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

1 tablet contains:
active substance: nebivolol - 5.00 mg (in terms of nebivolol hydrochloride 5.45 mg); Excipients: lactose monohydrate - 142.00 mg; corn starch - 46.00 mg; croscarmellose sodium - 13.80 mg; microcrystalline cellulose - 16.31 mg; hypromellose - 4.60 mg; silicon dioxide colloidal - 0.65 mg; magnesium stearate 1.15 mg.

Description:Round, biconvex tablets white or almost white with a cross-shaped risk on one side.

Pharmacotherapeutic group:beta1-blocker selective.

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a cardioselective beta-blocker-blocker of the third generation with vasodilating properties. Has antihypertensive, anti-anginal and antiarrhythmic effect. Nebivolol reduces heart rate and lowers blood pressure 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 the final diastolic filling pressure of the left ventricle), increases the ejection fraction.Competitively and selectively blocks synaptic and postsynaptic beta] -adrenoceptors, making them inaccessible to catecholamines, modulates the release of endothelial vasodilating factor-nitric oxide (N0). Nebivolol is a racemate consisting of two enantiomers: SRRRNebivolol (Dnebivolol) and RSSSNebivolol (LNebivolol), combining two pharmacological actions:

- D- Nebivolol is a competitive and highly selective beta] -adrenoceptor blocker;

- 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, a stable effect is observed after 1 - 2 months. 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).

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

Antiarrhythmic effect is due to the suppression of the heart's automaticity (including in the pathological focus) and the slowing of atrioventricular conduction.

Pharmacokinetics:

After oral administration nebivolol quickly absorbed from the gastrointestinal tract (GIT). Eating does not affect suction, so nebivolol can be taken regardless of food intake. Bioavailability averages 12% in patients with "fast" metabolism (the effect of "primary transmission") and is almost complete in patients with "slow" metabolism.

Connection with blood plasma proteins (mainly with albumin) for DThe nebivolol is 98.1%, and for L- nebivolol - 97.9%. Metabolized with the formation of active metabolites, by acyclic and aromatic hydroxylation and partial A-dealkylation, the hydroxy- and amino derivatives formed are conjugated to glucuronic acid and are derived as ABOUT- and A-glucuron.

38% of the total dose of the drug is excreted by the kidneys (the amount of unchanged active substance is less than 0.5%) and 48% - through the intestine.

In patients with "fast" metabolism, the half-life of enantiomers of nebivolol from plasma is an average of 10 hours. In patients with "slow" metabolism, the value increases by 3 to 5 times. In patients with "fast" metabolism, the half-life of hydroxyl metabolites of both enantiomers from plasma is an average of 24 hours, in patients with "slow" metabolism this value is approximately 2-fold increased.

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

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

Indications:

- arterial hypertension;

- ischemic heart disease (CHD): prevention of seizures angina pectoris tension;

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

Contraindications:

- hypersensitivity to nebivolol or any of the components of the drug;

- severe hepatic impairment;

- acute cardiac insufficiency, 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 (in the absence of an artificial pacemaker);

- bronchial asthma or bronchospasm in the anamnesis;

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

- depression;

- metabolic acidosis;

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

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

- myasthenia gravis, muscle weakness;

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

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

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

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

- lactation period.

Carefully:

Severe renal insufficiency (creatinine clearance less than 20 ml / min), diabetes mellitus, hyperthyroidism, desensitizing therapy, psoriasis, allergic anamnesis, atrioventricular block I degree, CHF, Prinzmetal angina,chronic obstructive pulmonary disease (COPD), and elderly patients (over 65 years of age).

Pregnancy and lactation:

In pregnancy, the drug Nebivolol Sandoz® is prescribed only on strict indications, when the benefit to the mother exceeds the risk for the fetus (due to the possibility of delayed fetal growth, fetal death, premature birth, and development of a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory paralysis). Treatment should be discontinued 48 to 72 hours before delivery. In cases where this is not possible, it is necessary to monitor uteroplacental blood flow and fetal growth, as well as to ensure strict observation of the newborn during the first 3 days after delivery.

Studies in animals have shown that nebivolol excreted in breast milk. If the use of the drug Nebivolol Sandoz® during lactation is necessary, then breastfeeding should be discontinued.

Dosing and Administration:

A drug Nebivolol Sandoz® should be taken orally at the same time of the day, regardless of food intake, without chewing and drinking with a sufficient amount of liquid.

The tablet can be divided into four equal parts according to the cruciform risk. Arterial hypertension and ischemic heart disease

The average daily dose for the treatment of arterial hypertension and coronary artery disease is 2.5-5 mg (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. 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.

Patients with renal insufficiency:

the initial dose is 2.5 mg / day (1/2 tablet of 5 mg). If necessary, the daily dose can be increased to 5 mg.

Older patients:

for patients older than 65 years, the initial dose is 2.5 mg / day (1/2 tablet of 5 mg). If necessary, the daily dose can be increased to 5 mg. However, taking into account the limited experience of the drug in elderly patients, it is necessary to be cautious and conduct a thorough examination of patients over the age of 65 years. Chronic heart failure

Treatment of CHF should begin with a gradual titration of the dose until an individual optimal maintenance dose is achieved.

Selection of the dose at the beginning of treatment should be carried out in stages. Each dose increase should be carried out not later than 2 weeks, depending on the individual sensitivity of the organism: dose, which is 1.25 mg of the drug Nebivolol Sandoz® (1/4 tablets of 5 mg) once a day, can be increased first to 2.5-5 mg of the drug Nebivolol Sandoz® (1/2 tablets of 5 mg - 1 tablet of 5 mg), 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. The maximum recommended dose for CHF therapy is 10 mg of the drug Nebivolol Sandoz® once a day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.

During titration, in case of worsening of CHF flow or intolerance of the drug, it is recommended to reduce the dose of the drug Nebivolol Sandoz® or, if necessary, immediately stop taking it (in case of pronounced arterial hypotension,with worsening of the course of CHF with acute pulmonary edema, in case of development of cardiogenic shock, symptomatic bradycardia or atrioventricular blockade).

Treatment with drug Nebivolol Sandoz® is not recommended to stop abruptly (if this is not necessary), because this can lead to a transient worsening of the course of heart failure. If necessary, the dose should be reduced gradually (half every week).

For patients receiving medication for cardiovascular disease, including diuretics, digoxin, angiotensin-converting enzyme inhibitors and / or angiotensin II receptor antagonists, prior to initiation of drug treatment Nebivolol Sandoz® should stabilize the dose of these drugs in the past two weeks.

Patients with renal insufficiency:

with mild and moderate renal failure (CK> 20 ml / min), there is no need to adjust the dose, so it is necessary to select the dose individually, gradually increasing to the maximum tolerable. There is no experience of using the drug in patients with severe renal dysfunction (CC <20 ml / min), so its use in such patients is not recommended.

Older patients:

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

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> = 1/10), often (> = 1/100, <1/10), infrequently (> = 1 / 1000, <1/100), rarely (> = 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

From the immune system

frequency is unknown, angioedema, hypersensitivity.

From the central nervous system

often: headache, dizziness, increased fatigue,

paresthesia;

infrequently: "nightmarish" dreams, depression; rarely: syncope.

From the side of the organ of vision

infrequently: impaired vision (dry eyes).

From the side of the cardiovascular system

often: peripheral edema;

infrequently: bradycardia, heart failure, deceleration atrioventricular conduction / atrioventricular blockade, orthostatic hypotension, exacerbation of "intermittent" lameness.

From the respiratory system

often: dyspnea; infrequently: bronchospasm.

From the gastrointestinal tract often: nausea, constipation, diarrhea;

infrequently: indigestion, flatulence, vomiting.

From the skin and subcutaneous tissue is infrequent: skin itch, erythematous rash; rarely: exacerbation of psoriasis.

From the side of the reproductive system

infrequently: erectile disfunction.

With the use of some beta-adrenergic receptor antagonists, the following adverse reactions have also been described: hallucinations, psychosis, confusion, cooling / cyanosis of the extremities, Raynaud phenomenon.

Overdose:

Symptoms: pronounced bradycardia, atrioventricular block, cardiogenic shock, acute heart failure, cardiac arrest, bronchospasm, loss of consciousness, coma, nausea, vomiting, cyanosis, hypoglycemia.

Treatment: gastric lavage, reception of activated carbon. In the case of a pronounced reduction in blood pressure, the patient should be given a "lying" position with raised legs, if necessary, with / injection of liquid and vasopressors; as a follow-up, it is possible to administer glucagon (50-100 μg / kg).

With severe bradycardia, intravenously injecting 0.5-2 mg of atropine, in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be administered.

With atrioventricular blockade (II - III century), it is recommended to inject beta-adrenomimetics intravenously, in case of their ineffectiveness, the question of setting an artificial pacemaker should be considered. 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.

When hypoklikemia is recommended intravenous administration of a solution of dextrose (glucose).

Interaction:

Contraindicated simultaneous appointment of nebivolol and floktaphenina. There is a threat of developing arterial hypotension or shock. Contraindicated simultaneous administration of nebivolol and sultopride in connection with an increased risk of ventricular tachycardia.

With simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) increases the negative effect on myocardial contractility and atrioventricular conductivity. Contraindicated intravenous administration of verapamil against nebivolol.

Simultaneous use of nebivolol and BCCC dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, 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 combined with antihypertensive drugs, nitroglycerin can develop severe arterial hypotension (special caution is necessary when combined with prazosin).

With simultaneous use 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 sudden withdrawal of these drugs, especially before the abolition of nebivolol, it is possible to develop a "ricochet" arterial hypertension.

With simultaneous use with antiarrhythmic drugs I class (quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone) and with amiodarone, an increase in the negative inotropic effect and prolongation of the time through the atrioventricular node is possible.

The simultaneous use of nebivolol with cardiac glycosides can cause a slowdown of atrioventricular conduction.

The simultaneous use of nebivolol and drugs 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.

The simultaneous use of baclofen and amifostine with antihypertensive drugs can cause a significant drop in blood pressure, so a dose adjustment of antihypertensive drugs is required. Simultaneous use of insulin and hypoglycemic drugs for oral administration may mask certain symptoms of hypoglycemia (heart palpitations, tachycardia).

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

When used simultaneously with drugs that inhibit serotonin reuptake, or other means that are biotransforming with the participation of an isoenzyme CYP2D6 (eg, paroxetine, fluoxetine, thioridazine, quinidine), the metabolism of nebivolol slows down.

With the simultaneous use of nebivolol with nicardipine, the concentrations of both substances in the blood plasma increase slightly without changing the clinical effect.

The simultaneous administration of ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

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

With simultaneous use with cimetidine, nebivolol concentration in the blood plasma can be increased.

Special instructions:

Inadmissible abrupt discontinuation of beta-blockers, the abolition of beta-blockers should be carried out gradually, within 10 days (up to 2 weeks in patients with ischemic heart disease).

The effectiveness of beta-blockers in smokers is lower than that of non-smokers.

Control of blood pressure and heart rate at the beginning of the drug should be daily, then 1 every 3 to 4 months.

Older patients need control of kidney function (1 every 4 to 5 months).

With angina pectoris, the dose of the drug should provide a heart rate at rest in the range of 55-60 beats per minute, 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 beats / min (see section "Contraindications").

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 Sandoz®.

Nebivolol Sandoz® 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, palpitation, tachycardia) caused by the use of hypoglycemic agents.

Beta-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease, as bronchospasm may increase.

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

In patients with diabetes mellitus, the concentration of glucose in the blood plasma should be monitored once every 4 to 5 months.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused preparation Nebivolol Sandoz®.

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

During the period of drug treatment, care should be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 5 mg.

Packaging:

For 7 or 10 tablets are placed in the Al / PVC blister.

For 1, 2, 4 or 14 blisters of 7 tablets are placed in a cardboard box along with instructions for medical use.

For 1, 2, 3, 6 or 9 blisters of 10 tablets are placed in a cardboard box together with instructions for medical use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

Shelf life 3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001807

Date of registration:24.08.2012

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ ILAC SANAYI VE TICARET, A.S. Turkey

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Nebivolol Sandoz® (Nebivolol Sandoz®)