Binelol, tablets 5 mg 28 pcs.

Binelolol has antiarrhythmic, hypotensive, antianginal action.

Pharmacodynamics

Nebivololol is a lipophilic, cardioselective β1-adrenoblocker of the third generation with vasodilatory properties. It has hypotensive, antianginal and antiarrhythmic effects. It reduces elevated BP at rest, under physical stress and stress. Competitively and selectively blocks synaptic and postsynaptic β1-adrenoreceptors, making them unavailable for catecholamines, modulates the release of endothelial vasodilatory factor – nitric oxide (NO).

Nebivololol is a racemate consisting of two enantiomers: SRRR-nebivolol (D-nebivolol) and RSSS-nebivolol (L-nebivolol) combining two pharmacological actions:

– D-nebivololol is a competitive and highly selective blocker of β1-adrenoreceptors (affinity for β1-adrenoreceptors is 293 times higher than for β2-adrenoreceptors);

– L-nebivololol has a mild vasodilator effect by modulating the release of relaxing factor (NO) from the vascular endothelium.

Hypotensive effect develops on the 2nd-5th day of treatment, a stable effect is noted after 1 month. Antihypertensive effect is maintained 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 changes in plasma renin activity).

The use of nebivololol improves indices of systemic and intracardiac hemodynamics. Nebivolol reduces HR and BP at rest and at exercise, decreases left ventricular end-diastolic pressure, decreases PEEP, improves diastolic heart function (decreases filling pressure), and increases ejection fraction.

Limiting myocardial oxygen demand (reduced HR, reduced preload and postload), reduces the number and severity of angina attacks and increases exercise tolerance.

The antiarrhythmic action is due to the suppression of pathological automatism of the heart (including in the pathological focus) and the slowing of AV conduction.

Pharmacokinetics

Intake. After oral administration, nebivolol is rapidly absorbed from the gastrointestinal tract. Food intake does not affect absorption, so nebivololol can be taken regardless of meals. Bioavailability is on average 12% in patients with fast metabolism and is almost complete in patients with slow metabolism. The efficacy of nebivolol does not depend on the metabolic rate.

Distribution. Plasma clearance in most patients (with fast metabolism) is reached within 24 h, and for hydroxymetabolites – after several days. Plasma concentrations (1-30 µg/L) are proportional to the dose.

The binding to plasma proteins (predominantly to albumin) for D-nebivololol is 98.1% and for L-nebivolol is 97.9%.

Metabolism. Nebivolol is actively metabolized, partially with the formation of active hydroxymetabolites. The rate of metabolism of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the CYP2D6 isoenzyme.

Evacuation. One week after administration, 38% (the amount of unchanged active ingredient is less than 0.5%) of the dose is excreted by the kidneys and 48% through the intestine.

In patients with fast metabolism the T1/2 values of enantiomers of nebivololol from plasma are on average 10 h. In patients with “slow” metabolism these values are 3-5 times higher.

In patients with fast metabolism the T1/2 values of hydroxymetabolites of both enantiomers from plasma averaged 24 hours; in patients with slow metabolism these values are approximately 2-fold increased.

The pharmacokinetics of nebivololol are not affected by the age and sex of patients.

Indications

Active ingredient

Composition

1 tablet contains:

active ingredient:

nebivololol (in the form of nebivololol hydrochloride) 5 mg,

excipients:

lactose monohydrate;

crospovidone (type A);

poloxamer 188;

povidone K30;

MC;

Magnesium stearate

How to take, the dosage

Overly, at the same time of day, regardless of meals, without chewing and with plenty of liquid.

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

In patients with renal insufficiency and in patients over 65 years of age, the initial dose is 2.5 mg/day (1/2 tablet of 5 mg).

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

Cronic heart failure. Treatment of chronic heart failure should begin with a gradual increase in dose until an individual optimal maintenance dose is reached.

The dose at the beginning of treatment should be adjusted as follows, at weekly intervals and based on the patient’s tolerance of this dose: a dose of 1.25 mg (1/4 tablet) once daily may be increased first to 2.5-5 mg (1/2-1 tablet) and then to 10 mg (2 tablets) once daily.

Interaction

Concomitant use of β-adreno-blockers with BMCCs (verapamil and diltiazem) increases adverse effects on myocardial contractility and AV conduction. IV administration of verapamil during nebivolol administration is contraindicated. Severe arterial hypotension may develop if combined with hypotensive agents, nitroglycerin or BMCCs (special caution is required when combined with prazosin).

Concomitant use with class I antiarrhythmic agents and amiodarone may increase the negative inotropic effect and prolongation of the excitation time through the atria.

In concomitant use of nebivololol with cardiac glycosides no increased effect on delayed AV conduction has been found.

The concomitant use of nebivololol and drugs for general anesthesia may inhibit reflex tachycardia and increase the risk of arterial hypotension.

Clinically significant interaction of nebivololol and NSAIDs has not been established. Acetylsalicylic acid as an antiplatelet agent can be used concomitantly with nebivololol.

The concomitant use of tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the hypotensive effect of nebivololol.

Pharmacokinetic interaction

When used concomitantly with drugs that inhibit serotonin reuptake or other agents biotransforming with participation of CYP2D6 isoenzyme, metabolism of nebivolol is slowed.

When used concomitantly, nebivololol had no effect on the pharmacokinetic parameters of digoxin.

Concomitant use with cimetidine increases plasma concentrations of nebivololol (data on the effect on the pharmacological effects of the drug are not available). Concomitant use of ranitidine had no effect on the pharmacokinetic parameters of nebivololol.

Concomitant use of nebivololol with nicardipine slightly increases plasma concentrations of the active substances, but this has no clinical significance.

The concomitant use of ethanol, furosemide or hydrochlorothiazide has no effect on the pharmacokinetics of nebivololol.

No clinically significant interaction of nebivololol and warfarin has been established.

In concomitant use, sympathomimetic agents inhibit the activity of nebivololol.

Special Instructions

The withdrawal of β-adrenoblockers should be gradual, over 10 days (up to 2 weeks in patients with CHD).

The monitoring of BP and HR at the beginning of drug administration should be daily.

In elderly patients, renal function should be monitored (once every 4-5 months).

In angina pectoris, the drug dose should provide a resting HR of 55-60 beats/minute, and not more than 110 beats/minute on exertion.

The β-adrenoblockers can cause bradycardia: the dose should be reduced if the HR is less than 50-55 beats/minute.

When deciding whether to prescribe Binelol in patients with psoriasis, the anticipated benefit of the drug must be carefully weighed against the possible risk of psoriasis exacerbation.

Patients who wear contact lenses should be aware that the use of β-adrenoblockers may decrease tear fluid production.

In surgical procedures, the anesthesiologist should be advised that the patient is taking β-adrenoblockers.

Nebivololol has no effect on glucose levels in patients with diabetes mellitus. However, caution should be exercised when treating these patients because Binelolol may mask certain symptoms of hypoglycemia (e.g., tachycardia) caused by the use of hypoglycemic agents.

Plasma glucose monitoring should be performed once every 4-5 months (in diabetic patients).

β-adrenoblockers should be used with caution in patients with COPD because bronchospasm may increase.

The β-adrenoblockers may increase allergen sensitivity and the severity of anaphylactic reactions.

The effectiveness of β-adrenoblockers is lower in smokers than in nonsmokers.

The effect on the ability to drive a car or perform tasks that require increased speed of physical and mental reactions. Research studies have shown that nebivolol has no effect on the speed of psychomotor reactions. Pilots of flight personnel with mild degree of arterial hypertension, admitted to the flight work, shall be prescribed the drug in an initial dose of 2.5 mg. Further (not earlier than in 2 weeks) in case of good tolerance of treatment and insufficient BP control it is possible to increase the dose by 2.5 mg. The recommended dose is 5 mg/day. Some patients may experience side effects, most commonly dizziness, due to low blood pressure. If such effects occur, the patient should not drive vehicles or engage in potentially dangerous activities requiring special attention and quick psychomotor reactions. These effects usually occur immediately after the start of treatment or when increasing the dose.

Contraindications

Side effects

CNS and peripheral nervous system disorders: headache, dizziness, increased fatigue, weakness, paresthesias (1 to 10%); in very rare cases – depression, reduced ability to concentrate, drowsiness, insomnia, nightmares, hallucinations, psychosis, seizures.

Gastrointestinal disorders: nausea, constipation, flatulence, diarrhea, dry mouth (more than 1%).

Systemic diseases: bradycardia, acute heart failure, AV blockade, orthostatic hypotension, worsening of intermittent claudication, dyspnea; in very rare cases – cardiac arrhythmia, Raynaud’s syndrome, peripheral edema, cardialgia.

Allergic reactions: skin itching, erythematous rash.

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

Overdose

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

treatment: gastric lavage, administration of activated charcoal. If BP is significantly decreased, the patient should be placed in a horizontal position with elevated legs, if necessary, intravenous administration of fluids and vasopressors; 1-10 mg of glucagon may be given as a follow-up. In bradycardia, 0.5-2 mg of atropine is administered intravenously; if there is no positive effect, a transvenous or intracardiac pacemaker may be placed. For AV block of II-III degree, intravenous injection of β-adrenostimulators is recommended, and if they are ineffective, the placement of an artificial pacemaker should be considered. In cardiac insufficiency, treatment shall be started with introduction of cardiac glycosides and diuretics, in the absence of effect it is advisable to introduce dopamine, dobutamine or vasodilators. In bronchospasm, intravenous β-adrenomimetics are prescribed. For ventricular extrasystole, lidocaine (class IA antiarrhythmic agents should not be administered). For seizures, intravenous diazepam.

Pregnancy use

In pregnancy, Binelol is prescribed only under strict indications, when the benefit to the mother exceeds the risk to the fetus (due to possible development of bradycardia, arterial hypotension, hypoglycemia and respiratory paralysis in the newborn). Treatment should be stopped 48-72 hours before delivery.

In cases where this is not possible, strict observation of the newborn for 48-72 hours after delivery should be ensured.

An animal study has shown that nebivololol is excreted with breast milk. If the use of the drug during lactation is necessary, breastfeeding should be stopped.

Similarities