Binelol

General characteristics. Structure:

Active agent: небиволол (in the form of a nebivolol of a hydrochloride) - 5,00 mg;

Excipients: lactoses monohydrate, кросповидон (type A), half-oxameasures 188, K-30 povidone, cellulose microcrystallic, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Nebivolol is lipophilic, cardioselective beta adrenoblocker of the third generation with vazodilatiruyushchy properties. Has hypotensive, anti-anginal and antiarrhytmic effect. Reduces the increased arterial pressure (AP) at rest, at a physical tension and a stress. Competitively and selectively blocks synoptic and postsynaptic β1-adrenoceptors, doing them unavailable to catecholamines, modulates release of an endothelial vazodilatiruyushchy factor of nitrogen oxide (N0).
Nebivolol represents the racemate consisting of two enantiomer: SRRR небиволола (D-nebivolola) and RSSS небиволола (L-nebivolola), combining two pharmacological actions:

- D-nebivolol is a competitive and high-selection blocker of beta1-adrenoceptors (affinity to β1-адренорецепторам is 293 times higher, than to β2-адренорецепторам).
- L-nebivolol has soft vasodilating effect due to modulation of release of the running-down factor (N0) from an endothelium of vessels.
The hypotensive effect develops for 2-5 day of treatment, stable action is noted in 1 month. The anti-hypertensive effect remains at prolonged treatment.
Hypotensive action is caused also by activity reduction a renin - angiotenzinovy system (directly does not correlate with change of activity of a renin in a blood plasma).
Use of a nebivolol improves indicators of a system and endocardiac hemodynamics. Nebivolol urezhat the heart rate (HR) and the ABP at rest and at an exercise stress, reduces the end diastolic pressure of a left ventricle, reduces the general peripheric vascular resistance, improves diastolic function of heart (reduces filling pressure), increases fraction of emission.
Reducing the need of a myocardium for oxygen (urezheny ChSS, decrease in preloading and afterload), reduces quantity and weight of attacks of stenocardia and increases portability of an exercise stress.
Antiarrhytmic action is caused by suppression of pathological automatism of heart (including in the pathological center) and delay of AV of conductivity.

Pharmacokinetics. Absorption. After intake небиволол are quickly absorbed from digestive tract. Meal does not influence absorption therefore небиволол it is possible to accept irrespective of meal. Bioavailability averages 12% at patients with "bystry" metabolism and is almost full at patients with "slow" metabolism. Efficiency of a nebivolol does not depend on metabolism speed.

Distribution. The clearance in a blood plasma at most of patients (with "bystry" metabolism) is reached during 24 h and for hydroxymetabolites - in several days. Concentration in a blood plasma of 1-30 mkg/l are proportional to a dose.
Communication with proteins of a blood plasma (it is preferential with albumine) for D-nebivolola makes 98,1%, and for L-nebivolola - 97,9%.

Metabolism. Nebivolol is actively metabolized, partially with formation of active hydroxymetabolites. Speed of metabolism of a nebivolol by an aromatic hydroxylation is genetically determined by oxidizing polymorphism and depends on CYP2D6 isoenzyme.

Removal. 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 patients with "bystry" metabolism of value of an elimination half-life (T1/2) of enantiomer of a nebivolol from a blood plasma average 10 h. At patients with "slow" metabolism these values by 3-5 times increase.
At patients with "bystry" metabolism of T1/2 value of hydroxymetabolites of both enantiomer from a blood plasma average 24 h, at patients with "slow" metabolism these values increase approximately twice.
The pharmacokinetics of a nebivolol is not influenced by age and a sex of patients.

Indications to use:

Coronary Heart Disease (CHD): prevention of attacks of an angina of exertion.
Chronic heart failure (as a part of a combination therapy).

Route of administration and doses:

БИНЕЛОЛ® it is necessary to accept inside at the same time days irrespective of meal, without chewing and washing down with enough liquid.
Arterial hypertension and coronary heart disease
The average daily dose for treatment of arterial hypertension and coronary heart disease makes 2,5 - 5 mg (1/2 tablets on 5 mg - 1 tablet) 1 time a day. Use of drug in monotherapy or as a part of a combination therapy is possible.
At patients with a renal failure, and also at patients 65 years an initial dose are aged more senior makes 2,5 mg/days (1/2 tablets on 5 mg).
If necessary it is possible to increase a daily dose to 10 mg (2 tablets on 5 mg in one step).
Chronic heart failure
Treatment of chronic heart failure has to begin with gradual increase in a dose up to achievement of an individual optimum maintenance dose.
Selection of a dose in an initiation of treatment needs to be carried out according to the following scheme, maintaining week intervals and based on portability of this dose the patient: the dose making 1,25 mg of the drug BINELOL® (1/4 tablets on 5 mg) 1 time a day, can be increased at first to 2,5 - 5 mg of the drug BINELOL® (1/2 tablets on 5 mg - 1 tablet), and then - to 10 mg (2 tablets on 5 mg) 1 time a day.

Features of use:

Cancellation of beta adrenoblockers should be carried out gradually, within 10 days (up to 2 weeks at patients with coronary heart disease).
Control of the ABP and ChSS at the beginning of administration of drug has to be daily.
At elderly patients control of function of kidneys is necessary (1 time in 4-5 months).
At an angina of exertion the dose of drug has to provide ChSS at rest within 55-60 уд. / min., at loading - no more than 110 уд. / min.
Beta adrenoblockers can cause bradycardia: the dose should be lowered if ChSS less than 50-55 уд. / min. (see the section of the CONTRAINDICATION).
At the solution of a question of purpose of the drug BINELOL® patients should correlate to psoriasis carefully estimated advantage of use of drug and possible risk of an exacerbation of psoriasis.
The patients using 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.
Nebivolol does not influence glucose level at patients with a diabetes mellitus. Nevertheless, it is necessary to be careful at treatment of these patients as БИНЕЛОЛ® can mask the certain symptoms of a hypoglycemia (for example, tachycardia) caused by use of hypoglycemic means.
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).
Beta adrenoblockers should be applied with care at patients with a chronic obstructive pulmonary disease as the bronchospasm can amplify.
Beta adrenoblockers can increase sensitivity to allergens and weight of anaphylactic reactions.
Efficiency of beta adrenoblockers at smokers is lower, than at non-smoking patients.

Influence on ability of control of vehicles and mechanisms
Research works showed what небиволол does not exert impact on the speed of psychomotor reactions. To pilots of aircrew with soft degree of arterial hypertension (allowed to flight work) drug appoint 2,5 mg in an initial dose. Further (not earlier than in 2 weeks) at good tolerance of treatment and insufficient control of the ABP increase in a dose on 2,5 mg is possible. The recommended dose of-5 mg/days. Some patients can have side effects, most often dizziness, because of the lowered ABP. At emergence of similar effects the patient should not manage vehicles or to be engaged in potentially dangerous types of activity requiring special attention and speed and speed of psychomotor reactions. These effects arise most often right after an initiation of treatment or at increase in a dose.

Side effects:

From the central and peripheral nervous system: a headache, dizziness, increased fatigue, weakness, paresthesias (from 1% to 10%); seldom or never: a depression, decline in the ability to concentration of attention, drowsiness, sleeplessness, "dreadful" dreams, hallucinations, psychosis, spasms.
From digestive tract: nausea, a lock, a meteorism, diarrhea, dryness in a mouth (more than 1%).
From cardiovascular system: bradycardia, an acute heart failure, AV blockade, orthostatic hypotension, an exacerbation of the "alternating" lameness, short wind; seldom or never: disturbances of a heart rhythm, Reynaud's syndrome, peripheral hypostases, cardialgias.
Allergic reactions: skin itch, rash of erythematic character.
Others: a bronchospasm (including in the absence of obstructive diseases of lungs in the anamnesis), a photodermatosis, a hyperhidrosis, rhinitis, an aggravation of a course of psoriasis, a vision disorder, a xerophthalmus.

Interaction with other medicines:

At simultaneous use of beta adrenoblockers with the blockers of "slow" calcium channels (BSCC) (verapamil and diltiazem) the negative effect on contractility of a myocardium and AV conductivity amplifies. Contraindicated in/in administration of verapamil against the background of reception of a nebivolol. At a combination to antihypertensives, nitroglycerine or BMKK the expressed arterial hypotension can develop (extra care is necessary at a combination to Prazozinum).
At simultaneous use with antiarrhytmic means of the I class and with Amiodaronum strengthening of negative inotropic effect and lengthening of time of carrying out excitement on auricles is possible.
At simultaneous use of a nebivolol with cardiac glycosides strengthening of influence on delay of AV of conductivity is not revealed.
Simultaneous use of a nebivolol and drugs for the general anesthesia can cause suppression of reflex tachycardia and increase risk of development of arterial hypotension.
Clinically significant interaction of a nebivolol and non-steroidal anti-inflammatory drugs (NPVP) it is not established. Acetylsalicylic acid as antiagregantny means can be applied along with nebivololy.
Simultaneous use of tricyclic antidepressants, barbiturates and derivatives of a fenotiazin can strengthen hypotensive action of a nebivolol.
Pharmacokinetic interaction
At simultaneous use with the drugs inhibiting the return serotonin reuptake or other means which are biotransformed with participation of an isoenzyme of CYP2D6, metabolism of a nebivolol is slowed down.
At simultaneous use небиволол did not exert impact on pharmacokinetic parameters of digoxin.
At simultaneous use with Cimetidinum concentration of a nebivolol in a blood plasma increases (data on influence on pharmacological effects of drug are absent). Simultaneous use of ranitidine did not exert impact on pharmacokinetic parameters of a nebivolol.
At simultaneous use of a nebivolol with nikardipiny concentration of active agents in a blood plasma increased a little, however it has no clinical value.
The concomitant use of ethanol, furosemide or hydrochlorothiazide did not influence pharmacokinetics of a nebivolol.
It is not established clinically significant interaction of a nebivolol and warfarin. At simultaneous use sympathomimetic means suppress activity of a nebivolol.

Contraindications:

- hypersensitivity to a nebivolol or one of drug components.
- the expressed abnormal liver functions,
- acute heart failure,
- chronic heart failure in a decompensation stage (demanding intravenous administration of the drugs possessing an inotropic effect),
- cardiogenic shock,
- a sick sinus syndrome, including a sinoauricular block,
- atrioventricular (AV) blockade of II and III degrees (without artificial pacemaker),
- bronchospasm and bronchial asthma,
- not treated pheochromocytoma,
- depression,
- metabolic acidosis,
- the expressed bradycardia (ChSS less than 50 уд. / min.),
- the expressed arterial hypotension (systolic the ABP less than 90 mm hg),
serious obliterating illness of peripheral vessels (the "alternating" lameness, Reynaud's syndrome),
- myasthenia,
- age up to 18 years,
- lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

With care
- at a renal failure,
- at a diabetes mellitus,
- at hyperfunction of a thyroid gland,
- at allergic diseases in the anamnesis,
- at psoriasis.
- at an atrioventricular block of the I degree,
- at Printsmetal's stenocardia,
- at the chronic obstructive pulmonary disease (COPD),
- at patients 65 years are more senior.

Pregnancy and period of a lactation
At pregnancy drug is appointed only according to strict indications when the advantage for mother exceeds risk for a fruit (in connection with possible development in the newborn of bradycardia, arterial hypotension, a hypoglycemia and paralysis of breath). Treatment needs to be interrupted in 48-72 hours prior to childbirth. When it is impossible, it is necessary to provide strict observation of the newborn within 48-72 hours after delivery.
Researches on animals showed what небиволол is excreted with breast milk. If use of drug in the period of a lactation is necessary, then breastfeeding needs to be stopped.

Overdose:

Symptoms: decrease in the ABP, nausea, vomiting, cyanosis, sinus bradycardia, AV blockade, bronchospasm, cardiogenic shock, loss of consciousness, coma, cardiac standstill.
Treatment: gastric lavage, reception of absorbent carbon. In case of the expressed decrease in the ABP it is necessary to give to the patient horizontal position with the raised legs, if necessary in/in administration of liquid and vazopressor; as the subsequent measures purpose of 1-10 mg of a glucagon is possible. At bradycardia enter into 0,5-2 mg of atropine, in the absence of positive effect statement of a transvenous or endocardiac electrostimulator is possible. At AV it is recommended to blockade (Art. II-1II) in/in introduction beta адреностимуляторов. at their inefficiency it is necessary to consider a question of statement of an artificial pacemaker. At heart failure treatment is begun with administration of cardiac glycosides and diuretics, in the absence of effect introduction of a dopamine, Dobutaminum or vazodilatator is reasonable. At a bronchospasm appoint in/in beta2-adrenoceptors. At ventricular premature ventricular contraction - lidocaine (it is impossible to enter antiarrhytmic means of the class IA). At spasms - in/in diazepam.

Storage conditions:

List B.
At a temperature not above 30 °C.
To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Tablets of 5 mg.
On 14 tablets in PVH/PE/PVDH//the blister Is scarlet. 1 or 2 blisters together with the application instruction place in a cardboard pack.