Composition, form of production and packaging
The tablets are almost white, round, biconvex, with a crosswise dividing risk on one side.
nebivolol hydrochloride 5.45 mg,
which corresponds to the content of nebivolol 5 mg
Excipients: lactose monohydrate - 83.45 mg, corn starch - 18 mg, croscarmellose sodium - 5.4 mg, polysorbate 80 - 0.22 mg, hypromellose - 1.8 mg, silicon dioxide colloid - 0.23 mg, cellulose microcrystalline - 30 mg, magnesium stearate - 0.45 mg .
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Nebivolol is a lipophilic, cardioselective beta- 1- adrenoblocker of the third generation with vasodilating properties. It has antihypertensive, anti-anginal and antiarrhythmic effects. Reduces elevated blood pressure at rest, with physical stress and stress. Competently and selectively blocks synaptic and postsynaptic? 1-adrenoreceptors, making them inaccessible to catecholamines, modulates the release of the endothelial relaxant nitric oxide factor.
Nebivolol is a racemate consisting of two enantiomers: SRRR - nebivolol (D-nebivolol) and RSSS-nebivolol (L-nebivolol), combining two pharmacological actions:
- D-nebivolol is a competitive and highly selective blocker? 1- adrenoreceptors (affinity for? 1- adrenoreceptors is 293 times higher than for ОІ2-adrenoreceptors).
- L-nebivolol has a vasodilating effect due to modulation of endothelial a relaxing factor of nitric oxide 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 the blood plasma).
The use of nebivolol improves the indices of systemic and intracardiac hemodynamics. Nebivolol reduces the heart rate at rest and with physical activity, reduces the end-diastolic pressure of the left ventricle, lowers the OPSS, improves diastolic function of the heart (reduces filling pressure), increases the ejection fraction, reduces the myocardial mass and myocardial mass index.
Reducing the need for myocardium in oxygen (decreasing heart rate, reducing preload and afterload), reduces the number and severity of angina attacks and improves the tolerance of exercise.
Antiarrhythmic action is due to the suppression of the automatism of the heart (including in the pathological focus) and the slowing of AV conduction.
Suction and distribution
After ingestion, nebivolol is rapidly absorbed from the digestive tract. Eating does not affect suction, so nebivolol can be taken regardless of food intake.
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 blood plasma of 1-30 mcg / l are proportional to the dose.
The association with blood plasma proteins (predominantly with albumin) for D-nebivolol is 98.1%, and for L-nebivolol, 97.9%.
Metabolism and excretion
Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the CYP 2D6 isoenzyme.
After the administration 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 T 1/2 values вЂ‹вЂ‹of the enantiomers of nebivolol from plasma are an average of 10 hours. In patients with "slow" metabolism, these values вЂ‹вЂ‹increase 3-5 times.
In patients with "fast" metabolism, the values вЂ‹вЂ‹of T 1/2 hydroxymetabolites of both enantiomers from blood plasma averagely 24 hours, in patients with a "slow" metabolism these values вЂ‹вЂ‹are approximately 2-fold increased.
The pharmacokinetics of nebivolol is not affected by age and sex of patients.
- arterial hypertension;
- IHD: prevention of attacks of stable angina pectoris;
- chronic heart failure (as part of combination therapy).
The drug OD-Neb should be taken inside at the same time of the day, regardless of food intake, without chewing and drinking with a sufficient amount of liquid.
Hypertension and coronary artery disease
The average daily dose for the treatment of hypertension and ischemic heart disease is 5 mg (1 tab.) 1 time / 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, the daily dose can be increased to 10 mg (2 tablespoons of 5 mg at a time). 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 (1/2 tablespoons of 5 mg). If necessary, increase the dose to 5 mg.
At the expressed infringements of function of kidneys (KK less than 20 ml / mines) and at patients with serious diseases of a liver the maximum daily dose makes 10 mg.
Increasing the dose in these patients should be done with extreme caution.
Chronic heart failure
Treatment of chronic heart failure should begin with a gradual 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, maintaining two-week intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg of OD-Neb (1/4 tablets of 5 mg) 1 time / day can be increased first up to 2.5-5 mg of OD-Neb preparation (1/2 tablets of 5 mg - 1 tablet), and then - up to 10 mg (2 tablets of 5 mg) 1 time / 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 the subsequent increase in the dose. Each dose increase should be carried out not later than 2 weeks. Maximum the recommended dose for CHF therapy is 10 mg OD-Neb preparation 1 time / day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.
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 OD-Neb preparation or, if necessary, to stop it immediately (in case of pronounced arterial hypotension, worsening of CHF flow with acute pulmonary edema, in case of cardiogenic shock development , symptomatic bradycardia, or AV blockade).
From the nervous system: headache, dizziness, fatigue, paresthesia, depression, decreased ability to concentrate, drowsiness, insomnia, nightmares, hallucinations, confusion, fainting.
On the part of the digestive system: nausea, constipation, flatulence, diarrhea, dryness of the oral mucosa.
From the cardiovascular system: bradycardia, heart failure, AV blockade, orthostatic hypotension, peripheral circulatory disorders, shortness of breath, heart rhythm disturbances, Raynaud's syndrome, peripheral edema, cardialgia, worsening of CHF 1 .
From the skin: skin itch, rash erythematous nature.
On the part of the respiratory system: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis), bronchospasm in patients with bronchial asthma or airway obstruction in anamnesis, rhinitis.
Allergic reactions: angioedema, hives, allergic vasculitis.
Other: photodermatosis, hyperhidrosis, exacerbation of psoriasis, dryness of the mucous membrane of the eye.
1 - this side effect predominantly occurs during the titration of the drug dose.
severe hepatic impairment;
- acute heart failure;
- cardiogenic shock;
- Chronic heart failure in the stage of decompensation (requiring inotropic therapy);
- SSSU, including sinoatrial blockade;
- AV blockade II and III degree (without artificial pacemaker);
- bronchospasm and severe forms of bronchial asthma;
- pheochromocytoma (without simultaneous use of alpha-blockers):
- pronounced bradycardia (heart rate less than 50 beats per minute);
- arterial hypotension;
- severe violations of peripheral circulation ("intermittent" lameness, Raynaud's syndrome);
- age up to 18 years;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose);
- simultaneous administration with floktaphenin, sultopride;
- Hypersensitivity to nebivolol or one of the components of the drug.
Caution should be applied to the drug with severe renal failure (CC less than 20 ml / min), violations of liver function of mild to moderate severity, diabetes mellitus, hyperthyroidism, desensitizing therapy, psoriasis, AV-blockade of I degree, angina Primaletal, chronic obstructive disease lungs, in elderly patients (over 65 years).
PREGNANCY AND LACTATION
In pregnancy, the drug is prescribed only on strict indications, when the benefit to the mother exceeds the risk for the fetus (in connection with the possible development of a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory paralysis). Treatment should be interrupted for 48-72 hours before childbirth. 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 OD-Neb is not recommended for women during lactation. If the use of OD-Neb during lactation is necessary, then breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with renal insufficiency, the initial dose is 2.5 mg / day (1/2 tablets of 5 mg). If necessary, increase the dose to 5 mg.
At the expressed infringements of function of kidneys (KK less than 20 ml / mines) the maximum daily dose makes 10 mg.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with severe liver disease, the maximum daily dose is 10 mg.
Contraindicated use in severe violations of liver function. With caution should be used for violations of liver function of mild to moderate severity.
APPLICATION FOR CHILDREN
Contraindicated for children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
In patients over the age of 65, the initial dose is 2.5 mg / day (1/2 tablets of 5 mg). If necessary, increase the dose to 5 mg.
The abolition of beta-blockers 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 beats / min, with a load - 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 bpm.
When deciding on the use of OD-Neb preparation, patients with psoriasis should carefully correlate the intended use of the drug and the possible risk of exacerbation of psoriasis.
Patients using contact lenses should take into account that the production of beta-blockers may reduce the production of tear fluid.
Before performing the surgery, the anesthetist should be warned that the patient is taking nebivolol.
OD-Neb 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 nebivolol may mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents. Controlling 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 increase.
With hyperfunction of the thyroid gland, the drug levels tachycardia.
Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Such patients may not be immune to the usual doses of epinephrine used to stop them.
The effectiveness of beta-adrenoblockers in smokers is lower than in non-smoking patients.
Impact on the ability to drive vehicles and manage mechanisms
Research has shown that nebivolol has no effect on the rate of psychomotor reactions. Pilots flying crew with arterial hypertension I degree (admitted to flight work), the drug is prescribed in an initial dose of 2.5 mg. In the future (no earlier than 2 weeks) with good tolerability of treatment and sufficient control of blood pressure, a 2.5 mg dose increase is possible. The recommended dose is 5 mg / day. Some patients may experience side effects, most often dizziness, due to lowered blood pressure. If such effects occur, the patient should not drive vehicles or engage in potentially hazardous activities requiring special attention and speed of psychomotor reactions. These effects occur most often immediately after the start of treatment or with increasing doses.
Symptoms: nausea, vomiting, cyanosis, marked decrease in blood pressure, pronounced bradycardia, bronchospasm, AV blockade, cardiogenic shock, acute heart failure, loss of consciousness, coma, cardiac arrest.
Treatment: gastric lavage, reception of activated charcoal. In the case of a pronounced decrease in blood pressure it is necessary to give the patient a horizontal position with raised legs, if necessary, intravenous plasmasubstitutional solutions and vasopressors are introduced.
When bradycardia is expressed, intravenous injection of 0.5-2 mg of atropine is administered, in the absence of a positive effect, a transvenous artificial pacemaker is available.
With AV-blockade (II-III st.) It is recommended to / in the introduction of beta-adrenomimetics, 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, it is advisable to administer dopamine, dobutamine or vasodilators. When bronhospazme enter in / in beta-adrenomimetiki. With ventricular extrasystole - lidocaine (do not administer antiarrhythmic drugs IA class).
Floktaphenin: in the case of shock or arterial hypotension caused by floktaphenin pritm, beta-adrenoblockers weaken the compensatory mechanisms of the cardiovascular system.
Sultopride: increased risk of ventricular arrhythmias, especially as pirouettes.
With the simultaneous use of beta-blockers with slow calcium channel blockers (verapamil and diltiazem) , the effect on contractility of the myocardium and AV-conduction is increased. Contraindicated in / in the administration of verapamil on the background of nebivolol. When combined with antihypertensive drugs, nitroglycerin or BCCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin).
With simultaneous use with antiarrhythmic agents of the first class 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, there was no evidence of an increase in the effect on AV conduction slowing.
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 interaction of nebivolol and NSAIDs is not established. Acetylsalicylic acid as 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.
When used simultaneously with drugs that inhibit serotonin reuptake, or other means, biotransforming with the participation of isoenzyme CYP 2D6, the metabolism of nebivolol slows down.
With simultaneous use nebivolol had no effect on 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.
With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increased slightly, but this has no clinical significance.
Simultaneous administration of ethanol, furosemide or hydrochlorothiazide did not affect the pharmacokinetics 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.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light, out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years.