Non-ticket - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate - 141.75 mg; starch corn - 46,00 mg; croscarmellose sodium - 13.80 mg; hypromellose (viscosity 15 mPa's) - 4.60 mg; polysorbate-80 - 0.46 mg; microcrystalline cellulose - 16,10 mg; silicon dioxide colloid - 0.69 mg; magnesium stearate 1.15 mg.

Description:

Round biconvex tablets of almost white color with cross-shaped notch for division.

Pharmacotherapeutic group:β1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Cardioselective β₁-adrenergic blocker. Nebivolol has antihypertensive, anti-anginal and antiarrhythmic effects. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively blocks postsynaptic β₁-adrenoceptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide (N0).

Nebivolol is a racemate of two enantiomers: SRRRNebivolol (D-nebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions:

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

- L- Nebivolol has a mild vasodilating effect due to modulation of the release of the vasodilating factor (NO) from the vascular endothelium. The hypotensive 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 hypotensive 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 slowing of atrioventricular conduction.

Pharmacokinetics:

Suction. After ingestion, there is a rapid absorption of both enantiomers. Eating does not affect absorption, therefore nebivolol can be taken regardless of food intake. Bioavailability of orally administered nebivolol and is an average of 12% in patients with "fast" metabolism (the effect of "first passage") and is almost complete - in patients with a "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%.

Excretion. Metabolized nebivolol by alicyclic and aromatic hydroxylation, partial N-dealkylation. The resulting hydroxy- and amino derivatives are conjugated with glucuronic acid and are derived as O- and N-glucuronides, kidneys (38%), through the intestine (48%). T_1/2 in patients with a "fast" metabolism: hydroxy metabolites - 24 h, enantiomers nebivolol - 10 h; in patients with a "slow" metabolism: hydroxymetabolites - 48 hours, enantiomers of nebivolol - 30-50 hours. Removal of unchanged nebivolol through the kidneys is less than 0.5 % from the dose of the drug taken orally.

Indications:

- Ahyperthermia;

- ischemic heart disease: prevention of angina pectoris attacks;

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

Contraindications:

- Hypersensitivity to the active substance or to one 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 Hg);

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

- atrioventricular blockade II and III degree (without artificial driver, rhythm);

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

- cardiogenic shock;

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

- metabolic acidosis;

- severe violations of liver function;

- bronchospasm and bronchial asthma in history;

- severe obliterating diseases of peripheral vessels ("intermittent" lameness, Raynaud's syndrome);

- myasthenia gravis;

- depression;

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

- age to 18 years (efficacy and safety in this age group are not studied).

Carefully:

- Renal failure;

- diabetes;

- hyperthyroidism;

- allergic diseases in history, psoriasis;

- chronic obstructive pulmonary disease;

- atrioventricular blockade of the 1st degree;

- angina of Prinzmetal;

- age over 75 years.

Pregnancy and lactation:

In pregnancy, the drug Nebilet® is prescribed only for vital indications, when the benefit to the mother exceeds the possible risk for. fetus or newborn (due to possible development in the fetus and newborn bradycardia, arterial hypotension, hypoglycemia). If treatment with Nebilet® is necessary, then you need to monitor the uteroplacental blood flow and fetal growth. Treatment should be interrupted for 48-72 hours before childbirth. In cases where this is not possible, it is necessary to establish strict observation of newborns within 48-72 hours after delivery.

Nebivolol is excreted in breast milk. If you need to take Nebilet® during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Nebilet® tablets are taken orally, once a day, preferably at the same time, regardless of food intake, with a sufficient amount of liquid.

Average daily, dose for treatment arterial hypertension and ischemic heart disease is 2.5-5 mg of the drug Nebilet® (1/2- 1 tab).

Nebilet® can be used in monotherapy or in combination with other means that reduce blood pressure.

In patients with renal insufficiency, as well as in patients older than 65 years the recommended initial dose is Yg tablets (2.5 mg) of Nebilet® per day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tablets of 5 mg at one time).

Treatment of chronic heart failure should start with a slow 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: while maintaining intervals of one to two weeks and focusing on the tolerance of this dose to the patient: a dose of 1.25 mg of Nebilet® (1/4 tablets of 5 mg) 1 time day, can be increased first to 2.5-5 mg once a day of Nebilet® (1/2 tablets of 5 mg or 1 tablet), and then - up to 10 mg (2 tablets of 5 mg) once a day.

The maximum daily dose is 10 mg once a day.

At the beginning of treatment and at each increase in the dose, the patient should be under the supervision of the doctor 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 worsening of the course of chronic heart failure). For division, place the tablet on a firm, level surface with a cross-shaped notch up, press the tablet with both index fingers (Figure 1). To obtain a quarter (1/4) of the tablet, repeat the same steps with half (1/2) tablets as shown in Fig.

Side effects:

Frequency of side effects: 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%), rarely (less than 0.01%), including individual reports.

Disturbances from the nervous system:

Often: headache, dizziness, fatigue, weakness, paresthesia;

Infrequently: depression, "nightmarish" dreams, confusion;

Rarely: fainting, hallucinations.

Disorders from the gastrointestinal tract:

Often: nausea, constipation, diarrhea;

Infrequently: dyspepsia, flatulence, vomiting.

Disorders from the cardiovascular system:

Infrequently: bradycardia, acute heart failure, atrioventricular blockade, orthostatic hypotension, Raynaud's syndrome.

Disturbances from the skin and subcutaneous tissues:

Infrequently: skin rash of erythematous nature, itching;

Rarely: aggravation of psoriasis;

In some cases: angioedema.

Other:

Infrequently: bronchospasm;

Rarely: dry eyes.

Overdose:

Symptoms: marked decrease in blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, atrioventricular (AV) blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest.

Treatment: washing the stomach, taking 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, with / injection of liquid and vasopressors. With bradycardia, it should be administered to / in 0.5 - 2 mg of atropine in the absence of a positive effect, the production of a transvenous or intracardiac electrostimulator is possible. When AV blockade (II-III st.) it is recommended to / in the introduction of β-adrenergic stimulants, if their ineffectiveness 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.With bronchospasm apply IV β₂-adrenoceptors. With ventricular extrasystole - lidocaine (do not administer antiarrhythmic drugs IA class).

Interaction:

Pharmacodynamic interaction

With simultaneous application β-adrenoconvertors 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 against the background of nebivolol.

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

With the simultaneous use of nebivolol with antiarrhythmic drugs of the first class and with amiodarone, an increase in the negative inotropic effect and prolongation of the excitation time at 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.

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

Pharmacokinetic interaction

With simultaneous application of nebivolol with drugs that inhibit the reuptake of serotonin, or by other means involving biotransformed isoenzyme CYP2D6, nebivolol increases the concentration in plasma, nebivolol metabolism slows down, which can lead to the risk of bradycardia.

When used simultaneously with digoxin, nebivolol no impact on the pharmacokinetic parameters of digoxin.

When applied simultaneously with nebivolol cimetidine, nebivolol plasma concentration increases.

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

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increase slightly, but this has no clinical significance.

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

Clinically significant interactions of nebivolol and warfarin have not been established. With the joint use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia) may be masked.

Special instructions:

Cancellation βadrenoblockers should be carried out gradually, within 10 days (up to 2 weeks in patients with ischemic 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. β-adrenoblockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 bpm. (see section "Contraindications").

When deciding whether to use Nebilet® in patients with psoriasis, the expected benefits of using the drug and the possible risk of exacerbation of psoriasis should be carefully correlated.

Patients using contact lenses should take into account that against the background of the use of β-adrenoblockers, the production of tear fluid can be reduced.

When conducting surgical interventions, an anesthesiologist should be warned that the patient is taking β-adrenoceptor blockers.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, caution should be exercised in the treatment of these patients, since Nebelet® can mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents for ingestion and insulin. Control the concentration of glucose in the blood plasma should be carried out 1 time in 4-5 months. (in patients with diabetes mellitus).

With hyperthyroidism, β-adrenoblockers can mask tachycardia. β-blockers should be used with caution in patients with chronic obstructive pulmonary disease, because it may worsen bronchospasm. β-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions.

Effect on the ability to drive transp. cf. and fur:The effect of Nebilet® on the ability to drive vehicles and control mechanisms has not been specifically studied.Studies of the pharmacodynamics of nebivolol have shown that the drug Nebilet® has no effect on the psychomotor function. During the period of treatment with Nebilet® (if side effects occur), care should be taken when driving vehicles and when engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 5 mg.

Packaging:

For 7 or 14 tablets in a planar cell package (blister) [PVC / aluminum foil].

For 1.2 or 4 blisters together with the Instruction for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011417 / 01

Date of registration:10.08.2009 / 02.04.2012

Expiration Date:Unlimited

The owner of the registration certificate:Berlin-Chemie / Menarini Pharma, GmbH Berlin-Chemie / Menarini Pharma, GmbH Germany

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp18.06.2018

Illustrated instructions

Instructions

Nebilet® (Nebilet®)