Nebivator

General characteristics. Structure:

Active ingredient: 5 mg of a nebivolol.

Pharmacological properties:

Cardioselective beta1-adrenoblocker; has hypotensive, anti-anginal and antiarrhytmic effect. Reduces raised by the ABP at rest, at a physical tension and a stress. Competitively and selectively blocks synoptic and vnesinaptichesky beta1-adrenoceptors, doing them unavailable to catecholamines, modulates release of an endothelial vazodilatiruyushchy factor (NO). Hypotensive action is caused also by reduction of activity of RAAS (directly does not correlate with change of activity of a renin in plasma). In the first days of treatment increases OPSS, further, at prolonged use, it is normalized or decreases. The hypotensive effect occurs in 2-5 days, stable action is noted in 1-2 months. Reducing the need of a myocardium for oxygen (urezheny ChSS and decrease in contractility of a myocardium), reduces number and weight of attacks of stenocardia and increases portability of an exercise stress. Due to increase in end diastolic pressure in LZh and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with HSN. Antiarrhytmic action is caused by suppression of automatism of heart (including in the pathological center) and delay of AV of conductivity.

Pharmacodynamics. Cardioselective beta adrenoblocker III of generation with vazodilatiruyushchy properties. Active agent represents the racemate consisting of two enantiomer: D-nebivolola and L-nebivolola. Nebivolol is a competitive and selective blocker β1-адренорецепторов (affinity to β1-адренорецепторам is 288 times higher, than to β2-адренорецепторам), besides, has soft vazodilatiruyushchy effect due to modulation of release of the running-down factor (NO) from an endothelium of vessels. Nebivolol reduces ChSS and the ABP at rest and at loading, reduces the end diastolic pressure of a left ventricle, reduces OPSS, improves diastolic function of heart (reduces filling pressure), increases fraction of emission; causes anti-anginal effect in ischemic heart disease patients.

Optimal hypotensive effect is shown in 1-2 weeks of treatment. In certain cases the maximum effect is reached 4 weeks later.

Pharmacokinetics. After intake небиволол it is quickly absorbed from a GIT. Meal does not influence absorption. Bioavailability averages 12% at persons with bystry metabolism and is almost full at persons with slow metabolism.

Css in a blood plasma at most of patients (persons with bystry metabolism) is reached during 24 h, and for hydroxymetabolites - in several days. Concentration in plasma of 1-30 mkg/l are proportional to a dose.

Linkng with proteins of plasma (it is preferential with albumine) about 98%.

Nebivolol is actively metabolized, partially with formation of active hydroxymetabolites. Metabolism of a nebivolol happens by an alicyclic and aromatic hydroxylation, N-dealkylations and a glyukuronirovaniye, besides, are formed glucuronides of hydroxymetabolites. Speed of metabolism of a nebivolol by an aromatic hydroxylation is genetically determined by oxidizing polymorphism and depends on CYP2D6.

In a week after introduction of 38% (the amount of not changed active agent makes less than 0.5%) of a dose also 48% - through intestines are removed by kidneys.

At persons with bystry metabolism of T1/2 of a nebivolol from plasma averages 10 h, at persons with slow metabolism - is 3-5 times higher.

At persons with bystry metabolism of T1/2 value of hydroxymetabolites from plasma average 24 h, at persons with slow metabolism - is twice higher.

Indications to use:

Arterial hypertension, IBS, HSN (as a part of a combination therapy).

Route of administration and doses:

The adult for intake - 2.5-5 mg in the morning. The optimum effect develops in 1-2 weeks of treatment, and in some cases - in 4 weeks. If necessary the daily dose is increased to 10 mg.

For patients 65 years an initial dose are aged more senior makes 2.5 mg. If necessary it is possible to increase a daily dose to 5 mg.

Features of use:

Use during pregnancy. Use at pregnancy is possible only according to strict indications (in connection with possible development in newborns of bradycardia, arterial hypotension, a hypoglycemia and paralysis of breath). Reception of a nebivolol needs to be stopped for 48-72 h before childbirth. When it is impossible, it is necessary to provide strict observation of newborns during 48-72 h after the delivery.

With care to apply at patients with a renal failure, hyperfunction of a thyroid gland, allergic diseases, psoriasis, to persons 65 years and a sick diabetes mellitus are aged more senior.

Cancellation of beta adrenoblockers should be carried out gradually, within 10 days (up to 2 weeks at patients with an ischemic heart disease).

In an initiation of treatment it is necessary to control daily the ABP and ChSS.

Efficiency of beta adrenoblockers at smokers is lower, than at non-smoking.

Nebivolol does not exert impact on glucose level at patients with a diabetes mellitus, however under the influence of a nebivolol can be disguised certain signs of a hypoglycemia (tachycardia, tachycardia) caused by use of hypoglycemic drugs.

In need of use of a nebivolol for patients with psoriasis it is necessary to estimate carefully expected advantage of therapy and possible risk of an exacerbation of psoriasis.

Beta adrenoblockers should be applied with care at the increased function of a thyroid gland because under the influence of beta adrenoblockers tachycardia can it is leveled.

Nebivolol can strengthen symptoms of disturbance of peripheric circulation.

The patients carrying contact lenses have to consider that against the background of use of beta adrenoblockers decrease in products of the lacrimal liquid is possible.

When carrying out surgical interventions it is necessary to warn the anesthesiologist that the patient accepts beta adrenoblockers.

Control of content of glucose in a blood plasma it is necessary to carry out 1 time in 4-5 months (at patients with a diabetes mellitus).

Control of laboratory indicators of function of kidneys it is necessary to carry out 1 time in 4-5 months (at patients of advanced age).

Use for children is not recommended.

Influence on ability to driving of motor transport and to control of mechanisms. Nebivolol does not influence the speed of psychomotor reactions. Against the background of reception of a nebivolol dizziness and feeling of fatigue therefore the patients accepting небиволол should abstain from occupations potentially dangerous types of activity are sometimes possible.

Side effects:

From TsNS and peripheral nervous system: a headache, dizziness, feeling of fatigue, paresthesia, a depression, decline in the ability to concentration of attention, drowsiness, sleeplessness, dreadful dreams, hallucinations.

From the alimentary system: nausea, a lock, diarrhea, dryness in a mouth.

From cardiovascular system: bradycardia, orthostatic hypotension, asthma, hypostases, heart failure, AV blockade, disturbances of a heart rhythm, Reynaud's syndrome, cardialgias.

Allergic reactions: skin rash.

Others: a bronchospasm (including in the absence of obstructive diseases of lungs in the anamnesis), a photodermatosis, a hyperhidrosis, rhinitis.

Interaction with other medicines:

At simultaneous use with antiarrhytmic drugs I of a class, Amiodaronum strengthening of negative inotropic effect and oppression of AV conductivity is possible.

At simultaneous use with blockers of calcium channels (verapamil and diltiazem) negative inotropic effect and oppression of AV conductivity amplifies.

At in administration of verapamil against the background of reception of a nebivolol there is a threat of a cardiac standstill.

At simultaneous use with sympathomimetics pharmacological activity of a nebivolol is suppressed.

At simultaneous use with anesthetics suppression of reflex tachycardia and increase in risk of development of arterial hypotension is possible.

At simultaneous use with tricyclic antidepressants, barbiturates, derivatives of a fenotiazin strengthening of anti-hypertensive action of a nebivolol is possible.

At simultaneous use with Cimetidinum increase in concentration of a nebivolol in a blood plasma is possible.

Contraindications:

Bronchial asthma, chronic heart failure in a decompensation stage, not treated pheochromocytoma, heavy abnormal liver functions, depressions, angiospastic stenocardia (Printsmetal's stenocardia), obliterating diseases of peripheral vessels (a syndrome alternating lameness), arterial hypotension, cardiogenic shock, bradycardia (ChSS less than 50 уд. / mines), SSSU, AV blockade of II and III degrees, a myasthenia, muscular weakness, children's and teenage age up to 18 years, hypersensitivity to a nebivolol.

Storage conditions:

List B. In the place protected from light, at a temperature not above 25 °C. A period of validity - 24 months.

Issue conditions:

According to the recipe

Packaging:

On 10 pieces of tablets - planimetric strip packagings (10) - packs cardboard.