Nebikard

General characteristics. Structure:

Active ingredient: 2,5 mg or 5 mg of a nebivolol in the form of a nebivolol of a hydrochloride.

Excipients: lactoses monohydrate, starch corn, sodium of a kroskarmelloz, gidroksipropilmetiltsellyuloz, polysorbate 80, cellulose microcrystallic, magnesium stearate, silicon dioxide colloid anhydrous.

Pharmacological properties:

Pharmacodynamics. Nebivolol represents the racemate consisting of two enantomer: SRRR небиволола (D-nebivolol) and RSSS небиволола (L-nebivolol). It combines two pharmacological properties:

- thanks to D-enantomeru небиволол is a competitive and selection blocker β1 - adrenoceptors,

- thanks to L-enantomeru it has "soft" vazodilatatorny properties owing to metabolic interaction with L-argininom/oksidom of nitrogen (NO).

At single and repeated use of a nebivolol heart rate at rest decreases and at loading as at persons with normal arterial pressure, and at patients with arterial hypertension. The anti-hypertensive effect at prolonged treatment remains. In therapeutic doses α-adrenergic antagonism is not observed. Nebivolol has no sympathomimetic activity. In pharmacological doses of a membranostab_l_zuyuch activity of a nebivolol is absent. Nebivolol has no significant effect on tolerance to an exercise stress.

Pharmacokinetics. After oral administration there is a bystry absorption of both enantomer of a nebivolol. The food does not influence absorption of a nebivolol therefore it can be accepted irrespective of meal. Nebivolol is metabolized in a liver, in particular with formation of active hydroxymetabolites. Metabolism of a nebivolol is connected with genetic oxidizing polymorphism which depends on CYP2D6. Bioavailability of orally entered nebivolol averages 12% at fast-metabolizing persons and is almost full at persons with a slow metabolization. Proceeding from a metabolization speed difference, Nebikard's dosage it is necessary to establish depending on individual needs of the patient, persons with a slow metabolization demand lower doses. At persons with a bystry metabolization value of an elimination half-life of enantomer of a nebivolol from a blood plasma 10 hours, and at persons with slow a metabolization average these values in 3-5 times more. At persons with a bystry metabolization concentration RSSS небиволола in a blood plasma is slightly higher, than SRRR небиволола. The age of the person does not influence pharmacokinetics of a nebivolol. In 1 week after reception about 38% of a dose of drug are removed with urine, 48% – with a stake. In not changed state with urine no more than 0,5% of a nebivolol are removed.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Drug is used irrespective of meal, washing down with enough liquid. It is desirable to carry out administration of drug at the same time.

Arterial hypertension. The dose makes 1 tablet a day, it is better to accept at the same time. The pill can be taken during food. The anti-hypertensive effect is shown through

1-2 weeks of treatment. In certain cases optimal effect is reached only in 4 weeks.

Blockers of β-adrenoceptors can be applied as monotherapy or in a combination with other hypotensive drugs. The additional hypotensive effect is reached at the combined reception of 5 mg of Neb_kardu and 12,5-25 mg of Hydrochlorthiazidum.

Patients with a renal failure: an initial dose – 2,5 mg a day. If necessary it is possible to increase a daily dose to 5 mg.

Patients with a liver failure: experience of use of drug by such patient is limited therefore use of a nebivolol is contraindicated.

Patients of advanced age: to patients 65 years the recommended initial daily dose are aged more senior makes 2,5 mg a day. If necessary it is possible to increase a daily dose to 5 mg. Experience of use of drug to patients is aged more senior than 75 years is limited therefore at purpose of drug care and careful control are necessary for such patients.

Features of use:

Use during pregnancy or feeding by a breast. Do not apply.

Children. Do not apply.

Features of use. At observation of patients who accepted небиволол within 3 years development of tolerance to it it was not observed. Blockers of β-adrenoceptors can be applied both to monotherapy, and in a combination with other anti-hypertensive drugs. By this time the additional hypotensive effect was studied in clinical trial only at the combined use of a nebivolol and 12,5-25 mg of Hydrochlorthiazidum.

The general for blockers of β-adrenoceptors are certain preventions and precautionary measures.

Anesthesia. Maintenance of blockade of β-adrenoceptors reduces risk of disturbances of a cordial rhythm during introduction to an anesthesia and intubations. If by preparation for surgical intervention blockade

β-adrenoceptors rummage, not less than in 24 hours it is necessary to stop use of blockers of β-adrenoceptors before.......... Care is necessary at use of the separate anesthetics causing oppression of a myocardium such as cyclopropane, ether or trichloroethylene. Emergence of vagal reactions in the patient can be prevented by means of intravenous administration of atropine.

Heart and vessels. As a rule, patients with dekompensirovanny chronic heart failure should not appoint blockers of β-adrenoceptors until their state does not become stable. It is necessary to stop therapy by a blocker of β-adrenoceptors to patients with coronary heart disease gradually, that is within 1-2 weeks. If necessary, to prevent an exacerbation of a disease, it is recommended to begin treatment with drug-substitute at the same time.

Blockers of β-adrenoceptors can cause bradycardia. If pulse at rest decreases to 50-55 beats per minute and/or at the patient the symptoms indicating bradycardia develop, recommend to reduce a dose.

Blockers of β-adrenoceptors should be applied with care at treatment:

- patients with disturbances of peripheric circulation (Reynaud's syndrome, the alternating lameness) as the exacerbation of the specified diseases can develop,
- patients with an atrioventricular block have degree i in connection with a negative impact of blockers of β-adrenoceptors on conductivity,
- patients with Printsmetal's stenocardia owing to possible, mediated
a-adrenoceptors, vasoconstrictions of coronary arteries (blockers of β-adrenoceptors can increase the frequency and duration of attacks of stenocardia).

The combination of a nebivolol with antagonists of calcium like verapamil and diltiazem, And a class of antiarrhytmic means, anti-hypertensive central acting agents is not recommended (see the section "Interaction with Other Medicines and Other Types of Interactions").

Metabolism and endocrine pathology. Nebivolol does not influence the content of glucose at patients with a diabetes mellitus. Despite it, it is necessary to be careful at its use for treatment of patients of this category as небиволол can mask some signs of a hypoglycemia, for example tachycardia and the strengthened heartbeat. Blockers of β-adrenoceptors can mask tachycardia symptoms, at hyperfunction of a thyroid gland. At the sudden termination of therapy these symptoms can amplify.

Respiratory tracts. Patients with obstructive respiratory diseases should apply blockers of β-adrenoceptors with care as the konstriktion of respiratory tracts can amplify.

Another. Before appointing blockers of β-adrenoceptors sick with psoriasis in the anamnesis, it is necessary to weigh carefully a ratio between possible risk and advantage of their use.

Blockers of β-adrenoceptors can increase sensitivity to allergens and severity of anaphylactic reactions.

It is necessary to watch patients with chronic heart failure, it is necessary to cancel drug gradually.

It is necessary to use with care drug at a pheochromocytoma, a myasthenia, a depression.

Because of insufficient experience of treatment by drug to patients 75 years are more senior it is necessary to use drug under careful observation of the doctor.

Drug contains lactose therefore it should not be applied at hereditary intolerance of a galactose, deficit of lactase of Lapp or disturbance of malabsorption of glucose galactose.

Ability to influence speed of response at control of motor transport or work with other mechanisms. At control of motor transport or work with other mechanisms it is necessary to consider that in an initiation of treatment drug the lowering of arterial pressure, dizziness and feeling of fatigue can sometimes take place. Before clarification of individual reaction of the patient to drug it is necessary to refrain from control of motor transport or work with other mechanisms.

Side effects:

From immune system: Quincke's disease, hypersensitivity reactions.

Mental disorders: awful night dreams, depression.

From a nervous system: headache, dizziness, paresthesia, syncope.

From an organ of sight: vision disorder.

From cardiovascular system: bradycardia, heart failure, lengthening of atrioventricular conductivity, an atrioventricular block, arterial hypotension, strengthening of the alternating lameness.

From respiratory system: asthma, bronchospasm.

From a digestive tract: lock, nausea, diarrhea, dyspepsia, meteorism, vomiting, abdominal pain, hepatotoxic action.

From skin: allergic reactions, skin itch, skin reactions of erythematous character, exacerbation of psoriasis.

From reproductive system: erectile disturbances, impotence.

General frustration: feeling of fatigue, hypostases.

From a musculoskeletal system: muscular weakness, spasms, muscle pain.

The following side reactions were reported for beta adrenoblockers: hallucinations, psychoses, confusion of consciousness cold / цианотичны extremities, Reynaud's syndrome, xerophthalmus, toxic damage of a mucous membrane of eyes.

Interaction with other medicines:

Drug cannot be used with such drugs as:

- флоктафенин: β-blockers can interfere with the compensatory reactions of cardiovascular system associated with arterial hypotension or shock which can be caused floktafeniny.
- сультоприд: at combined use of drugs the increased risk of developing of ventricular arrhythmia is observed.

Pharmakodinamichesky interactions. Interaction is not recommended. Antiarrhytmic means And class: quinidine, hydroquinidine, цибензолин, флекаинид, Disopyramidum, lidocaine, мекселитин, пропафенон – is exponentiated influence on atrioventricular conductivity, negative inotropic effect increases.

Antagonists of calcium like verapamil / дилтиазем – a negative impact on contractility and atrioventricular conductivity At a combination of blockers of β-adrenoceptors like verapamil and diltiazem it is necessary to be careful with antagonists of calcium in connection with their negative inotropic effect and influence on atrioventricular conductivity. Intravenous administration of verapamil is contraindicated to patients who accept Nebikard as can bring to the expressed arterial hypotension and an atrioventricular block.

Anti-hypertensive preprat of the central action (clonidine, гуанфацин, моксонидин, Methyldopum, рілменидин): an aggravation of symptoms at heart failure owing to decrease in a tone of a sympathetic nervous system (reduction of heart rate and cordial emission). Sudden cancellation can increase risk of emergence of a syndrome of "ricochet". At the sudden termination of prolonged treatment by a clonidine blockers of β-adrenoceptors increase risk of development of "withdrawal" with increase in arterial pressure therefore cancellation should be carried out gradually.

Combinations which should be applied with care. Antiarrhytmic means of the III class (Amiodaronum): influence on atrioventricular conductivity can be exponentiated.

Anesthetics. Simultaneous use of β-adrenoblockers and anesthetics can oppress reflex tachycardia and increase risk of development of arterial hypotension. The anesthesiologist needs to be informed on what the patient accepts Nebikard.

Insulin and peroral antidiabetic means. Though Nebikard does not influence glucose level, it can mask some symptoms of a hypoglycemia, for example, tachycardia, heartbeat.

Simultaneous use with Baclofenum and amifostiny promotes an exacerbation of arterial hypotension, the dose of hypotensive drugs should be reduced.

Theoretically simultaneous use of Nebikard with meflokviny can lead to lengthening of an interval of QT.

Combinations about which it is necessary to report. Cardiac glycosides. Foxglove glycosides in combination with blockers of β-adrenoceptors can extend time of atrioventricular carrying out. Clinical trials did not show any interaction, небиволол does not influence digoxin kinetics.

Antagonists of calcium of dihydropyridinic type (амлодипин, фелодипин, лацидипин, nifedipine, никардипин, нимодипин, нитрендипин): their simultaneous use can increase risk of developing of arterial hypotension and it is impossible to exclude risk of deterioration in ventricular contractility.

Antipsychotic means, antidepressants (tricyclic antidepressants, barbiturates and фенотиазин): their simultaneous use can increase hypotensive action of beta-blockers (the additive action).

Non-steroidal anti-inflammatory drugs (NPVP): simultaneous use of a nebivolol with нпвп does not influence its anti-hypertensive action.

Sympathomimetic means. Sympathomimetic means can counteract activity

β-adrenoblockers.......... Blockers of β-adrenoceptors can result in free α-adrenergic activity of simpatikoton_chny means as with α-adrenergic, and with β-adrenergic action (danger of development of arterial hypertension, heavy bradycardia, an atrioventricular block).

Pharmacokinetic interactions. As in the course of metabolism of a nebivolol CYP2D6 isoenzyme, the accompanying drug treatment by drugs which inhibit the return serotonin reuptake, for example, пароксетин, fluoxetine, thioridazine, quinidine, dextromethorphan or other connections which are metabolized preferential in the same metabolic way takes part, can promote that reaction of persons with bystry metabolism will become similar to reaction of persons with a slow metabolization, the risk of bradycardia and other side reactions increases.

At simultaneous use of Cimetidinum the level of a nebivolol in a blood plasma, but without change of clinical activity increased. Simultaneous use of ranitidine of influence on pharmacokinetics of a nebivolol did not render. Provided that Nebikard is accepted during food, and antiacid means – between meals, both drugs can be accepted together. At a combination with nikardipiny values of concentration of both substances in a blood plasma without change of clinical activity increased. The concomitant use of furosemide and Hydrochlorthiazidum, and also use of ethanol of influence on pharmacokinetics does not render. Nebivolol did not exert impact on a pharmacodynamics and pharmacokinetics of warfarin.

Contraindications:

Hypersensitivity to active ingredient or to any of excipients. A liver failure or an abnormal liver function, an acute heart failure, cardiogenic shock, dekompensirovanny heart failure which demands use of _notropny means, a sick sinus syndrome, a sinoauricular block, an atrioventricular block of II and III degrees (without artificial pacemaker), a bronchospasm and bronchial asthma in the anamnesis, not treated pheochromocytoma, a metabolic acidosis, bradycardia (heart rate is less than 60 blows in a minute), arterial hypotension (systolic pressure is lower than 90 mm hg), heavy disturbances of peripheric circulation. Simultaneous use with floktafeniny and sultopridy. Pregnancy and period of feeding by a breast.

Overdose:

Symptoms: bradycardia, arterial hypotension, bronchospasm and acute heart failure.

In case of overdose or development of giperergichesky reaction it is necessary to provide constant medical observation of the patient and rendering intensive medical care to it.

It is recommended to control the level of content of glucose in blood. Absorption of active ingredient which still contains in a digestive tract can be prevented by a gastric lavage, administration of absorbent carbon and purgatives. Carrying out artificial ventilation of the lungs can be required.

For elimination of bradycardia administration of atropine or methylatropine is recommended. Treatment of arterial hypotension and shock should be carried out by means of plasma or plasma substitutes and if there is in it a requirement, catecholamines. the β-blocking action can be stopped slow intravenous administration of an izoprenalin of a hydrochloride, since a dose of 2,5 mkg/min., till that time, the expected effect will not be established yet. In case of immunity it is possible изопреналин to combine with a dopamine. If this measure does not result in desirable result, it is possible to apply intravenous administration of 50-100 mkg/kg of a glucagon.

If necessary the injection within 1 hour should be repeated and further if it is necessary, to carry out intravenous drop infusion of a glucagon at the rate of 70 mkg/kg/h. In extreme cases, for example, at bradycardia, resistant to therapy, it is possible to use a pacemaker.

Storage conditions:

Period of validity - 3 years. To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, on 2 or 5 blisters combined in one in cardboard packaging.