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

Excipients: lactose monohydrate - 167.05 mg, corn pregelatinized corn starch - 35,50 mg, croscarmellose sodium - 6,00 mg, povidone - 6,00 mg, crospovidone - 3,00 mg, silicon dioxide colloid - 2,00 mg, magnesium stearate - 3.00 mg.

Description:Round, convex on one side and concave on the other side of a white tablet, with a cross-shaped risk on both sides and four triangular notches along the line of the scales.

Pharmacotherapeutic group:Beta1-adrenoblocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a lipophilic, cardioselective beta 1-adrenoblocker with vasodilating properties. It is a racemate consisting of two enantiomers: DNebivolol (SRRRnebivolol) and LNebivolol (RSSSNebivolol), combining two pharmacological actions:

- D-nibilol is a competitive and highly selective blocker of beta1-adrenergic receptors (affinity for beta 1-adrenergic receptors is 293 times higher than for beta2-adrenergic receptors;

- L- Nebivolol has a mild vasodilating effect due to the modulation of the release of the relaxing factor from the vascular endothelium.

It has antihypertensive, anti-anginal and antiarrhythmic effects. Reduces high blood pressure 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.

Antihypertensive effect is also due to a decrease in the activity of the renin-angiotensin converting enzyme (does not directly correlate with changes in renin activity in blood plasma). In the first days of treatment increases the overall peripheral resistance of the vessels, then, with prolonged use, it normalizes or decreases. Antihypertensive effect occurs after 2-5 days, stable effect is observed after 1 month. The effect persists with long-term treatment. The use of nebivolol improves the indices of systemic and intracardiac hemodynamics. Nebivolol reduces the heart rate and reduces high blood pressure at rest and during exercise, reduces the end-diastolic pressure of the left ventricle, reduces the overall peripheral vascular resistance, improves the diastolic function of the heart (reduces filling pressure), increases the ejection fraction.

Reducing the need for myocardium in oxygen (decreasing heart rate and reducing myocardial contractility), reduces the number and severity of angina attacks and increases 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:

Suction

After oral administration, both enantiomers of nebivolol are rapidly absorbed from the gastrointestinal tract. Eating does not affect absorption. Bioavailability averages 12% in patients with "fast" metabolism and is almost complete in patients with "slow" metabolism.

Distribution

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%, for L- nebivolol - 97.9%.

Metabolism

Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites. The metabolism of nebivolol occurs through epicyclic and aromatic hydroxylation, N-dealkylation and glucuronation, in addition, glucuronides of hydroxy metabolites are formed. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on CYP2D6. The metabolic rate does not affect the effectiveness of nebivolol.

Excretion

One week after taking 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 of nebivolol enantiomers from plasma is on average 10 hours. In patients with "slow" metabolism, these values increase 3-5 times.

In patients with "fast" metabolism, the half-life of hydroxy metabolites of both enantiomers from plasma is on average 24 hours; in patients with "slow" metabolism, these values are approximately 2-fold increased.Pharmacokinetic parameters do not have age and sex differences.

Indications:

- arterial hypertension;

- ischemic heart disease: prevention of attacks of stable angina pectoris;

chronic heart failure (as part of combination therapy).

Contraindications:

- increased sensitivity to nebivolol or other components of the drug and other beta-blockers;

- severe violations of liver function;

- acute heart failure;

- chronic heart failure in the stage of decompensation (requiring inotropic teparia);

- cardiogenic shock;

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

- atrioventricular blockade of II and III degree (without artificial pacemaker);

- bronchospasm and bronchial asthma in history;

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

- metabolic acidosis;

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

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

- depression;

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

- simultaneous administration with floktaphenin, sultopride;

- age to 18 years;

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

Carefully:

Severe renal insufficiency (creatinine clearance less than 20 ml / min), liver dysfunction, diabetes mellitus, hyperthyroidism, desensitizing therapy, weighed allergic anamnesis, psoriasis, peripheral circulatory disorders, first degree atrioventricular block, Prinzmetal angina, chronic obstructive disease lungs, patients of advanced age (over 65 years).

Pregnancy and lactation:

The use of Nebivolol Stada® in pregnancy is permissible if the expected benefit to the mother exceeds the potential risk to the fetus. The appointment of the drug in pregnancy is possible only on strict indications (in connection with the risk of developing bradycardia in the newborns, arterial hypotension, hypoglycemia and respiratory paralysis). The drug should be discontinued 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict observation of newborns within 48-72 hours after childbirth.

The use of the drug is not recommended during lactation. If it is necessary to use the drug, breastfeeding should be discontinued.

Dosing and Administration:

Inside, at the same time, regardless of food intake, without chewing and drinking with a sufficient amount of liquid.

Arterial hypertension and ischemic heart disease

The average daily dose is 5 mg (1 tablet 1 time / day). The optimal effect becomes pronounced after 1-2 weeks of treatment, in some cases - after 4 weeks.

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

It is possible to use the drug in the form of monotherapy or as part of combined antihypertensive therapy.

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. The maximum daily dose is 10 mg.

Elderly patients: for patients older than 65 years, the initial dose is 2.5 mg / day (1/2 tablets of 5 mg). If necessary, the daily dose can be increased to 5 mg. However, taking into account the limited experience of using 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 stable chronic heart failure should begin with a gradual increase in the dose to achieve an individual optimal maintenance dose. Patients should not have attacks of acute heart failure within the last 6 weeks. It is recommended to carry out treatment under close supervision of a doctor.

Patients who take diuretics, cardiac glycosides, angiotensin converting enzyme inhibitors, angiotensin II antagonists, dosing of drugs should be stabilized within 2 weeks. before the start of Nebivolol Stada® therapy.

To start treatment of chronic heart failure with beta-adrenergic blockers is necessary in a clinically stable state for the last 2 weeks. Each dose increase should be carried out not later than 2 weeks, depending on the individual sensitivity of the organism. Increase the dose from 1.25 mg / day (1/4 tablets of 5 mg) to 2.5 mg / day (1/2 tablets of 5 mg), then - to 5-10 mg / day (1-2 tablets 5 mg each). The maximum daily dose is 10 mg.

The beginning of therapy and every increase in the dose of the drug should be carried out under the strict supervision of the physician for at least the first 2 hours. During titration, regular monitoring of blood pressure, heart rate and symptoms of severe chronic heart failure is recommended. The occurrence of adverse reactions in all patients taking the maximum recommended dose can be prevented. If necessary, the dose achieved can be reduced and raised again.

During the titration phase, in case of worsening of the course of chronic heart failure or intolerance of the drug, it is recommended to reduce the dose of the drug or stop taking it.

Treatment of chronic chronic failure is usually prolonged. Treatment with drug Nebivolol Stade® is not recommended to be discontinued sharply, as this may lead to a temporary exacerbation of heart failure symptoms. If it is necessary to stop taking the drug, the cancellation is carried out gradually, reducing the dose during the week by half.

Patients with renal insufficiency: with mild and moderate renal disease

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 (creatinine level <25 ml / min), so its use in such patients is not recommended.

Patents of the elderly: there is no need to adjust the dose, so it is necessary to individually select the dose, gradually increasing to the maximum tolerable.

Side effects:

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

Disturbances from the nervous system:

Often: headache, dizziness, fatigue, weakness, paresthesia; Infrequently: depression, "nightmarish" dreams, confusion, insomnia;

Very rarely: faint, hallucinations.

Disorders from the gastrointestinal tract:

Often: nausea, constipation, diarrhea;

Infrequently: indigestion, flatulence, vomiting.

Disorders from the cardiovascular system:

Infrequently: aetiology, acute heart failure, heart block, orthostatic hypotension, Raynaud's syndrome, cardiac arrhythmias, peripheral edema, cardialgia, aggravation of chronic heart failure, expressed in blood pressure.

Disturbances from the skin and subcutaneous tissues:

Infrequent: skin rash of erythematous nature, itching;

Very rarely: exacerbation of psoriasis;

In some cases: angioedema.

Disturbances from the respiratory system:

Often: dyspnea;

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

Other:

Infrequent: visual impairment, impotence, photodermatosis, hyperhidrosis;

Rare: dryness of the mucous membrane of the eyes.

Overdose:

Symptoms: pronounced reduction in blood pressure, bradycardia, congestive heart failure, atrioventricular block, cardiogenic shock, cardiac arrest, bronchospasm, unconsciousness, convulsions, coma, nausea, vomiting, hypoglycemia, 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, intravenous fluid and vasopressors. 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. In case of atrioventricular blockade (P-S st.) Intravenous administration of beta-adrenostimulants is recommended, if they are ineffective, consider the issue of the 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. In bronchospasm, intravenous beta2-adrenomimetics are used. With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class). With convulsions - intravenous diazepam.

Interaction:

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.

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).

When used simultaneously with antiarrhythmic drugs of class I 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 the slowing of atrioventricular conduction was detected.

Simultaneous use of nebivolol and funds 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 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, anxiolytics, hypnotics, ethanol can enhance the antihypertensive effect of nebivolol.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. However, with the combined use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (palpitation, tachycardia) can be masked.

Contraindicated simultaneous reception with floktapheninom: nebivolol is capable to prevent compensatory reactions of the cardiovascular system associated with arterial hypotension or shock, which can be caused by floktaphenin.

Joint use of nebivolol with baclofen, amifostine leads to increased arterial hypotension.

When combined with sultopride, there is an increased risk of ventricular arrhythmia of the pirouette type.

Pharmacokinetic interaction

When used in conjunction with drugs that inhibit serotonin reuptake, or other drugs 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.

Rifampicin enhances the metabolism of nebivolol.

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increased slightly (which has no clinical significance). With the simultaneous use of nebivolol and ethanol, furosemide or hydrochlorothiazide, there is no change in the pharmacokinetic parameters 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:

It is unacceptable to suddenly stop taking beta-blockers (with the sudden cessation of treatment may develop the syndrome of "withdrawal"), treatment should be stopped if possible, gradually reducing the dose for 10 days (1-2 weeks in patients with coronary heart disease).

With stable angina, the chosen dose should provide a heart rate at rest in the range of 55-60 beats / min, with a load of 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.

Beta-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease, since it is possible to strengthen bronchospasm.

In smoking patients, the effectiveness of beta-blockers is lower.

Control of patients taking beta-blockers includes monitoring heart rate and blood pressure (at the beginning of administration - every day, then once every 3-4 months), blood glucose concentration in patients with diabetes (1 time in 4- 5 months).

In elderly patients it is recommended to follow the function of the kidneys (once every 4-5 months).

When hyperthyroidism masks tachycardia.

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

When deciding whether to prescribe a drug for patients with psoriasis, the expected benefits of using the drug and the possible risk of exacerbation of psoriasis should be carefully correlated.

Patients who use contact lenses should take into account that against the background of treatment with beta-adrenoblockers, tear production can be reduced.

If during therapy with the drug Nebivolol Stade® requires the patient to undergo a surgical procedure, it is necessary to inform the anesthesiologist about the nature of the therapy.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg. For 7 tablets in a planar cell box made of aluminum foil and PVC film.

2 or 4 contour mesh packages together with instructions for medical use of the drug are placed in a pack of cardboard.

Packaging:(7) - packings, cellular, outline (2) - packs, cardboard
(7) - packings, cellular, outline (4) - packs, cardboard

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001083

Date of registration:02.11.2011

Date of cancellation:2017-09-26

The owner of the registration certificate:SHTADA Artznajmittel AGSHTADA Artznajmittel AG Germany

Manufacturer: & nbsp

SHTADA Artznajmittel AG

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp26.09.2017

Illustrated instructions

Instructions

Nebivolol Stade® (Nebivolol Stada®)