monohydrate (sugar milk) 33.75 mg, vegetable hydrogenated oil 0, 6 mg, microcrystalline cellulose 35 mg, magnesium stearate 1 mg.

Description:Tablets are white or almost white, biconvex, with a cruciform risk.

Pharmacotherapeutic group:beta1-blocker selective.

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a lipophilic, cardioselective beta-adrenoblocker 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: SRRR- nebivolol (Dnebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions:

- D- Nebivolol is a competitive and highly selective blocker of beta1-adrenoreceptors (affinity for beta 1-adrenergic receptors is 293 times higher than for beta2-adrenergic receptors).

- LNebivolol has a vasodilating effect due to 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 (HR) at rest and during physical activity, reduces the end-diastolic pressure of the left ventricle, reduces the overall peripheral vascular resistance, improves diastolic function of the heart (reduces filling pressure), increases the ejection fraction, reduces the mass of the myocardium and the myocardial mass index.

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 is due to the suppression of the automaticity of the heart (including in the pathological focus) and the slowing of the 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 L- nebivolol - 97.9%.

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, 38% (the amount of unchanged active substance is less than 0.5%) is given 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 Tug 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 (CHD): 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);

- 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 section "Interaction 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.

There is no data on the isolation of nebivolol in breast milk. Therefore, taking Nebivolol Canon is not recommended for women during lactation. If Nebivolol Canon is used during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

The drug Nebivolol Canon should be taken inside at the same time, regardless of food intake, without chewing and drinking with a sufficient amount of liquid.

Arterial hypertension and ischemic disease of the sickle

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 two-week intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg Nebivolol Canon (1/4 tablets 5 mg) once a day,can be increased first to 2.5 - 5 mg of Nebivolol Canon (1/2 tablets of 5 mg - 1 tablet), and then 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 Nebivolol Canon once a day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.

During the titration phase, in case the current worsening of chronic heart failure or intolerance to the drug is recommended to reduce the dose of the drug Nebivolol Canon or, if necessary, immediately stop taking it (in the case of pronounced hypotension, worsening of heart failure flow with acute pulmonary edema, in the case 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, "nightmarish" dream, hallucination.

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, shortness of breath, heart rhythm disturbances, Raynaud's syndrome, peripheral edema, cardialgia, worsening of CHF flow¹.

Allergic reactions from the skin: skin itch, eruptive rash.

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.

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, with / injection of liquid and vasopressors.

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 (P-S st.) is recommended iv administration of beta-adrenomimetics, if they are ineffective, consider setting up 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-adrenomimetiki.

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

Interaction:

Floktaphenin: in the case of shock or arterial hypotension caused by floktaphenin, beta-adrenoblockers weaken the 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).

With simultaneous use with antiarrhythmic agents of the first class and with amiodarone, an increase in the negative inotropic effect and an extension of the time of excitation to the atria are possible.

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 (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.

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 beats / min, with a load - no more than 110 beats / minute.

Beta-adrenoblockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats / min (see Contraindications section).

When deciding whether to use Nebivolol Canon, patients with psoriasis should carefully correlate the perceived benefits of the drug and 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 conducting surgical interventions, an anesthesiologist should be warned that the patient is taking nebivolol.

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 (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 thyroid 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.

By 7, 10 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 1, 2, 4, 8 contour cell packs of 7 tablets or 1, 2, 3, 6 contiguous cell packs of 10 tablets or 1, 2 circuit cell packs of 30 tablets together with instructions for use are placed in a pack of cardboard .

Packaging:(10) - contour cell packaging / Contouring package, instructions for medical use of the drug /
(14) - Contour-cell packaging / Contour-cell packaging, instructions for medical use of the drug /
(20) - contour cell packaging / Contouring package, instructions for medical use of the drug /
(28) - Contour-cell packaging / Contour-cell packaging, instructions for medical use of the drug /
(30) - contour cell packaging / Contouring package, instructions for medical use of the drug /
(56) - Contour-cell packaging / Contour-cell packaging, instructions for medical use of the drug /
(60) - Contour-cell packaging / Contour-cell packaging, instructions for medical use of the drug /
(7) - Contour-cell packaging / Contour-cell packaging, instructions for medical use of the drug /

Storage conditions:

In a dry, protected from light 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-001172

Date of registration:11.11.2011

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Nebivolol Canon (NEBIVOLOL CANON)