Nebilong - instructions for use, dose, side effects, contraindications

Excipients: lactose, microcrystalline cellulose, betadix, docusate sodium, croscarmellose sodium, novidone, silicon dioxide colloid, talc, magnesium stearate.

Description:

Tablets 2.5 mg: flat round tablets of white or almost white color with a facet with a risk on one side

Tablets 5.0 mg: flat round tablets of white or almost white color with a facet with a risk on one side

Tablets 10.0 mg: nround white tablets white or almost white with a chamfer with a risk on one side

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:Nebivolol is a lipophilic, cardioselective beta-adrenoblocker with vasodilating properties. Has antihypertensives, antiangiagnosis and antiarrhythmic effect.Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively blocks synaptic and postsynaptic betagadrenoreceptors, making them inaccessible to' catecholamine, 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:

- DNebivolol is a competitive and highly selective betag blocker

adrenergic receptors (affinity for beta1-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.

Antihypertensive effect develops on the 2nd-5th day of treatment, stable effect is observed after 1 month. This effect persists with long-term treatment. Antihypertensive effect is also due to a decrease in the activity of the renin-angiotensin-aldosterone system (does not directly correlate with changes in renin activity in blood plasma).

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

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

Antiarrhythmic "action is caused by suppression of pathological automatism of the heart (including in the pathological focus) and slowing down atrioventricular (AV) conduction.

Pharmacokinetics:

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

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 the blood plasma of 1-30 μg / l are proportional to the dose.

Connection with blood plasma proteins (mainly with albumin) for Dnebivolol is 98.1%, and for K-nebivolol - 97.9%.

Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites. Metabolized nebivolol by alicyclic and aromatic hydroxylation, partial N-dealkylation. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the isoenzyme CYP2D6. - After the introduction 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 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 values of the hydroxymetabolites of both enantiomers from plasma are on average 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;

- cardiac ischemia: prevention of attacks stable

angina pectoris;

- chronic heart failure (in combination therapy).

Contraindications:

- hypersensitivity to the active substance or one of the components of the drug and to other beta-blockers;

- severe violations of liver function;

- 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 an artificial pacemaker);

- broncho-obstructive syndrome in chronic obstructive pulmonary disease and bronchial asthma; severe forms of bronchial asthma and chronic obstructive pulmonary disease in the anamnesis;

- pheochromocytoma (without simultaneous application of alpha-adrenocortical blockers);

- depression;

- metabolic acidosis;

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

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

- severe peripheral atherosclerosis;

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

- lactose intolerance, lactase deficiency or pokozo-galactose malosorption (the preparation contains lactose);

- simultaneous, reception with floktaphenin, sultopride (see section Interaction with other medicinal products);

Carefully:liver failure, diabetes mellitus, hyperthyroidism, episodes of bronchospasm in the anamnesis, allergic diseases in the anamnesis (it is possible to increase sensitivity to allergens, weight allergic reactions, decrease the response to adrenaline), psoriasis,atrioventricular blockade of the 1st degree, angina of Prinzmetal; chronic obstructive pulmonary disease (COPD), age (over 65 years), peripheral atherosclerosis.

Pregnancy and lactation:

In pregnancy, Nebilong is prescribed only for vital signs, when the benefit to the mother exceeds the risk to the fetus (due to the possible development of a bodycardia in the newborn, 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 Nebilong is not recommended for women during the feeding period. If the use of Nebilong during lactation is necessary, then breastfeeding should be discontinued.

Dosing and Administration:

Nebilong should be taken orally, once a day, preferably at the same time, regardless of the intake of the food without chewing and drinking with a sufficient amount of liquid.

Arterial hypertension

The average daily dose for the treatment of hypertension is 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, daily, the dose can be increased to 10 mg. 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. If necessary, increase the dose to 5 mg.

In severe violations of kidney function (KC less than 20 ml / min) and in patients with liver disease, the maximum daily dose is 10 mg.

Increasing the dose in these patients should be done with extreme caution. Chronic heart failure (CHF).

Treatment of chronic heart failure should begin with a gradual increase in the dose before, achieving an individual, optimal maintenance DOSES.

Selection of the dose at the beginning of treatment should be carried out according to the following scheme, while maintaining intervals of up to two weeks and based on the tolerance of this dose to the patient: a dose of 1.25 mg (1/2 tablets of 2.5 mg) once a day can be first increased to 2.5-5 mg once-every day of the Nebilong drug, and then to 10 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, as well as 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 Nebilong Graz per day. During the titration regular monitoring of blood pressure, heart rate and symptoms is recommendedthe severity of CHF.

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

Side effects:

The frequency of side effects is presented in the following gradation: Often (more 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.Impaired nervous system:

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

Infrequently: depression, bright dreams, confusion, insomnia;

Rarely: syncope, hallucinations, amnesia.

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, 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.

Disturbances from the skin and subcutaneous tissues:

Infrequently: skin rash of erythematous nature, itchy skin, hyperemia of the skin;

Rarely: aggravation of psoriasis, alopecia;

In some cases: angioedema.

From the respiratory system:

Infrequently: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis), and bronchoospasm in patients with bronchial asthma. asthma or an airway obstruction in an anamnesis.

Other: photodermatosis, hyperhidrosis, visual impairment (dry eyes), sexual dysfunction.

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

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, severe disorders intracardiac conduction, shock, asystole, respiratory arrest, bronchospasm, loss of consciousness, convulsions, coma, nausea, vomiting, cyanosis, hypoglycemia, hyperkalemia.

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 / in the administration of liquid and vasopressors.

With bradycardia, I / O is injected with 0.5-2 mg of atropine, in the absence of a positive effect, a transvenous or intracardiac artificial pacemaker is available.

When AV blockade (II-III st.) is recommended intravenously for the introduction of beta-adrenomimetics, if they are ineffective, consider 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. When bronhospazme enter intravenously beta2-adrenomimetics. With convulsions - intravenous diazepam.

With ventricular ekstrasistolii-lidocaine (you can not inject antiarrhythmics IA class).

Interaction:

Floktaphenin: in case of shock or arterial hypotension; induced by floktaphenin, beta-adrenoblockers weaken the compensatory mechanisms of the cardiovascular system.

Sulphoprid; increased risk of ventricular arrhythmia, especially as pirouette.

With the simultaneous use of beta-blockers with blockers "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). In an application with aitiaritmicheskymi means increased risk cardiodepressive bradycardia activities and in combination with any antiarrhythmic, means. With .amiodarone also increases the risk of atrioventricular blockade. The risk of ventricular arrhythmia, called sotalol, amiodarone increases, dronedarone, quinidine and prokainamidoi (avoid sharing application).

With simultaneous applicationnebivolol, 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 development of arterial hypotension.

Clinically significant interaction of nebivolol and non-steroidal anti-inflammatory drugs (NSAIDs) is not established. Acetylsalicylic acid as an antiplatelet agent can be used concurrently with / nebivolol.

Glucocorticosteroids and estrogens,gestagens weaken the anti-hypersensitivity effect of beta-blockers.

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

Allergens used for immunotherapy or extracts of allergens for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving nebivolol.

Iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.

Pharmacokinetic interaction.

When used simultaneously with drugs that inhibit serotonin reuptake, or, by other means, biotransforming with the participation of isoenzyme CYP2D6, the metabolism of nebivolol / slows down, which can lead to a risk of bradycardia.

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

With simultaneous applications 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 the concentration of active substances in the blood plasma increased slightly, but this is not of clinical significance.

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

There is no clinically significant interaction between nebivolol and warfarin.

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

When combined with nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia, tremor) can be masked.

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 selected 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.

When deciding whether to use Nebilong, patients with psoriasis should carefully correlate the expected 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 performing surgical interventions, the surgeon / anesthesiologist should be alerted that the patient is receiving Nebilong.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus.However, caution should be exercised in the treatment of these patients, since Nebilong 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 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:During the treatment period it is necessary to observe, caution when driving vehicles and engage in other potentially dangerous activities that require increased concentration of attention and quickness of psychomotor reactions.

Form release / dosage:

Tablets of 2.5 mg; 5.0 mg or 10.0 mg.

For 10 tablets in A1 / A1 blister. For 1, 3 or 5 blisters together with the instructions, but use in a cardboard box.

Packaging:(15) - Blister Aluminum / Pvc.(1) - Cardboard tutu.
(15) - Blister Aluminum / Pvc. (4) - Cardboard tutu.
(15) - Blister Aluminum / Pvc. (7) - Cardboard tutu.

Storage conditions:

In a dry, 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 the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000597

Date of registration:21.09.2011

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspMICRO LABS LIMITED MICRO LABS LIMITED India

Information update date: & nbsp02.07.2015

Illustrated instructions

Instructions

Niebelong (Nebilong)