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

Excipients: lactose 148.00 mg, microcrystalline cellulose 20.00 mg, povidone-K25 5.00 mg, croscarmellose sodium 8.00 mg, silicon colloidal dioxide 1.65 mg, magnesium stearate 1.90 mg.

Description:

Round flat-cylindrical tablets of white or almost white color with a cross-shaped risk on one side and with a bevel.

Pharmacotherapeutic group:B-block selective blocker

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Cardioselective beta1-adrenoceptor with vasodilating properties. Nebivolol has antihypertensive, antianginal and antiarrhythmic action. It decreases the heart rate (HR) and lowers high blood pressure (BP) at rest, with physical activity, reduces the end-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 to catecholamines, modulates the release of the endothelial vasodilating factor of nitric oxide. Nebivolol is a racemate, consisting of two enantiomers: DNebivolol (SRRRnebivolol) and LNebivolol (RSSSNebivolol), combining two pharmacological actions:

- D-nibilol is a competitive and high-caliberblockade beta1-adrenoreceptors (affinity for beta1-adrenergic receptors is 293 times higher than for beta2-adrenoreceptors);

- L- Nebivolol has a vasodilating effect due to the modulation of the release of vasodilatizing factor from the vascular endothelium.

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

A stable antihypertensive effect develops after 1-2 weeks of regular intake of the drug, and in some cases - after 4 weeks, a stable effect is observed after 1-2 months. This effect persists with prolonged therapy.

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

Antiarrhythmic effect is due to suppression of pathological automatism of the heart (including in the pathological focus) and retardation of atrioventricular conduction.

Pharmacokinetics:

Suction

After oral administration, both enantiomers of nebivolol are rapidly absorbed from the gastrointestinal tract. Eating does not affect absorption, so nebivolol can be taken regardless of the time of ingestion. Biodeostability is an average of 12% in patients with "fast" metabolism (the effect of "primary transmission") and is almost complete in the Nazis with a "slow" metabolism.

Distribution

Clearance in the blood plasma in most patients (with a "fast" metabolism) is achieved within 24 hours, and for hydroxy metabolites - in a few days. Concentrations in blood plasma of 1-30 mcg / l are proportional to the dose.

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

Metabolism

Metabolized by the formation of active metabolites by al and cyclic and aromatic hydroxylation and partial N-dealkylation; the hydroxy and amino derivatives are conjugated to glucuronic acid and are recovered as O- and N- glucuron.

The metabolic rate of nebivolol by aromatic-hydroxylirvanation is genetically determined by oxidative polymorphism and is dependent on isoenzyme CYP2D6. The metabolic rate does not affect the effectiveness of nebivolol.

Excretion

One week after taking 38% (the amount of unchanged active substance is less than 0.5%), the dose is excreted by the kidneys and 48% by the intestine. In patients with "fast" metabolism, the values of the half-life (T1/2) enantiomers of nebivolol from the blood plasma averagely 10 hours. In patients with a "slow" metabolism, these values increase 3-5 times.

In patients with a "fast" metabolism T1 / 2 hydroxymetabolites of both enantiomers from blood plasma averagely 24 hours, in patients with a "slow" metabolism these values are approximately 2-fold increased. The age of the patient does not affect the pharmacokinetics of nebivolol.

Indications:

- arterial hypertension;

- ischemic heart disease: prevention of angina pectoris attacks;

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

Contraindications:

- hypersensitivity to nebivolol or other components of the drug and other beta-blockers;

- severe violations of liver function;

- acute heart failure;

- chronic heart failure in the stage of decompensation (requiring inotropic therapy);

- cardiogenic shock;

- syndrome of weakness of the sinus node, including sinoatrial block;

- atrioventricular blockade of II and III degree (without artificial pacemaker);

- bronchospasm and bronchial asthma in history;

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

- metabolic acidosis;

- bradycardia (heart rate less than 60 beats per minute);

- severe arterial hypotension (systolic blood pressure less than 90mmHg);

- depression;

- severe violations of peripheral circulation ("intermittent" lameness, Raynaud's syndrome);

- myasthenia gravis

- simultaneous administration with floktaphenin, sultopride (see section "Interaction with other medicinal products");

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

Impaired renal function (creatinine clearance (CC) less than 20 ml / min), liver disorders, diabetes mellitus, hyperthyroidism holding desensitizing therapy, allergic history, psoriasis, peripheral circulatory disorders, atrioventricular block I degree, Prinzmetal angina, chronic obstructive pulmonary disease, the use in elderly patients (older 65 years old).

Pregnancy and lactation:

Nebivolol can have harmful effects on the course of pregnancy, on the fetus and the newborn. The decrease in placental perfusion by the action of beta-blockers can cause fetal growth retardation, fetal death, miscarriage and premature birth. In newborns, there may be a bradycardia, a decrease in blood pressure, hypoglycemia and respiratory paralysis. Use during pregnancy is possible only if the expected benefit for the mother exceeds the potential risk to the fetus. Admission of the drug Bivotenz should be discontinued 48-72 hours prior to delivery. In cases where the ego is impossible, it is necessary to ensure strict observation of newborns within 48-72 hours after childbirth.

Studies in animals have shown that nebivolol is excreted with the milk of lactating animals. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, at the same time, regardless of the time of ingestion, ns chewing and drinking with a sufficient amount of liquid.
The tablet can be divided into four equal parts along a cruciform cut.

Arterial hypertension and ischemic heart disease

The average daily dose is 2.5-5 mg (1/2 tablet - 1 tablet of 5 mg) 1 time / day. The optimal effect becomes pronounced after 1-2 weeks of treatment, in some cases - after 4 weeks.

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

It is possible to use the drug in mop therapy or in combination with other hypotensive drugsby other means.

Chronic heart failure (CHF)

Treatment of stable CHF is necessary to begin with a gradual increase in the dose until an individual optimal maintenance dose is achieved. 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.

Patients who take diuretics, cardiac glycosides, aigiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, dosing of drugs should be stabilized 2 weeks prior to initiation of therapy with Biototenz.

Initiation of treatment with CHF by beta-adrenoreceptor blockers is necessary in the clinically stable state of the patient over the past 2 weeks. Selection of the dose at the beginning of therapy should be carried out according to the following scheme, maintaining 2-week intervals: a dose of 1.25 mg / day (1/4 tablets of 5 mg) can be increased to 2.5 mg / day (1/2 tablets but 5 mg), then - up to 5-10 mg / day (1-2 tablets of 5 mg). The patient should be under the supervision of the doctor within 2 hours after taking the first dose of the drug, and also after each subsequent increase in the dose. The maximum daily dose is 10 mg.

Each dose increase should be carried out not later than 2 weeks, depending on the individual tolerability of the drug.

During titration, regular monitoring of blood pressure, heart rate and symptoms of chronic heart failure is recommended.

During titration, in case of worsening of the course of CHF or intolerance to the drug, it is recommended to reduce the dose of the Biotenz preparation or, if necessary, to stop it immediately (in case of pronounced arterial hypotension, worsening of the course of CAS with acute pulmonary edema, in case of cardiogenic shock, symptomatic bradycardia or atrioventricular blockade).

Treatment of stable CHF is usually prolonged. Treatment with Biotenz is not recommended to be discontinued abruptly (if this is not the caseI need it), because thiscan lead to a temporary exacerbation of the course of CHF. If it is necessary to stop taking the drug, the cancellation is carried out gradually, reducing the dose within a week, twice. Patients with renal insufficiency (CC less than 20 ml / min): 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.

In patients with impaired renal function (creatinine clearance less than 20 ml / min.), an increase in the dose should be carried out with extreme caution.

Older patients: for patients older than 65 years, 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. However, taking into account the limited experience of the drug in elderly patients, it is necessary to be cautious and conduct a thorough examination of patients over the age of 65 years. In elderly patients, there is no need to adjust the dose, so it is necessary to individually select the dose, gradually increasing it to the maximum tolerated dose.

Side effects:

The incidence of side effects listed below was determined according to the following (classification of the World Health Organization): very often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), very rarely (less than 0.01%), the frequency is unknown (but it is impossible to estimate the frequency of development).

From the immune system:

frequency unknown: angioedema, gyneconclycle.

From the side of the psyche:

infrequently: "nightmarish" dreams, depression; very rarely: hallucinations, psychosis, with confusion.

Impaired nervous system:

often: headache, dizziness, weakness, paresthesia; very rarely - faint.

From the side of the organ of vision:

frequency unknown: impaired vision, dry eyes.

Disorders from the gastrointestinal tract:

often: nausea, constipation, diarrhea; infrequently: indigestion, flatulence, vomiting.

Disorders from the cardiovascular system:

very often: bradycardia, often: aggravation of CHF, atrioventricular block of degree 1¹, orthostatic hypotension¹; infrequent: bradycardia, heart failure, slowing of atrioventricular conduction / atrioventricular block, marked decrease in blood pressure, progression of concomitant "intermittent" lameness; very rarely: Raynaud's syndrome.

Disturbances from the skin and subcutaneous tissues:

often: edema¹; infrequent: skin rash of erythematous nature, itchy skin; very rarely: aggravation of psoriasis; frequency unknown: alopecia.

Disturbances from the respiratory system:

often: dyspnea;

infrequently: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis).

On the part of the reproductive system:

infrequently: erectile dysfunction.

Are common:

very often: dizziness¹; often: increased fatigue, swelling, drug intolerance¹; very rarely: cold / cyanosis of the extremities¹; infrequently: photodermatosis, hyperhidrosis;

1 - in patients with CHF.

Overdose:

Symptoms: marked decrease in blood pressure, severe bradycardia, acute heart failure, atrioventricular blockade, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, convulsions, coma, nausea, vomiting, hypoglycemia, cyanosis. Treatment: gastric lavage, reception of activated carbon. In the case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, intravenous fluid and vasopressors. When bradycardia should be administered intravenously, 0.5-2 mg of atropine, in the absence of a positive effect, a transvenous or intracardiac electrostimulator can be staged. In case of atrioventricular blockade (MI), intravenous administration of beta-adrenomimetics is recommended, in case of their ineffectiveness, the question of setting up an artificial pacemaker should be considered. With heart failure treatment begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to administer dopamine, dobutamine or vasodilatagors.

When bronhospazme apply intravenously beta₂- adrenomimetics.

With ventricular ekstrasistolii - lidocaine (do not administer antiarrhythmic drugs IA class).

With convulsions - intravenous diazepam.

In hypoglycemia, intravenous dextrose (glucose) can be indicated.

Interaction:

Pharmacodynamic interaction

With the simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCCC) (veranamyl and diltiazem) increases the negative effect on myocardial contractility and atrioventricular conductivity. Contraindicated intravenous administration of verapamil against nebivolol.

With the simultaneous use of nebivolol with antihypertensive drugs, nitroglycerin or BCCC, severe arterial hypotension may develop (special caution is necessary when combined with prazosin).

With simultaneous use with antihypertensive agents of central action (clonidine, guaifacin, moxoidin, methyldopa, rilmenidine) may worsen the course of heart failure by reducing the sympathetic tone (decreased heart rate and cardiac output, symptoms of vasodilation).In the case of abrupt withdrawal of these drugs, especially before the abolition of nebivolol, it is possible to develop a "ricochet" arterial hypertension (withdrawal syndrome).

It is impossible to exclude the possibility of further reducing myocardial contractility in patients with chronic heart failure.

When used simultaneously with antiarrhythmic drugs of class 1 (quinidine, hydroquinidine, flecainide, disopyramide, lidocaine, mexiletine, propafenone) and with amiodarone it is possible to intensify the negative inogropic effect and prolong the time of excitation in the atria.

With the simultaneous use of nebivolol with cardiac glycosides, atrioventricular conduction may be slowed.

Simultaneous use of nebivolol and funds for general anesthesia can cause suppression of reflex tachycardia and increase the risk of developing arterial hypotension.

Concomitant use of nebivolol and BCCC dihydropyridine series (amlodipine, felodipine, licidipine, nifedipine, nicardipine, increase the risk of developing arterial hypotension. 1 further deterioration of the pumping function of the ventricles in patients with cardiac Mr.insufficiency.

Clinically significant interaction of Nsbivolol and non-steroidal anti-inflammatory drugs (NSAIDs) has not been established.

Acetylsalicylic acid as antiplatelet agent can be used concomitantly with nebivolol.

The simultaneous use of tricyclic antidepressants, barbiturates and phenothiazine derivatives, anxiolytics, hypnotics, ethanol can enhance the antihypertensive effect of nebivolol.

Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. Nevertheless, with the simultaneous use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (palpitation, tachycardia) can be masked.

Contraindicated simultaneous reception with floktafeniyom: nebivolol is capable to prevent compensatory reactions of the cardiovascular system associated with arterial hypotension or shock, which may be caused by floktafeniyom.

Simultaneous reception of nebivolol with baclofen, amifostine leads to an increase in arterial hyposfromtion.

With simultaneous use with sultoiridom there is an increased risk of ventricular arrhythmia of the type "pirouette".

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 sympagomimetics with the presence of both alpha and beta adrenergic effects (the risk of arterial hypotension, severe bradycardia and cardiac blockade).

Simultaneous use of baclofen and amifostine with antihypertensive drugs can cause a significant decrease in blood pressure, therefore, correction of doses of antihypertensive drugs is required.

Theoretically, the combined use of msfloquine with Iebivolol can lead to lengthening of the interval QT.

Pharmacokinetic interaction

When used in combination with anti-invasive drugs serotonin, or other drugs biotransforming with participation isoenzyme CYP2D6 (eg, paroxetine, fluoxetine, thioridazine, quinidine), the concentration of nebivolol in the blood plasma increases, the metabolism of nebivolol slows down, which can lead to the risk of bradycardia and other undesirable effects.

With simultaneous application nebivolol did not affect the pharmacokinetic parameters of digoxin.

When used simultaneously with cymidine, the concentration of iebivolol in the blood plasma increases (there are no data on the effect on the pharmacological effects of the drug). The simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

Rifampicin enhances the metabolism of nebivolol.

With the simultaneous use of nebivolol with nicardipine, concentrations of active substances in the blood plasma increased slightly (which has no clinical significance). With the simultaneous use of nsbivolol and ethanol, furosemide or hydrochlorothiazide, the pharmacokinetic parameters of nebivolol do not change. Not established clinically significant interaction of nebivolol and warfarin.

Special instructions:

Inadmissible abrupt discontinuation of the use of bst-blockers (with a sudden cessation of treatment may develop the syndrome of "withdrawal"), but treatment should be stopped gradually, reducing the dose for 10 days (1-2 weeks in patients with ischemic heart disease).

Treatment of chronic heart failure nsbivolol spend against a background of stable indicatorscardiovascular system, no earlier than 6 weeks after the end of the period of decompensation. Nebivolol can be used to treat chronic heart failure concomitantly with thiazide diuretics, digoxin, ACE inhibitors or angiotensin II receptor antagonists.

With stable angina, the selected dose should provide a heart rate at rest within 55-60 beats / min, with a load of ns greater than 110 beats / min. Beta-adrenergic blockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats / min. Beta-adrenergic blockers should be used with caution in patients with chronic obstructive pulmonary disease, since it is possible to strengthen bronchospasm.

In smoking patients, the effectiveness of beta-blockers is lower.

Nebivolol does not affect the concentration glucose in patients with Diabetes mellitus, however, nebivolol may be masked by signs of hypoglycemia (tachycardia, palpitation) caused by the use of hypoglycemic agents.

Beta-adrenoblockers should be used with caution in patients with increased thyroid function due to the fact that under the influence may be masked clinical signs of gypsyroidism, such as tachycardia.Abrupt withdrawal of the drug may cause an exacerbation of the symptoms of the disease and the development of thyrotoxic crisis. Control of patients taking beta-blockers includes monitoring heart rate and blood pressure (at the beginning of the procedure - every day, then once every 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 time in 4 -5 months.)

The use of psbivolol in patients with pheochromocytoma is possible only with the joint administration of alpha-adrenoblockers.

In elderly patients it is recommended to monitor the kidney function (1 time in 4-5 months). Nebivolol can enhance the symptoms of peripheral circulatory disorders. Beta-adrenoblockers can increase sensitivity to allergens and the severity of anaphylactic reactions. Nebivolol can cause a severe reaction to a number of allergens when administered to patients who have a history of severe anaphylactic reaction to these allergens. Such patients may not respond to the usual doses of epinephrine (adrenaline) used to treat anaphylactic shock.

When deciding whether to prescribe a drug for patients with psoriasis, the expected benefits 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 against the background of treatment with beta-adrenoblockers, tear production can be reduced.

If during the therapy with nebivolol the patient is required to undergo surgery, it is necessary to inform the anesthesia surgeon about the nature of the therapy.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions (risk of dizziness and other side effects).

Form release / dosage:

Tablets 5 mg.

Packaging:

By 7, 10, 14, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 7, 10, 14, 20, 28. 30. 40, 50 or 100 tablets in cans of polyethylene terephthalate or in polymer cans for medicines.

One jar or 1, 2, 3, 4, 5, 8. 9, 10 or 12 contour mesh packages together with the instruction but are placed in a cardboard package.

It is allowed to bundle 2 or 3 cardboard packages (packs) into a group package (shipping container) from cardboard for consumer packaging.

Storage conditions:

In a protected spotlight at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002996

Date of registration:15.05.2015

Expiration Date:15.05.2020

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Bivotenz (Bivotenz)