Binelol - instructions for use, doses, side effects, contraindications

One tablet contains active stuffthe: nebivolol (in the form of a nebivolol guidelt; / RTI & gt; Excipientslactose monohydrate 85.96 mg, crospovidone (type A) 6.89 mg, poloxamer188 6.90 mg, povidone K-30 3.50 mg, microcrystalline cellulose 119.00 mg, magnesium stearate 2, 30 mg.

Description:Round, biconvex tablets are white, with a cross-shaped notch on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a lipophilic, cardioselective beta-adrenoblocker of the third generation with vasodilating properties. Has antihypertensive, anti-anginal and antiarrhythmic effect. Reduces elevated blood pressure (BP) at rest, with physical stress and stress. Competitively and selectively blocks synaptic and postsynaptic β1-adrenergic receptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide (NO).

Nebivolol is a racemate consisting of two enantiomers: SRRR-nebivolol (Dnebivolol) and RSSS-nebivolol (LNebivolol), combining two pharmacological actions:

- DNebivolol is a competitive and highly selective beta blocker₁-adrenoceptors (affinity for b₁-adrenoceptors 293 times higher than to b₂-adrenergic receptors).

- L- Nebivolol has a mild vasodilating effect due to the modulation of the release of the relaxing factor (NO) from the vascular endothelium.

The hypotensive effect develops on the 2nd-5th day of treatment, stable effect is observed after 1 month. Antihypertensive effect persists with long-term treatment. The hypotensive effect is also due to a decrease in the activity of the renin-angiotensin system (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 heart rate and heart rate at rest and under physical exertion, 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, reducing preload and afterload), reduces the number and severity of angina attacks and increases the tolerance of exercise.

Antiarrhythmic effect is due to suppression of pathological automatism of the heart (including in the pathological focus) and slowing down AV conductivity.

Pharmacokinetics:

Suction

After oral administration nebivolol quickly absorbed from the gastrointestinal tract. Eating does not affect absorption, 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.

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%, and for L- nebivolol - 97.9%.

Metabolism

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.

Excretion

One week 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% - through the intestines.

In patients with "fast" metabolism, the values of the half-life (T_1/2) enantiomers of nebivolol from the blood plasma averagely 10 hours. In patients with a "slow" metabolism, these values increase 3-5 times.

In patients with "fast" metabolism, the T_1/2hydroxymetabolites of both enantiomers from blood plasma averagely 24 hours, in patients with a "slow" metabolism these values are approximately 2-fold increased.

The pharmacokinetics of nebivolol is not affected by age and sex of patients.

Indications:

- Arterial hypertension;

- Coronary heart disease (IHD): prevention of angina pectoris attacks.

- Chronic heart failure (as part of combination therapy).

Contraindications:

- increased sensitivity to nebivolol or one of the components of the drug,

- expressed violations of the liver,

- acute heart failure,

- chronic heart failure in the stage of decompensation (requiring intravenous administration of drugs with an inotropic effect),

- cardiogenic shock,

- syndrome of weakness of the sinus node, including sinoauric blockade,

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

- bronchospasm and bronchial asthma,

- an untreated pheochromocytoma,

- depression,

- metabolic acidosis,

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

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

- severe obliterating diseases of peripheral vessels ("intermittent" lameness, Raynaud's syndrome),

- myasthenia gravis,

- age to 18 years,

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

- with renal failure,

- with diabetes mellitus,

- with hyperfunction of the thyroid gland,

- with allergic diseases in the anamnesis,

- with psoriasis,

- with atrioventricular blockade of the first degree,

- with angina of Prinzmetal,

- in chronic obstructive pulmonary disease (COPD),

- in patients older than 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 delivery. In cases where this is not possible, it is necessary to ensure strict observation of the newborn within 48-72 hours after delivery.

Studies in animals have shown that nebivolol excreted in breast milk. If the drug is used during lactation, breastfeeding should be discontinued.

Dosing and Administration:

BINELOL ® 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.

Arterial hypertension and ischemic heart disease

The average daily dose for treatment of arterial hypertension and coronary heart disease is 2.5 - 5 mg (1/2 tablets of 5 mg - 1 tablet) once a day.It is possible to use the drug in monotherapy or as part of a combination therapy.

In patients with renal insufficiency, as well as in patients older than 65 years, the initial dose is 2.5 mg / day. (1/2 tablets of 5 mg each).

If necessary, the daily dose can be increased to 10 mg (2 tablets of 5 mg at a time).

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 weekly intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg of BINELOL® (1/4 tablets of 5 mg) once a day can be increased first up to 2.5 - 5 mg of BINELOL® (1/2 tablets of 5 mg - 1 tablet), and then - up to 10 mg (2 tablets of 5 mg) once a day.

Side effects:

From the central and peripheral nervous system: headache, dizziness, fatigue, weakness, paresthesia (from 1% to 10%); in very rare cases: depression, decreased ability to concentrate, drowsiness, insomnia, "nightmarish" dreams, hallucinations, psychosis, convulsions.

From the gastrointestinal tract: nausea, constipation, flatulence, diarrhea, dry mouth (more than 1%).

From the cardiovascular system: bradycardia, acute heart failure, AV blockade, orthostatic hypotension, aggravation of "intermittent" lameness, dyspnea; in very rare cases: heart rhythm disturbances, Raynaud's syndrome, peripheral edema, cardialgia.

Allergic reactions: skin itch, eruptive rash.

Other: bronchospasm (including in the absence of obstructive pulmonary disease in history), photodermatosis, hyperhidrosis, rhinitis, exacerbation of psoriasis, visual impairment, dry eyes.

Overdose:

Symptoms: decreased blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, AV blockade, bronchospasm, cardiogenic shock, loss of consciousness, coma, cardiac arrest.

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, with / injection of liquid and vasopressors; as a follow-up, the administration of 1-10 mg glucagon is possible. With bradycardia, intravenously injecting 0.5-2 mg of atropine, in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be administered. When AV blockade (II-III st.) is recommended iv injection of beta-adrenostimulyatorov, if their inefficiency should consider the issue of 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 appoint iv / beta₂-adrenoceptors. With ventricular extrasystole - lidocaine (antiarrhythmic drugs of class IA). With convulsions - in / in diazepam.

Interaction:

With simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) the negative effect on myocardial contractility and AV conductivity. 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).

When used simultaneously with antiarrhythmic agents of the first class and with amiodarone, it is possible to enhance the negative inotropic effect and elongation the time of excitation in the atria.

With the simultaneous use of nebivolol with cardiac glycosides, no increase in the effect on slowing AV conductivity.

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 interactions of nebivolol and non-steroidal anti-inflammatory drugs (NSAIDs) 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 can enhance the antihypertensive effect of nebivolol.

Pharmacokinetic interaction

When used simultaneously with drugs that inhibit serotonin reuptake, or other means, 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.

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.

Special instructions:

The abolition of beta-adrenoblockers should be carried out gradually, within 10 days (up to 2 weeks in patients with coronary 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 the range of 55-60 bpm, with a load of 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. (see section CONTRAINDICATIONS).

When deciding whether to prescribe BINELOL®, patients with psoriasis should carefully correlate the perceived benefits of using 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 interventions, an anesthesiologist should be warned that the patient is taking beta-blockers.

Nebivolol does not affect the level of glucose in patients with diabetes mellitus. Nevertheless, care should be taken in the treatment of these patients, since BINELOL® may mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents.

Control 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 chronic obstructive pulmonary disease, as bronchospasm may increase. 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.

Effect on the ability to drive transp. cf. and fur:

Research work has shown that nebivolol does not affect the speed of psychomotor reactions. Pilots aircrew with mild degrees of arterial hypertension (admitted to the flight operations) the drug administered 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 may increase the dose by 2.5 mg. The recommended dose is 5 mg / day. Some patients may experience side effects, most often dizziness, due to low blood pressure. If you experience such effects, the patient should not drive vehicles or to engage in potentially hazardous activities that require special attention and speed and quickness of psychomotor reactions. These effects occur most often immediately after the start of treatment or with increasing doses.

Form release / dosage:

Tablets 5 mg.

Packaging:For 14 tablets in PVC / PE / PVDC / / Al blister. 1, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

List B.

At a temperature of no higher than 30 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009000/09

Date of registration:09.11.2009 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Beluga, medicines and cosmetics.Beluga, medicines and cosmetics. Croatia

Manufacturer: & nbsp

BELUPO, Pharmaceuticals & Cosmetics, d.d. Croatia

Representation: & nbspBeluga, medicines and cosmetics. Beluga, medicines and cosmetics. Croatia

Information update date: & nbsp11.02.2017

Illustrated instructions

Instructions

Binelol® (Binelol®)