Nebilet, pills 5mg, 28pcs

Composition

Active ingredients:

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

Auxiliary substances:

lactose monohydrate-141.75 mg,

corn starch-46 mg,

sodium croscarmellose-13.8 mg,

hypromellose 15 MPa×s-4.6 mg,

polysorbate 80-0.46 mg,

microcrystalline cellulose-16.1 mg,

colloidal silicon dioxide-0.69 mg,

magnesium stearate-1.15 mg

Pharmacological action

Pharmacodynamics

Cardioselective beta-1-adrenoblocker. It has antihypertensive, antianginal and antiarrhythmic effects. Reduces elevated blood pressure at rest, during physical exertion and stress. Competitively and selectively blocks postsynaptic β1-adrenergic receptors, making them inaccessible to catecholamines, modulates the release of endothelial vasodilating factor nitric oxide (NO).

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

— D-nebivolol is a competitive and highly selective blocker of β1-adrenergic receptors—

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

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

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

Reducing the need for myocardial oxygen (reducing heart rate and reducing preload and afterload), reduces the number and severity of angina attacks and increases exercise tolerance.

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

Pharmacokinetics

Suction

After oral use, both enantiomers are rapidly absorbed. Food intake does not affect absorption, so nebivolol can be taken regardless of food intake. The bioavailability of nebivolol after oral use is on average 12% in individuals with a “fast” metabolism (first-pass effect through the liver) and is almost complete in individuals with a “slow” metabolism.

Distribution

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

Metabolism

It is metabolized by acyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and are excreted as O-and N-glucuronides.

Deduction

It is excreted by the kidneys (38%) and through the intestines (48%). In individuals with “fast” metabolism of T1 / 2 hydroxymetabolites-24 hours, nebivolol enantiomers-10 hours; in individuals with “slow” metabolism: hydroxymetabolites-48 hours, nebivolol enantiomers-30-50 hours.

Excretion of unchanged nebivolol in the urine is less than 0.5% of the amount of the drug taken orally.

Indications

Ischemic heart disease: prevention of tension-type angina attacks; arterial hypertension; chronic heart failure (as part of combination therapy).

Use during pregnancy and lactation

Nebivolol is excreted in breast milk. If it is necessary to take Nebilet® during lactation, breast-feeding should be discontinued.

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

Treatment should be interrupted 48-72 hours before delivery. In cases where this is not possible, it is necessary to establish strict monitoring of newborns within 48-72 hours after delivery.

Contraindications

– Hypersensitivity to nebivolol or one of the components of the drug;

– chronic heart failure in the stage of decompensation (requiring I/V use of drugs with inotropic action);

acute heart failure;

– SSSU, including sinoatrial blockade;

– AV-block II and III degree (without artificial pacemaker);

– severe hypotension (systolic BP less than 90 mm Hg. St. )

-cardiogenic shock;

– pheochromocytoma (without the simultaneous use of alpha-blockers);

metabolic acidosis;

– myasthenia gravis;

– pronounced violations of the liver;

– bradycardia (heart rate less than 60 beats/min);

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

– bronchospasm and bronchial asthma history; 

– depression;

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

– children and adolescents under 18 years of age (efficacy and safety have not been studied).

The drug should be used cautiously:  

– with renal failure,

– diabetes mellitus,

– hyperthyroidism,

– a history of allergic diseases,

– psoriasis,

– chronic obstructive pulmonary disease, A

-V block of the first degree,

– Prinzmetal angina pectoris,

– patients over the age of 75 years.

Side effects

the Frequency of side effects: uncommon ( > 0.1% and < 1%); often ( > 10%); often ( > 1% and < 10%); very rare ( < To 0.01%, including private messages); rarely ( > 0.01% and < 0,1%). From the cardiovascular system: infrequently-bradycardia, acute heart failure, AV block, orthostatic hypotension, Raynaud’s syndrome. From the central nervous system and peripheral nervous system: often-headache, dizziness, fatigue, weakness, paresthesia; infrequently-depression, nightmares, confusion; very rarely-fainting, hallucinations. From the skin and subcutaneous tissues: infrequently-erythematous skin rash, pruritus; very rarely-aggravation of the course of psoriasis; in some cases-angioedema. From the digestive system: often – nausea, constipation, diarrhea; infrequently-dyspepsia, flatulence, vomiting. Other: infrequently-bronchospasm; rarely-dry eyes.

Interaction

Pharmacokinetic interaction

Concomitant use of nebivolol with drugs that inhibit serotonin reuptake or other agents that biotransform with the participation of the CYP2D6 isoenzyme increases the concentration of nebivolol in blood plasma, the metabolism of nebivolol slows down, which may lead to the risk of bradycardia. When used concomitantly with digoxin, nebivolol has no effect on the pharmacokinetic parameters of digoxin. When nebivolol is co-administered with cimetidine, the concentration of nebivolol in the blood plasma increases. Concomitant use of nebivolol and ranitidine does not affect the pharmacokinetic parameters of nebivolol. When nebivolol is co-administered with nicardipine, the concentration of active substances in the blood plasma increases slightly, but this is not of clinical significance. Concomitant use of nebivolol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol. There was no clinically significant interaction between nebivolol and warfarin. Concomitant use of nebivolol with insulin and oral hypoglycemic agents may mask the symptoms of hypoglycemia (tachycardia). Pharmacodynamic interaction concomitant use of beta-blockers with slow calcium channel blockers (verapamil and diltiazem) increases the negative effect on myocardial contractility and AV conduction. Intravenous use of verapamil with nebivolol is contraindicated. Concomitant use of nebivolol with antihypertensive agents, nitroglycerin or slow calcium channel blockers may result in severe hypotension (special caution is necessary when combined with prazosin). Concomitant use of nebivolol with Class I antiarrhythmic drugs and amiodarone may increase the negative inotropic effect and prolong the time of atrial excitation. When nebivolol was co-administered with cardiac glycosides, there was no increase in the effect on slowing AV conduction. Concomitant use of nebivolol and general anaesthetic agents may cause suppression of reflex tachycardia and increase the risk of hypotension. There is no clinically significant interaction between nebivolol and NSAIDs. Concomitant use of nebivolol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the hypotensive effect of nebivolol.

How to take it, course of use and dosage

Tablets are taken orally,1 time / day, preferably always at the same time of day, regardless of food intake, with a sufficient amount of liquid.

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

In patients with renal insufficiency, as well as in patients over the age of 65 years, the recommended initial dose is 2.5 mg (1/2 tab. )/day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tablets of 5 mg in 1 reception).

Treatment of chronic heart failure should begin with a slow increase in the dose until the individual optimal maintenance dose is reached.

Dose selection at the beginning of treatment should be carried out according to the following scheme, maintaining intervals from 1 to 2 weeks and based on the patient’s tolerance to this dose: the dose of 1.25 mg nebivolol (1/4 tab. 5 mg) 1 time/day can be increased first to 2.5-5 mg (1/2 tab. 5 mg or 1 tab. 5 mg), and then to 10 mg (2 tab. 5 mg) 1 time/day.

The maximum daily dose is 10 mg 1 time/day.

At the beginning of treatment and with each dose increase, the patient should be under medical supervision for at least 2 hours to ensure that the clinical condition remains stable (especially, blood pressure, heart rate, conduction disorders, as well as symptoms of exacerbation of the course of chronic heart failure).

Rules for dividing tablets

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

Overdose

Symptoms: marked decrease in blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, AV block, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest.

Treatment: gastric lavage, taking activated charcoal. In case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, intravenous use of fluid and vasopressors.

With bradycardia,0.5-2 mg of atropine should be administered intravenously in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be installed.

In case of AV block (grade II-III), intravenous use of beta-adrenostimulants is recommended; if they are ineffective, an artificial pacemaker should be considered.

In case of heart failure, treatment begins with the introduction of cardiac glycosides and diuretics, if there is no effect, it is advisable to introduce dopamine, dobutamine or vasodilators.

In case of bronchospasm, intravenous beta-2-adrenergic stimulants are used.

For ventricular estrasystole – lidocaine (class IA antiarrhythmics cannot be administered).

Special instructions

Beta-blockers should be discontinued gradually over 10 days (up to 2 weeks in patients with CHD). Monitoring of blood pressure and heart rate at the beginning of taking the drug should be daily. In elderly patients, monitoring of renal function is necessary (1 time in 4-5 months). With angina pectoris, the dose of the drug should provide a resting heart rate in the range of 55-60 beats / min, with a load of no more than 110 beats / min. Beta-blockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats / min. When deciding whether to use Nebilet® in patients with psoriasis, the expected benefit of using the drug and the possible risk of exacerbation of psoriasis should be carefully correlated. Patients who use contact lenses should take into account that the use of beta-blockers may reduce the production of tear fluid. When performing surgical procedures, the anesthesiologist should be warned that the patient is taking beta-blockers. Nebivolol does not affect the plasma glucose concentration in patients with diabetes mellitus. However, caution should be exercised when treating these patients, as Nebilet® may mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic agents for oral use and insulin. Monitoring of glucose concentration in blood plasma should be carried out once every 4-5 months (in patients with diabetes mellitus). When the thyroid gland is hyperfunctional, beta-blockers can mask tachycardia. Beta-blockers should be used with caution in patients with chronic obstructive pulmonary disease, as bronchospasm may increase. Beta-blockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Effect on the ability to drive vehicles and other mechanisms requiring increased concentration of attentionthe effect of Nebilet® the ability to drive vehicles and manage mechanisms was not specifically studied. Nebivolol pharmacodynamic studies have shown that Nebilet has no effect on psychomotor function. During treatment with Nebilet® (if side effects occur), caution should be exercised when driving vehicles and when engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets

Storage conditions

Keep out of reach of children at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Nebivolol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, Nursing mothers as prescribed by a doctor, Pregnant women as prescribed by a doctor

Indications

Heart Failure, Hypertension, Angina, Arrhythmia