NEBIVOLOL PILLS 5MG

Mechanism of action

Pharmacotherapeutic group of the drug:

beta 1 - selective blocker

Pharmacological properties

Cardioselective β1- blocker. Nebivolol has a hypotensive, antianginal and antiarrhythmic effect. Reduces high blood pressure (BP) at rest, with physical exertion and stress. Competitively and selectively blocks postsynaptic β1-adrenoreceptors, making them inaccessible to catecholamines, models the release of the 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 β1-adrenoreceptors;

- L-nebivolol has a mild vasodilator 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).

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

By reducing myocardial oxygen demand (decreasing heart rate (HR), reducing 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.

Suction. After ingestion, both enantiomers are rapidly absorbed. Eating does not affect absorption, so nebivolol can be taken regardless of the meal. The bioavailability of ingested nebivolol averages 12% in patients with “fast” metabolism (the effect of “initial passage”) and is almost complete in patients with “slow” metabolism.

Distribution.In blood plasma, both enantiomers are predominantly bound to albumin. Plasma protein binding is 98.1% for D-nebivolol and 97.9% for L-nebivolol.

Inference. Nebivolol is metabolized by alicyclic and aromatic hydrokylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and excreted as O- and N-glucuronides, by the kidneys (38%), through the intestine (48%). T1/2 in patients with “fast” metabolism: hydrocymetabolites - 24 hours, enantiomers of nebivolol - 10 hours; in patients with “slow” metabolism: hydrocymetabolites - 48 hours, nebivolol enantiomers - 30–50 hours. Excretion of unchanged nebivolol through the kidneys is less than 0.5% of the drug dose taken orally.

Given the differences in metabolic rates, the dose of the drug should always be chosen individually: patients with a “slow” metabolism require a smaller dose.

Indications

- arterial hypertension;

- coronary heart disease: prevention of strokes of stress;

- 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 inotropic effects);

- Severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

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

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

- severe bradycardia (heart rate less than 50 beats / min.);

- cardiogenic shock;

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

- metabolic acidosis;

- severe abnormal liver function;

- severe forms of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD);

- severe obliterating diseases of peripheral vessels (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);

- simultaneous reception with flaktafenin, a sultoprid (see the section "Interaction with Other Medicines").

- renal failure;

- diabetes;

- hyperfunction of the thyroid gland;

- burdened allergological history; desensitization therapy, psoriasis;

- BA and COPD;

- atrioventricular block I degree;

- Prinzmetal angina;

- age over 65 years.

Use during pregnancy and lactation

In pregnancy, the drug Nebivolol is prescribed only for vital reasons, when the benefit to the mother exceeds the possible risk to the fetus or newborn (due to the possible development of bradycardia, hypotension, hypoglycemia in the fetus and newborn). If treatment with Nebivolol is necessary, then uteroplacental blood flow and the development and growth of the fetus should be monitored. Treatment must 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.

Nebivolol is excreted in breast milk. If you need to take the drug Nebivolol during lactation, breastfeeding should be stopped.

Special notes

The abolition of β-blockers should be carried out gradually over
10 days (up to 2 weeks in patients with coronary heart disease).

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

In elderly patients, the control of renal function is necessary (1 time per
4-5 months). In case of angina, the dose of the drug should provide a heart rate at rest within 55-60 beats / min., With a load - no more than 110 beats / min.

β-blockers may cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 bpm. (see section "Contraindications").

When deciding on the use of the drug Nebivolol in patients with psoriasis, one should carefully relate the perceived benefits of using the drug and the possible risk of exacerbation of the course of psoriasis.

Patients using contact lenses should take into account that, with the use of β-blockers, it is possible to reduce the production of tear fluid.

When performing surgical interventions, the anesthesiologist should be warned that the patient is taking β-blockers.

Nebivolol does not affect plasma glucose concentration in patients with diabetes mellitus. However, caution should be exercised in treating these patients, since Nebivolol may mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic oral and insulin preparations. Control of plasma glucose concentration should be carried out 1 time per
4-5 months (in patients with diabetes).

With hyperfunction of the thyroid gland, β-blockers may mask tachycardia.

β-blockers should be used with caution in patients with chronic obstructive pulmonary disease, as bronchospasm may increase.

β-blockers can increase the sensitivity to allergens and the severity of Anaphylactic reactions.

In smokers, the effectiveness of β-blockers is lower compared with non-smoking patients.

Influence on ability to drive motor transport and control mechanisms

During the period of treatment with the drug Nebivolol (if any side effects occur), care should be taken when driving vehicles and when engaging in potentially hazardous activities that require increased concentration and psychomotor reactions.

Composition

1 pill contains:

active substance: nebivolol hydrochloride in terms of nebivolol - 5.0 mg;

excipients: lactose monohydrate (milk sugar) - 89.87 mg, pregelatinized starch (1500 starch) - 22.5 mg, sodium cross-carmellose (primellose) - 9.0 mg, povidone (medium molecular weight polyvinylpyrrolidone) - 4.5 mg, microcrystalline cellulose - 17.25 mg, colloidal silicon dioxide (aerosil) - 0.38 mg, Calcium stearate - 1.5 mg.

Dosage and administration

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

The average daily dose for the treatment of hypertension and coronary heart disease is 2.5 mg - 5 mg of the drug Nebivolol (1/2 pill 5 mg - 1 pill 5 mg).

Nebivolol can be used in monotherapy or in combination with other drugs that reduce blood pressure.

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

Treatment of chronic heart failure should begin with a slow increase in dose until an individual optimal maintenance dose is reached. Selection of the dose at the beginning of treatment should be carried out according to the following scheme: keeping at one to two weeks intervals and focusing on the patient's tolerance of this dose: the initial dose is 1.25 mg (1/4 pill 5 mg with a cross-shaped risk) 1 time per day, may be increased first to 2.5-5 mg of the drug Nebivolol (1/2 pill 5 mg - 1 pill 5 mg), and then to 10 mg
(2 tablets 5 mg) 1 time per day.

The maximum daily dose is 10 mg (2 tablets of 5 mg) 1 time per day.

At the beginning of treatment and at each dose increase, the patient should not less
2 hours under the supervision of a physician to ensure that the clinical condition remains stable (especially: blood pressure, heart rate, conduction disturbances, as well as symptoms of worsening of the course of chronic heart failure).

Nebivolol is not recommended for use in patients with severe renal and / or liver failure due to lack of experience.

Side effects

Frequency of side effects: 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%), including individual messages.

Nervous system disorders:

Often: headache, dizziness, fatigue, weakness, paresthesia;

Infrequently: depression, “nightmarish” dreams, confusion, reduced ability to concentrate, drowsiness, insomnia;

Very rarely: fainting, hallucinations.

Violations of the gastrointestinal tract:

Often: dryness of the oral mucosa, nausea, constipation, diarrhea;

Infrequently: dyspepsia, flatulence, vomiting.

Violations of the cardiovascular system:

Uncommon: bradycardia, exacerbation flow CHF, congestive heart failure, retardation of atrioventricular conduction, atrioventricular block, marked decrease in blood pressure, orthostatic hypotension, cardiac arrhythmias, cardialgia, exacerbation "Intermittent" claudication, peripheral edema, Raynaud's syndrome.

Violations of the skin and subcutaneous tissues:

Infrequently: skin erythematous rash, itching;

Very rarely: aggravation of the course of psoriasis, photodermatosis, increased sweating;

In some cases: angioedema.

Violations by the organ of vision:

Infrequently: visual impairment.

Respiratory disorders:

Often: shortness of breath;

Infrequently: bronchospasm, rhinitis.

Reproductive system disorders:

Infrequently: erectile dysfunction.

Other disorders: alopecia.

Drug interaction

Pharmacodynamic interaction

With simultaneous use of β-blockers with blockers of "slow" calcium channels (BMCC) (verapamil and diltiazem), the negative effect on myocardial contractility and AV conductivity is enhanced. It is contraindicated in / in the introduction of Verapamil on the background of the use of nebivolol.

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

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

With simultaneous use of nebivolol with antihypertensive drugs of central action (clonidine, guanfacine, Moxonidine, methyldopa, rilmenidine), heart failure may worsen due to a decrease in sympathetic tone (decrease in heart rate and cardiac output, symptoms of vasodilation). In case of abrupt cancellation of these drugs, especially before the cancellation of nebivolol, the development of ricochet hypertension is possible.

With simultaneous use of nebivolol with class I antiarrhythmic drugs and with Amiodarone, it is possible to enhance the negative inotropic action and lengthen the time of excitation in the atria.

With the simultaneous use of nebivolol with cardiac glycosides, no increase in the effect on the slowing of AV conductivity was found.

The simultaneous use of nebivolol and drugs for general anesthesia can cause the suppression of reflex tachycardia and increase the risk of arterial hypotension.

Clinically significant interaction of nebivolol and nonsteroidal anti-inflammatory drugs (PAP) has not been established.

The simultaneous use of nebivolol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may enhance the hypotensive effect of nebivolol.

The simultaneous use of nebivolol and floctafenin is contraindicated,
as there is a threat of pronounced decrease in blood pressure or shock.

Simultaneous use of nebivolol and sultopride is contraindicated, as the risk of developing ventricular arrhythmia increases, especially in the "pirouette" type.

With the simultaneous use of nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia) can be masked.

When applied simultaneously, sympathomimetic drugs inhibit the activity of nebivolol.

Pharmacokinetic interaction

With simultaneous use of nebivolol with drugs that inhibit serotonin reuptake, or other biotransforming drugs involving the CYP2D6 isoenzyme, nebivolol concentration in plasma increases, nebivolol metabolism slows down, which may lead to the risk of bradycardia.

When used simultaneously with Digoxin, nebivolol does not affect the pharmacokinetic parameters of digoxin.

With the simultaneous use of nebivolol with cimetidine, the concentration of nebivolol in the blood plasma increases.

The simultaneous use of nebivolol and Ranitidine does not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardipine, the concentration of active substances in the blood plasma increases slightly, but this has no clinical significance.

Simultaneous administration of nebivolol and ethanol, Furosemide, or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

No clinically significant interaction between nebivolol and Warfarin has been established.

Symptoms: marked reduction in blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, atrioventricular (AV) blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest, hypoglycemia, convulsions.

Treatment: gastric lavage, taking activated charcoal. In the case of a pronounced decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, in / in the introduction of fluid and vasopressors.In case of bradycardia, it is necessary to inject 0.5-2 mg of atropine intravenously in the absence of a positive effect. A transvenous or intracardiac pacemaker can be used. In case of AV blockade (II-III century), it is recommended intravenous injection of β-adrenostimulants, if they are ineffective, consideration should be given to setting an artificial pacemaker. In heart failure, treatment begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to introduce dopamine, dobutamine or vasodilators. When bronchospasm used intravenous stimulants β2-adrenoreceptors. For ventricular premature beats, Lidocaine (antiarrhythmic agents of class IA should not be administered). When hypoglycemia - intravenous solution of dextrose (glucose), with convulsions - diazepam.

In a dry, dark place, at a temperature not higher than 25 ° C.

Keep out of the reach of children.