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

Excipients: lactose monohydrate 92.28 mg, starch corn 45.00 mg, croscarmellose sodium 10.00 mg, cellulose microcrystalline 23.67 mg, magnesium stearate 1.00 mg, silicon dioxide colloid 0.60 mg, povidone 2.00 mg.

Description:Round flat white tablets with a risk on one side.

Pharmacotherapeutic group:beta 1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a cardioselective beta-adrenoblocker of the third generation with vasodilating properties. It has anti-hypertensive, anti-anginal and antiarrhythmic effects. It reduces the heart rate (HR) and lowers blood pressure (BP) at rest and during physical activity, reduces the end-diastolic pressure of the left ventricle, reduces the overall peripheral vascular resistance, improves the diastolic function of the heart (reduces the final diastolic filling pressure of the left ventricle), increases the fraction ejection.

Competitively and selectively blocks postsynaptic β-adrenergic receptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide (N0). Iebivolol is a racemate of two enantiomers: SRRR- nebivolol (D-nebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions:

- D- Nebivolol is a competitive and highly selective blocker of [β1-adrenergic receptors;

- LNebivolol has a vasodilating effect due to the modulation of the release of the vasodilating factor (N0) from the vascular endothelium. Antihypertensive effect is also due to a decrease in the activity of the renin-angiotensia-aldosterone system (RAAS) (does not directly correlate with changes in renin activity in blood plasma).

A stable antihypertensive 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), iebivolol reduces the number and severity of angina attacks and increases the tolerance of exercise.Anhyarrhythmic action is caused by suppression of pathological automatism of the heart (including in the pathological focus) and slowing of atrioventricular conduction.

Pharmacokinetics:

Suction

After ingestion, iebivolol is rapidly absorbed from the gastrointestinal tract (GIT). Food intake nc has an effect on absorption, therefore, ebivolol can be taken regardless of the time of ingestion. Bioavailability of ingested nebivolol averages 12% in patients with "fast" metabolism (the effect of "primary transmission") and is almost complete in patients with "slow" metabolism. Distribution

Binding to blood plasma proteins (mainly associated with albumin) for DThe nebivolol is 98.1%, for L- nebivolol - 97.9%. Metabolism

Metabolized iebivolol with the formation of active metabolites, by alicyclic and aromatic hydroxylation, partial N- dealkylation.

The resulting hydroxy- and amino-derivatives are conjugated to piocuronic acid and are derived as O- and N-glucuronides.

The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on isoenzyme CYP2D6. The rate of nc metabolism affects the effectiveness of nebivolol.

Given the differences in metabolic rate, the dose of the drug should always be selected individually - patients with slow metabolism require a smaller dose.

Excretion

One week after taking 38% of the total dose, nebivolol is excreted by the kidneys (the amount of unchanged nebivolol is less than 0.5% of the dose) and 48% through the intestine. Half-life (T1 / 2) in patients with "fast" metabolism: hydroxy metabolites - 24 h, enantiomers of nebivolol - 10 h; in patients with a "slow" metabolism, the half-life increases by 2-5 times, amounting to 48 hours for hydroxymetabolites, and for enantiomers of nebivolol 30-50 hours.

The patient's age does not affect the pharmacokinetics of the drug.

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;

- severe hepatic impairment (Child-Pugh class C);

- acute heart failure, cardiogenic shock;

- chronic heart failure in the stage of decompensation (requiring intravenous administration of drugs with inotropic effect);

- syndrome of weakness of the sinus node, including sinoatrial block; atrioventricular blockade of II and III degree (without artificial pacemaker);

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

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

- severe violations peripheral blood circulation ("intermittent" limp, Raynaud's syndrome);

- bronchospasm and bronchial asthma in history;

- pheochromocytoma (without simultaneous application of alpha-adrnosblokatorov);

- metabolic acidosis;

- severe renal dysfunction (creatinine clearance less than 20 ml / min);

- myasthenia gravis;

- depression;

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

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

- The simultaneous administration of floktaphenin, sultopride (see section "Interaction with other drugs"

- Lactation period

Carefully:

- renal failure (creatinine clearance more than 20 ml / min);

- diabetes;

- hyperthyroidism;

- allergic diseases in history, psoriasis;

- chronic obstructive pulmonary disease;

- atrioventricular blockade of the 1st degree;

- angina of Prinzmetal;

- use in elderly patients (over 65 years);

- pregnancy.

Pregnancy and lactation:

In pregnancy, NEBIVOLOL-NANOLEC is prescribed only for vital indications, when the benefit to the mother exceeds the possible risk to the fetus or newborn (due to the possibility of delayed fetal growth, fetal death, premature birth, and fetal and newborn bradycardia, arterial hypotension , hypoglycemia). If treatment with NEBILOL-NANOLEC is necessary, then it is necessary to monitor utero-placental blood flow and fetal growth, and if unwanted effects on the course of pregnancy and fetal conditions occur, treatment with NEBIVOL-NANOLEC should be discontinued.

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 the first 3 days after delivery (hypoglycemia and bradycardia may occur).

Studies in animals have shown that nebivolol excreted in breast milk. If the use of the drug NEBIVOLOL-NANOLEK during lactation is necessary, breastfeeding should be discontinued.

Dosing and Administration:

Nebivolol-Nanolek tablets are taken orally, once a day, preferably at the same time, regardless of the time of ingestion, without chewing and washing down with a sufficient amount of liquid (approximately 1 cup).

Arterial hypertension and coronary heart disease (IHE)

Average daily dose for treatment arterial hypertension and CHD is 2.5-5 mg of the drug NEBIVOLOL-NANOLEK (1/2 tablets of 5 mg - 1 tablet of 5 mg) once a day. Clinically significant effect appears after 1-2 weeks of treatment, and in some cases - after 4 weeks. NEBIVOLOL-NANOLEC can be used in monotherapy or in combination with other means that reduce blood pressure.

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

Patients with renal insufficiency (creatinine clearance more than 20 ml / min): the recommended initial dose is 2.5 mg per day (1/2 tablet 5 mg each) of the drug NEBIVOLOL-NANOLEC. If necessary, the daily dose can be increased to 5 mg (1 tablet).

Patients of advanced age (over 65 years): the recommended initial dose is 2.5 mg per day (1/2 tablets of 5 mg) of the drug NEBIVOLOL-NANOLEC per day. If necessary, the daily dose can be increased to 5 mg (1 tablet). However, given the limited experience of using nebivolol drugs in elderly patients (over 65 years of age), care must be taken to ensure that patients are closely monitored.

Cronical heart failure

Treatment of chronic heart failure should begin with a slow increase in the dose until an individual optimal maintenance dose is achieved.

Prescribe NEBIVOLOL-NANOLECE is available to patients with stable chronic heart failure who did not experience acute heart failure within the last 6 weeks.

In patients receiving cardiovascular drug therapy, including diuretics and / or digoxin and / or angiotensin-converting enzyme (ACE) inhibitors and / or angiotensin II receptor antagonists, doses of the drugs should be stabilized 2 weeks before treatment with NEBIVOLOL-NANOLECE.

Begin the treatment of chronic heart failure by beta-adrenergic blockers with a clinically stable patient for the past 2 weeks. Selection of the dose at the beginning of therapy should be carried out according to the following scheme, maintaining the 2-week intervals: the initial dose, which is 1.25 mg once a day (in this scheme, you need to use other drugs with MNI: nebivolol in tablets of 2.5 mg or 5 mg with a cross-like risk) may be increased first to 2.5 mg (1/2 tablets 5 mg) once a day, then to 5-10 mg of the drug NEBIVOLOL-NANOLEC (1-2 tablets of 5 mg) once a day.

Each dose increase should be carried out not later than 2 weeks, depending on the individual tolerability of the drug. The maximum daily dose for the treatment of chronic heart failure is 10 mg 1 time per day.

At the beginning of treatment and at each dose increase, the patient should be under the supervision of the doctor for at least 2 hours to ensure that the clinical condition remains stable (especially: blood pressure, heart rate, conduction disorders, and symptoms of worsening of the course of chronic heart failure).

If during the selection of the dose the chronic heart failure worsens or if the drug becomes intolerant, it is recommended to reduce the dose of the drug or, if necessary, stop taking it immediately (in case of severe arterial hypotension, worsening of chronic cardiac insufficiency with acute pulmonary edema, in case of development of cardiogenic shock, symptomatic bradycardia or atrioventricular blockade). Treatment of stable chronic heart failure with NEBIVOLOL-NANOLEC is usually prolonged.

Treatment with NEBILOL-NANOLEC is not recommended to stop abruptly (if it is not necessary), as this can lead to a temporary worsening of the course of heart failure. When The dose should be reduced gradually, half every week.

Patients with renal insufficiency:

With mild and moderate renal failure (creatinine clearance more than 20 ml / min) there is no need to adjust the dose. It is necessary to select the dose individually, gradually increasing to the maximum tolerable.There is no experience with nebivolol in patients with severe renal dysfunction (creatinine clearance less than 20 ml / min), so it is not recommended in such patients (see "Contraindications").

Older patients:

There is no need to adjust the dose, so it is necessary to select the dose individually, gradually increasing to the maximum tolerable.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development in the following way:

Often - not less than 10%; often - ns less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; rarely (including isolated cases) - less than 0.01%, frequency unknown - according to available data to estimate the frequency of development is impossible.

Sign "*" highlighted the undesirable phenomena that were noted in the therapy of chronic heart failure.

From the immune system:

Frequency unknown: angioedema, hypersensitivity. Disorders from the central nervous system:

Often: dizziness*;

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

Infrequently: depression, "nightmarish" dreams, confusion;

Rarely: fainting, hallucinations.

Disorders from the side of the organ of vision:

Infrequently: impaired vision;

Rarely: dryness of the mucous membrane of the eye.

Disorders from the cardiovascular system:

Very often: bradycardia *.

Often: aggravation of chronic heart failure*, orthostatic hypotension* atrioventricular block of degree I*, peripheral edema;

Infrequently: bradycardia, acute heart failure, slowing of atrioventricular conduction / atrioventricular blockade, orthostatic hypotension, Raynaud's syndrome, aggravation of "intermittent" lameness.

Disturbances from the respiratory system:

Often: dyspnea;

Infrequently: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis).

Disorders from the gastrointestinal tract:

Often: nausea, constipation, diarrhea;

Infrequently: dyspepsia, flatulence, vomiting.

Disturbances from the skin and subcutaneous tissues:

Infrequently: skin itching, erythematous rash, photodermatosis, hyperhidrosis; Rarely: aggravation of psoriasis;

Frequency unknown: alopecia.

On the part of the reproductive system:

Infrequently: erectile disfunction.

General disorders and disorders at the site of administration:

Often: drug intolerance *:

Rarelychill / cyanosis of the extremities.

With the use of certain beta-adrenergic receptor antagonists, the following undesirable reactions have also been described: psychosis, cold / cyanosis of the extremities.

Overdose:

Symptoms: acute heart failure, marked decrease in blood pressure, nausea, vomiting, cyanosis, severe bradycardia, atrioventricular (AV) blockade, brachospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest.

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 intravenous fluid and vasopressors, intravenous glucagon (50-100 μg / kg body weight) may be taken as a follow-up. With bradycardia, 0.5-2 mg of atropine should be administered intravenously, in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be inserted. When AV blockade (II-III century), intravenous administration of beta-adrenomimetics is recommended, 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, dopamine, dobutamine (starting at a dose of 2.5 μg / min) or vasodilators is advisable. When bronchosnazm use intravenous beta2-adrenomimetikn. With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class). With convulsions - intravenously diazepam. When hypoglycemia is recommended intravenous injection of a solution of dextrose (glucose).

Interaction:

Pharmacodynamic interaction

It is contraindicated to prescribe concurrently with nebivolol the following medicines:

- Floktaphenin: there is a threat of developing arterial hypotension or shock.

- Sul- tonrida: an increased risk of ventricular arrhythmia, especially as a "pirouette" (torsade des pointes).

At simultaneous application of β-adrenoblockers with blockers of "slow" calcium channels (BCCC) (verapamil and diltiazem) the negative effect on myocardial contractility and AV conductivity. Contraindicated in / in the administration of verapamil against the background of nebivolol.

Simultaneous use of nebivolol with BCCC dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, Nicardine, nimodipine, nitrendipine) may increase the risk of 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 nebivolol is combined with antihypertensive drugs, nitroglycerin can develop severe arterial hypotension (special caution is necessary when combined with prazosin).

With the simultaneous use of nebivolol with antihypertensive drugs of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of heart failure due to a decrease in sympathetic tone (decrease in heart rate and cardiac output, symptoms of vasodilation). In the case of a sharp cancellation of these drugs, especially before the abolition of piebifolium, it is possible to develop a "ricochet" arterial hypertension.

With simultaneous use of piebifol with antiarrhythmic drugs of class I (chinidia, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone) and with amiodaroma, an increase in the negative iotropic effect and an extension of the time of excitation through the atrioventricular node are possible. The simultaneous use of peybivolol with cardiac glycosides can cause a slowdown of atrioventricular conduction.

Simultaneous use of piebifolium and drugs for general anesthesia can cause suppression of reflex tachycardia and increase the risk of developing arterial hypotension. It should be avoided abruptly canceling the piebifolium. An anesthesiologist must be informed that the patient is receiving nebivolol.

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.

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

Simultaneous use of nebivolol with baclofen and amifostine can cause a significant drop in blood pressure, so correction of the dose of antihypertensive drugs is required.

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

With the simultaneous use of sympathomimetic drugs suppress the effects 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 (for example, paroxetine, fluoxetine, thioridazine, quinidine, bupropion, levomepromazine, etc.), the concentration of pevbinol in the blood plasma increases, the metabolism of the piebifolium slows down, which may increase the risk of bradycardia and unwanted reactions.

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

With simultaneous use with digoxin nebivolol no impact on the pharmacokinetic parameters of digoxin.

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

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

Simultaneous ethanol, furosemide or hydrochlorothiazide does not affect the farmatokinetics nebivolol.

Nebivolol has no effect on the pharmacokinetics and pharmacodynamics of warfarin.

Special instructions:

Inadmissible abrupt discontinuation of beta-adrenoblockers (with a sudden cessation of treatment may develop the syndrome of "withdrawal"). Treatment with NEBOLOL-NANOLEC should be stopped gradually, reducing the dose for 10 days (up to 2 weeks in patients with coronary heart disease).

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 of NEBIVOLOL-NANOLEC should be reduced if, on the background of treatment, heart rate at rest becomes below 55 beats / min and / or the patient develops symptoms indicating a bradycardia.

Control of patients taking Nebivolol-Nanolek, includes monitoring the heart rate and blood pressure (at the beginning of the drug - every day, then I every 3-4 months).

Older patients need control of kidney function (once every 4-5 months).

NEBIVOLOL-NANOLEC should be used with caution in patients with chronic obstructive pulmonary disease, as bronchoconstriction may increase.

NEBIVOLOL-NANOLEC 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, since NEBIVOLOL-NANOLEC can mask certain symptoms of hypoglycemia (eg, palpitation, tachycardia) caused by the application hypoglycemic agents for oral administration and insulin. The control of the concentration of glucose in the blood plasma should be carried out I every 4-5 months. (in patients with diabetes mellitus).

With hyperthyroidism, NEBIVOLOL-NANOLEC can mask tachycardia. Abrupt withdrawal of the drug may cause an exacerbation of the symptoms of the disease and the development of thyrotoxic crisis.

When deciding on the use of NEBIVOLOL-NAPOLEK in patients with psoriasis, the intended use of the drug and the possible risk of exacerbation of psoriasis should be carefully correlated. Patients who use contact lenses should take into account that the use of NEBIVOLOL-NANOLEC may reduce the production of tear fluid.

Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions.

In smoking patients, the effectiveness of beta-blockers is lower compared to non-smokers.

In patients with pheochromocytoma, it is necessary to begin treatment with alpha-adrenoblockers prior to the use of any beta-blocker. When using the drug NEBIVOLOL-NANOLEK in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (unless an effective blockade of alpha-adrenergic receptors is previously achieved).

When conducting surgical interventions, the anesthetist should be warned that the patient is taking beta-blockers. Continuation of beta-adrenergic blockade reduces the risk of arrhythmias during introductory anesthesia and intubation.If, in preparation for the operation, it is necessary to interrupt the blockade of beta-adrenergic receptors, beta-blockers should be abolished at least 24 hours before the preparation for anesthesia.

Special precautions for the destruction of an unused drug NEBIVOLOL-NANOLEC.

There is no need for special precautions for the destruction of an unused drug NEBIVOLOL-NANOLEC.

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

The influence of nebivolol on the ability to drive vehicles and control mechanisms is not specifically studied. Studies of the pharmacodynamics of nebivolol have shown that the drug has no effect on the psychomotor function. During the period of treatment with NEBIVOLOL- HANOLEK should be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to the possible occurrence of dizziness and fatigue. The most likely occurrence of these phenomena at the beginning of the drug or after increasing the dose.

Form release / dosage:

Tablets 5 mg.

But 10 tablets in a contour mesh box made of a combined material of polyamide / aluminum / PVC and aluminum foil.

According to 1, 2, 3, 6 or 9 contour cell packs of 10 tablets, together with the instructions, they are placed in a cardboard box.

Packaging:(10) - packings, cellular, outline (1) - packs, cardboard
(10) - packings, cellular, outline (2) - packs, cardboard
(10) - packings, cellular, outline (3) - packs, cardboard
(10) - packings, cell planimetric (6) - packs cardboard
(10) - packings, cellular planimetric (9) - packs cardboard

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use at the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003049

Date of registration:19.06.2015

The owner of the registration certificate:NANOLEC, LTD. NANOLEC, LTD. Russia

Manufacturer: & nbsp

ZIM LABORATORIES, Ltd India

Representation: & nbspNANOLEC, LTD.NANOLEC, LTD.

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Nebivolol-Nanolek (Nebivolol-Nanolek)