Nebilet, tablets 5 mg 28 pcs

Pharmacodynamics

A cardioselective beta 1-adrenoblocker. It has hypotensive, antianginal and antiarrhythmic effects. Reduces elevated BP at rest, under physical stress and stress. Competitively and selectively blocks postsynaptic β1-adrenoreceptors, making them unavailable for catecholamines, modulates the release of endothelial vasodilatory factor nitric oxide (NO).

Nebivololol is a racemate 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;

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

The hypotensive effect is also due to decrease of renin-angiotensin-aldosterone system (RAAS) activity (does not directly correlate with changes in plasma renin activity).

Sustained hypotensive effect develops after 1-2 weeks of regular use of the drug, and in some cases – after 4 weeks, a stable effect is noted after 1-2 months.

Limiting myocardial oxygen demand (decrease in HR and decrease in ante- and post-load), it 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

absorption

After oral administration, both enantiomers are rapidly absorbed. Food intake has no effect on absorption, so nebivolol can be taken regardless of meals. The bioavailability of nebivolol after oral administration averages 12% in those with “fast” metabolism (first-pass effect through the liver) and is almost complete in those with “slow” metabolism.

Distribution

In plasma both enantiomers are predominantly bound to albumin. Binding to plasma proteins is 98.1% for D-nebivololol and 97.9% for L-nebivololol.

Metabolism

Metabolized by acyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy- and amino derivatives conjugate with glucuronic acid and are excreted as O- and N-glucuronides.

Elimination

Extracted by the kidneys (38%) and through the intestine (48%). In persons with “fast” metabolism T1/2 of hydroxymetabolites is 24 h, enantiomers of nebivololol – 10 h; in persons with “slow” metabolism: hydroxymetabolites – 48 h, enantiomers of nebivololol – 30-50 h.

The urinary excretion of unchanged nebivololol is less than 0.5% of the amount of the drug taken orally.

Indications

Ischemic heart disease: prevention of angina attacks; arterial hypertension; chronic heart failure (in combination therapy).

Active ingredient

Composition

Active substances:

Nebivololol hydrochloride micronized 5.45 mg, which corresponds to the content of nebivolol 5 mg.

Associates:

Lactose monohydrate – 141.75 mg,

Corn starch – 46 mg,

How to take, the dosage

The tablets are taken orally, once a day, preferably always at the same time of the day, regardless of meals, with plenty of fluids.

The average daily dose for the treatment of arterial hypertension and CHD is 2.5-5 mg (1/2-1 tablet). Nebilet® can be used in monotherapy or in combination with other BP-lowering agents.

In patients with renal impairment and in patients over 65 years of age, the recommended starting dose is 2.5 mg (1/2 tablet)/day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tablets of 5 mg at 1 sitting).

The treatment of chronic heart failure should begin with slowly increasing the dose until an individual optimal maintenance dose is reached.

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

The maximum daily dose is 10 mg once daily.

The patient should be monitored for at least 2 hours at the start of treatment and each time the dose is increased to make sure that the clinical condition remains stable (especially BP, HR, conduction disturbances, and symptoms of worsening course of chronic heart failure).

Rules for dividing tablets

To divide, place the tablet on a hard, flat surface with the crosshair notch facing up, press down on the tablet with both index fingers. To get 1/4 tablet, repeat the same steps with 1/2 tablet.

Interaction

Pharmacokinetic interaction

. Concomitant use of nebivololol with drugs that inhibit serotonin reuptake, or other agents biotransformed with the participation of CYP2D6 isoenzyme, increases the plasma concentration of nebivolol, nebivolol metabolism is slowed, which may lead to a risk of bradycardia.

Special Instructions

Contraindications

– Hypersensitivity to nebivololol or one of the drug components;

– Chronic heart failure in decompensation (requiring intravenous administration of drugs with inotropic action);

p> – acute heart failure;

– CAD, including sinoatrial block;

– AV blockade of II and III degree (without pacemaker);

– significant arterial hypotension (systolic BP less than 90 mm Hg).Hg).);

– cardiogenic shock;

– pheochromocytoma (without concomitant use of alpha-adrenoblockers);

– metabolic acidosis;

– myasthenia gravis;

– significant liver dysfunction;

– bradycardia (HR less than 60 beats/min.

– severe peripheral vascular occlusive disease (intermittent claudication, Raynaud’s syndrome);

– history of bronchospasm and bronchial asthma;

– depression;

– lactose intolerance, lactase deficiency, and glucose/galactose malabsorption syndrome;

– childhood and adolescence under 18 years (effectiveness and safety not studied).

Cautious use of the drug:

– in renal insufficiency,

– diabetes mellitus,

– Thyroid hyperfunction,

– A history of allergic conditions,

p> – psoriasis,

– chronic obstructive pulmonary disease, A

– Grade I V-blockade,

– Prinzmetal angina,

– patients over 75 years of age.

Side effects

Overdose

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

Treatment: Gastric lavage, administration of activated charcoal. In case of pronounced BP decrease, the patient should be placed in a horizontal position with elevated legs, if necessary, IV fluids and vasopressors should be administered.

In case of bradycardia, 0.5-2 mg of atropine should be administered by IV, if there is no positive effect, transvenous or intracardiac pacemaker can be placed.

In AV-blockade (stage II-III) it is recommended to administer beta-adrenostimulants by IV, and if they are ineffective, an artificial pacemaker should be considered.

In case of heart failure, treatment begins with administration of cardiac glycosides and diuretics; if there is no effect, dopamine, dobutamine or vasodilators are appropriate.

In case of bronchospasm, intravenous β2-adrenoreceptor stimulants are used.

In case of ventricular estrasystole, lidocaine (Class IA antiarrhythmic agents should not be administered).

Pregnancy use

Nebivolol is excreted with the breast milk. If Nebilet® must be taken during lactation, breastfeeding must be stopped.

In pregnancy Nebilet® is administered only with vital indications when the benefit for the mother exceeds the possible risk for the fetus or newborn (due to possible development of bradycardia, arterial hypotension and hypoglycemia in fetus and newborn). If Nebilet® treatment is necessary the uteroplacental blood flow and fetal growth should be monitored.

The treatment should be discontinued 48-72 h before delivery. In cases where this is not possible, strict neonatal monitoring should be established for 48-72 h after delivery.

Similarities