Composition, form of production and packaging
Tablets are white or almost white, biconvex, with a cruciform risk.
nebivolol hydrochloride 5.45 mg,
which corresponds to the content of nebivolol 5 mg
Auxiliary substances: giprolose (hydroxypropylcellulose) - 5 mg, calcium hydrophosphate dihydrate - 55.5 mg, silicon dioxide colloid (aerosil) - 0.7 mg, croscarmellose sodium (impellose) - 3 mg, lactose monohydrate (sugar milk) - 33.75 mg, vegetable oil hydrogenated - 0.6 mg, microcrystalline cellulose - 35 mg, magnesium stearate - 1 mg.
7 pcs. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
7 pcs. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
7 pcs. - Cellular outline packaging (aluminum / PVC) (4) - cardboard packs.
7 pcs. - Cellular outline packaging (aluminum / PVC) (8) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (6) - cardboard packs.
30 pcs. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
30 pcs. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Cardioselective lipophilic beta- 1- adrenoblocker III generation with vasodilating properties. Has antihypertensive, anti-anginal and antiarrhythmic effect. 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 endothelial vasodilating factor nitric oxide (NO).
Nebivolol is a racemate consisting of two enantiomers: SRRR-nebivolol (D-nebivolol) and RSSS-nebivolol (L-nebivolol), which combines 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 exerts a vasodilating effect by modulating the release of the relaxing factor (NO) from the vascular endothelium.
The hypotensive effect develops on the 2nd-5th day of treatment, the stable effect is observed after 1 month, remains with prolonged treatment.
The hypotensive effect is also due to a decrease in the activity of RAAS (does not directly correlate with a change 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.
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.
Binding to blood plasma proteins (mainly with albumin) for D-nebivolol is 98.1%, and for L-nebivolol - 97.9%.
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 isoenzyme CYP2D6.
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 values вЂ‹вЂ‹of T 1/2 enantiomers of nebivolol from the 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 T 1/2 values вЂ‹вЂ‹of the hydroxymetabolites of both enantiomers from the blood plasma are on average 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 (CHF) (as part of combination therapy).
The drug is taken orally, at the same time of the day, regardless of food intake. Tablets should be swallowed without chewing and drinking with a sufficient amount of liquid.
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 as a 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 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.
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.
Treatment of chronic heart failure should begin with a gradual increase in the dose until an individual optimal maintenance dose is achieved.
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 Nebivolol Canon (1/4 tablets of 5 mg) 1 time / day can be increased first to 2.5-5 mg of Nebivolol Canon (1/2 tablets of 5 mg-1 tablets), 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 subsequent increase in the dose. Each dose increase should be carried out at least 2 weeks later. The maximum recommended dose for CHF therapy is 10 mg of Nebivolol Canon 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 to the drug, it is recommended to reduce the dose of Nebivolol Canon or, if necessary, immediately stop taking it (in case of pronounced arterial hypotension, worsening of CHF flow with acute pulmonary edema, development of cardiogenic shock, symptomatic bradycardia or AV-blockade).
From the side of the central nervous system: headache, dizziness, fatigue, paresthesia, depression, decreased ability to concentrate, drowsiness, insomnia, nightmares, hallucinations.
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 .
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.
On the part of the digestive system: nausea, constipation, flatulence, diarrhea, dryness of the oral mucosa.
From the skin and subcutaneous tissues: photodermatosis, hyperhidrosis, exacerbation of psoriasis.
Allergic reactions: skin itching, eruptive rash.
1 - this side effect predominantly occurs during the titration of the dose of the drug.
- pronounced violations of the liver function;
- 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);
- pronounced bradycardia (heart rate less than 50 beats per minute);
- arterial hypotension;
- severe severe disturbances of peripheral circulation (intermittent claudication, Raynaud's syndrome);
- bronchospasm and bronchial asthma;
- pheochromocytoma (without simultaneous use of alpha-blockers);
- age up to 18 years;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (the preparation contains lactose);
- simultaneous use 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), liver function disorders, diabetes mellitus, hyperthyroidism, desensitizing therapy, psoriasis, grade I AV block, Prinzmetal angina, COPD, elderly patients 65 years old).
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 with breast milk. Therefore, the use of Nebivolol Canon is not recommended for women during lactation. If Nebivolol Canon is used during lactation, then breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
Caution should be given to patients with severe renal failure (CC less than 20 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should prescribe the drug to patients with impaired liver function.
The use of the drug in patients with severe hepatic impairment is contraindicated.
APPLICATION FOR CHILDREN
The use of the drug in children and adolescents under the age of 18 is contraindicated.
APPLICATION IN ELDERLY PATIENTS
With caution should prescribe the drug to elderly patients (over 65 years).
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 whether to use Nebivolol Canon, patients with psoriasis should carefully correlate the perceived 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 conducting surgical procedures, an anesthesiologist should be warned that the patient is taking nebivolol.
Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, caution should be exercised in the treatment of such 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.
The effectiveness of beta-blockers 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 insufficient 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. In the event of such effects, the patient should not drive vehicles or engage in potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions. These effects occur most often immediately after the start of treatment or with increasing doses.
Symptoms: excessive decrease in blood pressure, pronounced bradycardia, AV blockade, cardiogenic shock, acute heart failure, cardiac arrest, bronchospasm, unconsciousness, coma, nausea, vomiting, cyanosis.
Treatment: gastric lavage, reception of activated charcoal. In the case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with a low headboard, if necessary - intravenous fluid and vasopressors.
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 2 -adrenomimetiki.
With ventricular extrasystole - lidocaine (do not administer antiarrhythmic drugs IA class).
In the case of shock or arterial hypotension caused by the use of floktaphenina, beta-adrenoblockers weaken the compensatory mechanisms of the cardiovascular system.
With simultaneous use with sultopride, the risk of ventricular arrhythmia increases, especially in the form of "pirouette" (torsade des pointes).
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 increases. Contraindicated in / in the administration of verapamil on the background of nebivolol. When combined with antihypertensive agents, nitroglycerin, or blockers of slow calcium channels, 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 agents biotransforming with the participation of the isoenzyme CYP2D6, 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.
The simultaneous use 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 out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 2 years.