Nebivator - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 143.475 mg, corn starch 34.5 mg, croscarmellose sodium 13.8 mg, hypromellose 3.45 mg, cellulose microcrystalline 26.45 mg, silicon colloidal dioxide 0.575 mg, magnesium stearate 2.3 mg.

Description:

White or almost white round biconvex tablet with a cross-shaped risk on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is an lipophilic, cardioselective beta₁-adrenergic blocker of the third generation with vasodilating properties. Provides hypotensive, antianginal and antiarrhythmic action. Nebivolol reduces heart rate (heart rate) and lowers blood pressure (BP) at rest and under physical exertion, reduces the final diastolic pressure of the left ventricle, improves the diastolic function of the heart, reduces the overall peripheral vascular resistance, increases the ejection fraction. Competitively and selectively blocks synaptic and postsynaptic beta₁-adrenoceptors, making them inaccessible for catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide (N0).

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

- D-nibilol is a competitive and highly selective blocker beta₁- adrenergic receptors (affinity for beta₁-adrenoceptors 293 times higher than to beta₂adrenoreceptors);

- L- Nebivolol has a vasodilator action due to modulation of release relaxing factor (NO) from the endothelium vessels.

The hypotensive effect is also due to decreased activity of renin-angiotensin-aldosterone system (not directly correlates with changes in renin activity in the blood plasma). Hypotensive effect comes on the 2nd - 5th day of treatment, stable the action is celebrated in 1-2 months. This effect persists for a long time treatment. Reducing the need for myocardium in oxygen (decreasing heart rate, reducing preload and post loading), nebivolol reduces the number and severity of angina attacks and improves tolerability of physical activity.

Antiarrhythmic action due to suppression of heart's automaticity (including in pathological focus) and slowing of atrio- ventricular (AV) conductivity.

Pharmacokinetics:

Suction

After ingestion, both enantiomers Nebivolol is rapidly 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 (the "first pass" effect) and is almost complete in patients with "slow" metabolism.

Distribution

Connection with blood plasma proteins (mainly with albumin) for DThe nebivolol is 98.1%, and for L- nebivolol - 97.9%.

Metabolism

Metabolized with the formation of active metabolites by alicyclic and aromatic hydroxylation andof the N-dealkylation; formed guideThe roxy- and amino-derivatives are conjugated with glucuronic acid and are derived as O-and N - Glucurones. Metabolic rate nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on CYP2D6.

Excretion

A week after the introduction of 38% (the amount of unchanged active of the substance is less than 0.5%), the dose is excreted by the kidneys and 48% by the intestine.

In patients with a "fast" metabolism half-life (T_1/2) enantiomers Nebivolol from plasma is in average 10 hours. In patients with a "slow" metabolism, this value increases in 3-5 times.

In patients with a "fast" metabolism T_1/2hydroxymetabolites of both enantiomers from blood plasma is an average of 24 hours, patients with a "slow" metabolism is value increases approximately in 2 times.

The age of the patient does not affect the pharmacokinetics of nebivolol.

Indications:

- Arterial hypertension;

- ischemic heart disease: prevention attacks of stable angina pectoris;

- chronic heart failure (as part of combination therapy)

Contraindications:

Hypersensitivity to nebivolol or any of the components of the preparation; severe hepatic impairment; acute heart failure; cardiogenic shock; chronic heart failure in the stage of decompensation (requiring intravenous administration of drugs, possessing an inotropic effect); syndrome weakness of the sinus node, including sinoatrial blockade; atriovent-ricular (AV) blockade of II and III degree (in absence of an artificial pacemaker); bronchial asthma or bronchospasm in anamnesis; pheochromocytoma (without one-shotapplication of alpha-adrenoblockers); depression; metabolicacidic acidosis; pronounced bradycardia (heart rate less than 60 bpm); pronounced arterial hypotension (systolic arterial pressure less than 90 mm Hg); myasthenia gravis, muscle weakness; age to 18 years; nepelactose deficiency, lactase deficiency, or Glucose-galactose malabsorption (drug contains lactose); pronounced violations peripheral circulation (""lame", Raynaud's syndrome), oneFlocking with floktaphenin, sulto(see section "Interaction with other drugs ").

Carefully:

Renal failure, hyperthyroidism, allergic diseases in the anamnesis, psoriasis, AV blockade of I degree, diabetes mellitus, chronic obstructive pulmonary disease, desensitizing therapy, prinzmetal angina, elderly patients (over 65 years).

Pregnancy and lactation:

At pregnancy appoint or nominate only under strict indications, when advantage for mother preexposes the risk to the fetus (in connection with the possibledevelopmental delay and fetal growth, intrauterine fetal death, premature birth, as well as development of newborn bradycardia, decrease blood pressure, hypoglycemia and paralysis of respiration). Treatment is necessary interrupt for 48 -72 hours before delivery. In those cases where this is not possible, it is necessary to to control utero-placental blood flow and fetal growth, and provide strict observation of newborns during the first three days after delivery. Studies in animals have shown that nebivolol is excreted with the milk of lactating animals.

If the drug is used during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Nebivator ® is taken orally at the same time of the day, regardless of food intake, without chewing and washing down with sufficient number of liquid.

The tablet can be divided into four equal parts according to the cruciform risk.

Arterial hypertension (AP and ischemic heart disease (CHD):

The average daily dose is 2.5 - 5 mg of Nebivator ® (1 / 2-1 tablets of 5 mg) once a day. Clinically significant effect appears after 1-2 weeks of treatment, and in some cases - after 4 weeks. It is possible to use the drug in monotherapy or as part of a combination therapy.

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

In patients with renal insufficiency (creatinine clearance more than 20 ml / min), as well as 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 5 mg (1 tablet of 5 mg).

Chronic heart failure (CHF):

Treatment of chronic heart failureshould begin with a gradual increase in the dose until an individual optimal maintenance dose is reached. Patients should not have attacks of acute heart failure within the last 6 weeks. It is recommended to carry out treatment under close supervision of a doctor.

For patients receiving medication for cardiovascular disease, including diuretics, digoxin, angiotensin-converting enzyme inhibitors and / or angiotensin II receptor antagonists, the dose of these drugs should be stabilized in the last 2 weeks before treatment with Nebivator®.

Dose selection at the beginning of treatment should be carried out in stages, maintaining 2 weeks intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg of Nebivator® (1/4 tablets 5 mg) once a day can be increased first to 2.5-5 mg of Nebivator (1 / 2-1 tablets of 5 mg) once a day, and then - up to 10 mg (2 tablets of 5 mg) once a day. The patient should be under the supervision of a doctor within 2 hours after taking the first dose of the drug, and also after each subsequent increase in the dose.

The maximum recommended dose for the treatment of CHF is 10 mg of Nebivator ® once a day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended. During titration, in case of worsening of the course of chronic heart failure or intolerance of the drug, it is recommended to reduce the dose of Nebivatore ® or, if necessary, to stop it immediately (in case of pronounced arterial hypotension, worsening of the course of CHF with acute pulmonary edema,in case of development of cardiogenic shock, symptomatic bradycardia or AV blockade).

The treatment of stable CHF with the Nebivator® preparation is usually prolonged. Treatment with Nebivator is not recommended to stop suddenly (if it is not necessary), because this can lead to transient deterioration of heart failure. If necessary, the dose should be reduced gradually (half every week).

In patients with mild or moderate renal failure, as well as in patients older than 65 years the choice of dose is not required, since titration up to the maximum tolerated dose is carried out on an individual basis.

Side effects:

According to the World Organization health (WHO) the effects are classified according to the frequency of their development as follows:

Often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1 / 10000, including individual messages), the frequency is unknown (it is impossible to estimate the frequency of development from available data).

From the immune system: frequency unknown - angioedema, hypersensitivity;

From the side of the psyche: infrequently - "nightmarish" dreaming, depression; very rarely - a gullycognition, psychosis, confusion;

From the nervous system: often - headache, dizziness, paresthesia, weakness; very rarely - a syncope;

From the side of the organs of sight: violation of vision, dry eyes;

From the side of the cardiovascular system: very often bradycardia¹, often aggravation of chronic heart failure¹, atrioventricular block of degree I¹, orthostatic hypotension¹; infrequent - bradycardia, heart failure, slowing of atrioventricular conduction / atrioventricular blockade, lowering of arterial pressure, progression of concomitant "intermittent" lameness; very rarely - Raynaud's syndrome.

On the part of the respiratory system, the organs of the thorax and the mediastinum: often - shortness of breath; infrequently - bronchospasm.

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

From the skin and subcutaneous tissues: often swelling¹; infrequently - itchy skin, erythematous rash; very rarely exacerbation of psoriasis, toxic effects of preparations of the group of pratolol on the eyes, skin and mucous membranes.

From the side of the reproductive system: infrequently erectile dysfunction.

General disorders and disorders at the site of administration: very often - dizziness¹; often - increased fatigue, swelling, drug intolerance¹; very rarely - cold / cyanosis of the extremities.

¹ - in patients with CHF.

Overdose:

Symptoms: marked decrease in blood pressure, expressionbradycardia, AV blockade, cardiogenshock, acute heart failure, heart failure, bronchospasm, loss consciousness, coma, nausea, vomiting, cyanosis, hypoglycemia.

Treatment: the patient is hospitalized and placed in the intensive care unit.

Gastric lavage is activated carbon. In the case of a pronounced reduce blood pressure should be given to the patient horizontal position with raised feet, if necessary iv administration liquid and vasopressors; as follow-up glucagon (50-100 μg / kg). When expressed bradycardia is administered intravenously (iv) 0.5-2 mg atropine, in the absence of a positive effect is possible setting transvenous or an intracardiac electrostimulator.

When AV blockade (II-III century) is recommended in / in introduction of beta-adrenomimetics, with their Inefficiency should consider installing 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, dobutimi- on or vasodilators. When bronhospazme enter intravenously betag-adrenomimetiki. With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class). When hypoglycemia - the administration of a solution of dextrose (glucose).

Interaction:

Pharmacodynamic interaction With simultaneous use with antiarrhythmic drugs I class (quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexylitol, propafenone) it is possible to increase the negative inotropic effect and prolong the time of excitation in the atria.

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

Contraindicated in / in the introduction of verapamil against nebivolol.When combined with antihypertensive drugs, nitroglycerin or BCCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin). With simultaneous use with antihypertensive drugs from the centermechanism of action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen heart failure by reducing the sympathetic tone (decreased heart rate and cardiac output, vasodilation). In the case of a sudden withdrawal of these drugs, especially before the abolition of nebivolol, the development of the "withdrawal" syndrome is possible.

With simultaneous use with antiarrhythmic drugs of III class (amiodarone) it is possible to prolong the excitation time at the atria. Simultaneous use of beta-blockers and drugs for general anesthesia can cause suppression of reflex tachycardia and increase the risk of developing arterial hypotension. The concomitant use of insulin and hypoglycemic oral medications can mask some of the symptoms of hypoglycemia (heart palpitations, tachycardia).Simultaneous use of nebivolol with cardiac glycosides may cause a slowdown AV conductivity. However, no clinical studies of nebivolol indicated this interaction. Nebivolol does not affect the pharmacokinetics of digoxin.

Concomitant use of nebivolol and BCCC dihydropyridine series (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of developing arterial hypotension. It can not be ruled out that the risk of further impairment of the pumping function of the ventricles increases in patients with heart failure.

The simultaneous use of tricyclic antidepressants, barbiturates and phenothiazine derivatives can enhance the antihypertensive effect of beta-blockers. 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. With the simultaneous use of sympathomimetic agents can inhibit the activity of beta-blockers.Active substances with beta-adrenergic effect can lead to unhindered alpha-adrenergic activity of sympathomimetics with the presence of both alpha and beta-adrenergic effects (the risk of developing hypertension, severe bradycardia and cardiac blockade).

Contraindicated simultaneous use of nebivolol and floktaphenina. Exist the threat of a marked decrease in blood pressure or shock. Contraindicated simultaneous use of nebivolol and sultopride. The risk of ventricular arrhythmia increases.

The simultaneous use of baclofen and amifostine with antihypertensive drugs can cause a significant drop in blood pressure, therefore, a correction of the dose of antihypertensive drugs is required.

Theoretically, co-administration of mefloquine with nebivolol may lead to lengthening of the interval QT.

Pharmacokinetic interaction

Application in combination with drugs that inhibit serotonin reuptake, or other means, biotransforming with the participation of isoenzyme CYP2D6 (eg, paroxetine, fluoxetine, thioridazine, quinidine) can lead to an increase in the concentration of nebivolol in the blood plasma, thereby increasing the risk of developing excessive bradycardia and other side effects.With simultaneous use with cimetidine, the concentration of nebivolol in the blood plasma increases without changing the clinical effect. The simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardipine, the concentrations of both substances in the blood plasma increase slightly without changing the clinical effect. The simultaneous use of ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetic parameters of nebivolol.

Special instructions:

Patients with untreated CHF beta-blockers should not be appointed until their condition becomes stable. At the beginning of CHF treatment, the patient's condition must be carefully monitored. It is unacceptable to suddenly stop taking beta-blockers; the abolition of beta-blockers should be carried out gradually, within 10 days (in patients with IHD, 1-2 weeks).

Beta-blockers can cause bradycardia: the dose should be reduced if the heart rate at rest decreases to 50-55 beats / min and / or the patient develops symptoms indicating a bradycardia.The drug has no effect on the concentration of glucose in blood plasma in patients with diabetes mellitus. Nevertheless, caution should be exercised in the treatment of these patients, since Nebivator® may mask certain symptoms of hypoglycemia (tachycardia, heart palpitations), caused by the use of hypoglycemic means.

With hyperthyroidism the drug masks tachycardia.

When deciding whether to prescribe the drug Nebivator patients with psoriasis should carefully correlate the intended use from the use of the drug and the possible risk exacerbation of psoriasis.

Beta-adrenalosors can increase Sensitivity to allergens and degree the severity of anaphylactic reactions.

Patients wearing contact lenses, should take into account that against the background of beta-blockers may reduce production of tear fluid.

When conducting surgical interventions An anesthesiologist should be that the patient takes beta-adrenoblockers.

Pediatric Use

Clinical evidence of efficacy and safety of the drug in children up to 18 years are absent, therefore not It is recommended to prescribe the drug category of patients.

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

The effect of Nebivator® on ability to manage transport means and other mechanisms was studied.

When taking Nebivator ® follows take care when managing vehicles and occupations other potentially dangerous species activities that require increased attention and speed of psychomotor reactions (risk of dizziness and other side effects).

Form release / dosage:

Tablets of 5 mg.

Packaging:10 tablets in a blister of PVC film and aluminum foil. 3 or 10 blisters in a cardboard box together with instructions for use. 7 tablets in a blister of PVC film and aluminum foil. 2 or 4 blisters in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C in a dark place.

Keep out of the reach of children.

Shelf life:

4 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005947/09

Date of registration:21.07.2009 / 28.02.2014

Expiration Date:Unlimited

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp17.06.2018

Illustrated instructions

Instructions

Nebivator (Nebivator)