Nebilet tablets 5mg, No. 14

• arterial hypertension;

• ischemic heart disease: prevention of angina attacks;

• chronic heart failure (as part of combination therapy).

NebiletЃ tablets are taken orally, once a day, preferably at the same time, regardless of food intake, with a sufficient amount of liquid.

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

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

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

The selection of the dose at the beginning of treatment should be carried out according to the following scheme: while maintaining intervals from one to two weeks and focusing on the tolerance of this dose by the patient: a dose of 1.25 mg of NebiletЃ (1/4 of a 5 mg tablet) 1 time per day, can be increased first to 2.5 - 5 mg once a day of the drug NebiletЃ (1/2 tablet of 5 mg or 1 tablet), and then to 10 mg (2 tablets of 5 mg) once a day ...

The maximum daily dose is 10 mg once a day.

At the beginning of treatment and with each dose increase, the patient should be under medical supervision for at least 2 hours to make sure that the clinical condition remains stable (especially: blood pressure, heart rate, conduction disturbances, as well as symptoms of worsening chronic heart failure). To divide, place the tablet on a hard, flat surface with a cruciform notch up, press down on the tablet with both index fingers. For a quarter (1/4) tablet, repeat the same steps with half (1/2) tablet.

Active substance:

nebivolol hydrochloride micronized - 5.45 mg, equivalent of nebivolol - 5.00 mg

Excipients: lactose monohydrate, corn starch, croscarmellose sodium, hypromellose (viscosity 15 mPa * s), polysorbate-80, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

• hypersensitivity to the active substance or one of the components of the drug;

• acute heart failure;

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

• severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

• sick sinus syndrome, including sinus blockade;

• atrioventricular block II and III degree (without an artificial pacemaker);

• bradycardia (heart rate less than 60 beats / min.):

• cardiogenic shock;

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

• metabolic acidosis;

• severe liver dysfunction;

• history of bronchospasm and bronchial asthma;

• severe obliterating peripheral vascular disease ('intermittent' claudication, Raynaud's syndrome);

• myasthenia gravis;

• depression;

• lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;

• age up to 18 years (efficacy and safety in this age group have not been studied).

Carefully

• renal failure;

• diabetes;

• hyperfunction of the thyroid gland;

• history of allergic diseases, psoriasis;

• chronic obstructive pulmonary disease;

• atrioventricular block I degree;

• Prinzmetal's angina;

• over 75 years of age.

Trade name of the drug - NebiletЃ

International non-proprietary name:

- nebivolol

Dosage form:

pills

Composition:

for 1 tablet:

Active ingredient: micronized nebivolol hydrochloride - 5.45 mg, nebivolol equivalent - 5.00 mg

Excipients: lactose monohydrate, corn starch, croscarmellose sodium, hypromellose (viscosity 15 mPa * s), polysorbate-80, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

Description:

round biconvex tablets of almost white color with a cross-shaped notch for division.

Pharmacotherapeutic group:

? 1-adrenergic blocker selective

ATX code: —07ј¬12

Pharmacological properties:

Pharmacodynamics
Cardioselective? 1-blocker. Nebivolol has hypotensive, antianginal and antiarrhythmic effects. Reduces high blood pressure (BP) at rest, during physical exertion and stress. Competitively and selectively blocks postsynaptic ?1-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), which combines two pharmacological actions:

1. D-nebivolol is a competitive and highly selective ?1-adrenergic receptor blocker;

2. L-nebivolol has a mild vasodilator effect by modulating the release of vasodilating factor (NO) from the vascular endothelium.
   The antihypertensive effect is also due to a decrease in the activity of the renin-angiotensin-aldosterone system (RAAS) (does not directly correlate with changes in renin activity in the blood plasma).
   A stable hypotensive effect develops after 1-2 weeks of regular administration of the drug, and in some cases - after 4 weeks, a stable effect is observed after 1-2 months.
   By decreasing myocardial oxygen demand (decreased heart rate (HR), decreased preload and afterload), nebivolol reduces the number and severity of angina attacks and increases exercise tolerance. The antiarrhythmic effect is due to the suppression of the pathological automatism of the heart (including in the pathological focus) and the slowing down of atrioventricular conduction. Pharmacokinetics
   Absorption. After oral administration, both enantiomers are rapidly absorbed. Absorption is not affected by food intake, so nebivolol can be taken with or without food. The bioavailability of orally administered nebivolol averages 12% in patients with a 'fast' metabolism (a 'first pass' effect) and is almost complete in patients with a 'slow' metabolism.metabolism.
   Distribution. In blood plasma, both enantiomers are predominantly associated with albumin. Plasma protein binding is 98.1% for D-nebivolol and 97.9% for L-nebivolol.
   Excretion. Nebivolol is metabolized by alicyclic and aromatic hydroxylation, partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and excreted in the form of O- and N-glucuronides, by the kidneys (38%), through the intestine (48%). T1 / 2 in patients with a 'fast' metabolism: hydroxy metabolites - 24 hours, nebivolol enantiomers - 10 hours; in patients with 'slow' metabolism: hydroxymetabolites - 48 hours, nebivolol enantiomers - 30-50 hours. Excretion of unchanged nebivolol through the kidneys is less than 0.5% of the oral dose.

Indications for use:

• arterial hypertension;

• ischemic heart disease: prevention of angina attacks;

• chronic heart failure (as part of combination therapy).

Contraindications:

• hypersensitivity to the active substance or one of the components of the drug;

• acute heart failure;

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

• severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

• sick sinus syndrome, including sinus blockade;

• atrioventricular block II and III degree (without an artificial pacemaker);

• bradycardia (heart rate less than 60 beats / min.):

• cardiogenic shock;

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

• metabolic acidosis;

• severe liver dysfunction;

• history of bronchospasm and bronchial asthma;

• severe obliterating peripheral vascular disease ('intermittent' claudication, Raynaud's syndrome);

• myasthenia gravis;

• depression;

• lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;

• age up to 18 years (efficacy and safety in this age group have not been studied).

Carefully

• renal failure;

• diabetes;

• hyperfunction of the thyroid gland;

• history of allergic diseases, psoriasis;

• chronic obstructive pulmonary disease;

• atrioventricular block I degree;

• Prinzmetal's angina;

• over 75 years of age.

Pregnancy and breastfeeding

During pregnancy, NebiletЃ is prescribed only for vital indications, when the benefit to the mother outweighs the possible risk to the fetus or newborn (due to the possible development of bradycardia in the fetus and newborn, arterial hypotension, hypoglycemia).

If treatment with NebiletЃ 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 observation of the newborn within 48-72 hours after delivery.

Nebivolol is excreted in breast milk. If it is necessary to take NebiletЃ during lactation, breastfeeding should be discontinued.

Method of administration and dosage:

NebiletЃ tablets are taken orally, once a day, preferably at the same time, regardless of food intake, with a sufficient amount of liquid.

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

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

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

The selection of the dose at the beginning of treatment should be carried out according to the following scheme: while maintaining intervals from one to two weeks and focusing on the tolerance of this dose by the patient: a dose of 1.25 mg of NebiletЃ (1/4 of a 5 mg tablet) 1 time per day, can be increased first to 2.5 - 5 mg once a day of the drug NebiletЃ (1/2 tablet of 5 mg or 1 tablet), and then to 10 mg (2 tablets of 5 mg) once a day ...

The maximum daily dose is 10 mg once a day.

At the beginning of treatment and with each dose increase, the patient should be under medical supervision for at least 2 hours to make sure that the clinical condition remains stable (especially: blood pressure, heart rate, conduction disturbances, as well as symptoms of worsening chronic heart failure). To divide, place the tablet on a hard, flat surface with a cruciform notch up, press down on the tablet with both index fingers. For a quarter (1/4) tablet, repeat the same steps with half (1/2) tablet.

Side effect

From the side of the central nervous system and peripheral nervous system: often - headache, dizziness, fatigue, weakness, paresthesia; infrequently - depression, nightmares, confusion; very rarely - fainting, hallucinations.

From the digestive system: often - nausea, constipation, diarrhea; infrequently - dyspepsia, flatulence, vomiting.

From the side of the cardiovascular system: infrequently - bradycardia, acute heart failure, AV block, orthostatic hypotension, Raynaud's syndrome.

On the part of the skin and subcutaneous tissues: infrequently - an erythematous skin rash, itching; very rarely - worsening of the course of psoriasis; in some cases - angioedema.

Others: infrequently - bronchospasm; rarely - dry eyes.

Application for violations of liver function

Contraindicated in severe liver dysfunction.

Application for impaired renal function

In patients with renal insufficiency, the initial dose is 2.5 mg / day.

Application in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

The drug should be used with caution in patients over the age of 75 years.

special instructions

Cancellation of beta-blockers should be carried out gradually over 10 days (up to 2 weeks in patients with coronary artery disease).

Control of blood pressure and heart rate at the beginning of taking the drug should be daily.

In elderly patients, it is necessary to monitor kidney function (once every 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 - 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.

ѕри решении вопроса о применении препарата ЌебилетЃ у пациентов с псориазом следует тщательно соотнести предполагаемую пользу от применени¤ препарата и возможный риск обострени¤ течени¤ псориаза.

ѕациенты, пользующиес¤ контактными линзами, должны учитывать, что на фоне применени¤ бета-адреноблокаторов возможно снижение продукции слезной жидкости.

ѕри проведении хирургических вмешательств следует предупредить врача-анестезиолога о том, что пациент принимает бета-адреноблокаторы.

Ќебиволол не вли¤ет на концентрацию глюкозы в плазме крови у пациентов с сахарным диабетом. “ем не менее, следует соблюдать осторожность при лечении этих пациентов, поскольку препарат ЌебилетЃ может маскировать определенные симптомы гипогликемии (например, тахикардию), вызванные применением гипогликемических средств дл¤ приема внутрь и инсулина.  онтроль концентрации глюкозы в плазме крови следует проводить 1 раз в 4-5 мес (у больных с сахарным диабетом).

ѕри гиперфункции щитовидной железы бета-адреноблокаторы могут маскировать тахикардию.

Ѕета-адреноблокаторы следует примен¤ть с осторожностью у пациентов с хронической обструктивной болезнью легких, поскольку может усилитьс¤ бронхоспазм.

Ѕета-адреноблокаторы могут повысить чувствительность к аллергенам и т¤жесть анафилактических реакций.

¬ли¤ние на способность к управлению транспортными средствами и механизмами

¬ли¤ние препарата ЌебилетЃ на способность к вождению транспортных средств и управлению механизмами специально не изучалось. »сследовани¤ фармакодинамики небиволола показали, что препарат ЌебилетЃ не оказывает вли¤ни¤ на психомоторную функцию. ¬ период лечени¤ препаратом ЌебилетЃ (при возникновении побочных эффектов) следует соблюдать осторожность при вождении транспортных средств и при зан¤ти¤х потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

ѕередозировка

—имптомы: выраженное снижение ј?, тошнота, рвота, цианоз, синусова¤ брадикарди¤, AV-блокада, бронхоспазм, потер¤ сознани¤, кардиогенный шок, кома, остановка сердца.

Ћечение: промывание желудка, прием активированного угл¤. ¬ случае выраженного снижени¤ ј? необходимо придать пациенту горизонтальное положение с приподн¤тыми ногами, при необходимости в/в введение жидкости и вазопрессоров. ѕри брадикардии следует вводить в/в 0.5-2 мг атропина при отсутствии положительного эффекта возможна постановка трансвенозного или внутрисердечного электростимул¤тора. ѕри AV-блокаде (II-III ст.) рекомендуетс¤ в/в введение бета-адреностимул¤торов, при их неэффективности следует рассмотреть вопрос о постановке искусственного водител¤ ритма. ѕри сердечной недостаточности лечение начинают с введени¤ сердечных гликозидов и диуретиков, при отсутствии эффекта целесообразно введение допамина, добутамина или вазодилататоров. ѕри бронхоспазме примен¤ют в/в стимул¤торы ?2-адренорецепторов. ѕри желудочковой эстрасистолии - лидокаин (нельз¤ вводить антиаритмические средства Iј класса).

Ћекарственное взаимодействие

‘армакодинамическое взаимодействие

ѕри одновременном применении бета-адреноблокаторов с блокаторами медленных кальциевых каналов (верапамил и дилтиазем) усиливаетс¤ отрицательное действие на сократимость миокарда и AV-проводимость.

ѕротивопоказано в/в введение верапамила на фоне применени¤ небиволола.

ѕри одновременном применении небиволола с гипотензивными средствами, нитроглицерином или блокаторами медленных кальциевых каналов может развитьс¤ выраженна¤ артериальна¤ гипотензи¤ (особа¤ осторожность необходима при сочетании с празозином).

ѕри одновременном применении небиволола с антиаритмическими препаратами I класса и с амиодароном возможно усиление отрицательного инотропного действи¤ и удлинение времени проведени¤ возбуждени¤ по предсерди¤м.

ѕри одновременном применении небиволола с сердечными гликозидами не вы¤влено усилени¤ вли¤ни¤ на замедление AV-проводимости.

ќдновременное применение небиволола и препаратов дл¤ общей анестезии может вызывать подавление рефлекторной тахикардии и увеличивать риск развити¤ артериальной гипотензии.

 линически значимого взаимодействи¤ небиволола и Ќѕ¬ѕ не установлено.

ќдновременное применение небиволола с трициклическими антидепрессантами, барбитуратами и производными фенотиазина может усиливать гипотензивное действие небиволола.

‘армакокинетическое взаимодействие

ѕри одновременном применении небиволола с препаратами, ингибирующими обратный захват серотонина, или другими средствами, биотрансформирующимис¤ с участием изофермента CYP2D6, повышаетс¤ концентраци¤ небиволола в плазме крови, метаболизм небиволола замедл¤етс¤, что может привести к риску возникновени¤ брадикардии.

ѕри одновременном применении с дигоксином небиволол не оказывает вли¤ни¤ на фармакокинетические параметры дигоксина.

ѕри одновременном применении небиволола с циметидином концентраци¤ небиволола в плазме крови увеличиваетс¤.

ќдновременное применение небиволола и ранитидина не оказывает вли¤ни¤ на фармакокинетические параметры небиволола.

ѕри одновременном применении небиволола с никардипином концентрации активных веществ в плазме крови несколько увеличиваютс¤, однако это не имеет клинического значени¤.

The simultaneous administration of nebivolol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

There is no clinically significant interaction between nebivolol and warfarin.

When nebivolol is used together with insulin and oral hypoglycemic agents, symptoms of hypoglycemia (tachycardia) may be masked.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25 ? C.

Shelf life

Shelf life is 3 years.

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

BERLIN-CHEMIE / MENARINI PHARMA GMBH (Germany)

123317 Moscow, Presnenskaya emb. 10
Business Center 'Tower on the Embankment', Block B
Tel .: (495) 785-01-00; Fax: (495) 785-01-01