Nebivolol 5mg pills 5

Tablets of a round, biconvex form from white to white with a yellowish shade of color, with a cruciform risk on one side.

pharmachologic effect

Pharmacotherapeutic group: β1-blocker selective.

ATC code: C07AB12

Pharmacological properties

Pharmacodynamics

Nebivolol is a cardioselective β1-adrenergic blocker, has antihypertensive, antianginal and antiarrhythmic action. Reduces high blood pressure (BP) at rest, with physical exertion and stress. Competitively and selectively blocks postsynaptic β1-adrenoreceptors, making them inaccessible to catecholamines, modulates 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 antihypertensive 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 plasma renin activity).

The antihypertensive effect develops after 2–5 days of regular use of the drug. Sustained antihypertensive 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 cardiac automatism (including in the pathological focus) and the slowing down of atrioventricular conduction.

Pharmacokinetics

Suction

After ingestion is rapidly absorbed from the gastrointestinal tract. Eating does not affect absorption, so nebivolol can be taken regardless of meal times. Bioavailability is about 12% in patients with “fast” metabolism (the effect of “initial passage”) and can be almost complete in patients with “slow” metabolism.

Distribution

In blood plasma, both enantiomers are predominantly bound to albumin.

Binding to plasma proteins for D-nebivolol is 98.1%, for
L-nebivolol - 97.9%.

Metabolism

Nebivolol is metabolized by alicyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and displayed as
O- and N-glucuronides.The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the CYP2D6 isoenzyme. The metabolic rate does not affect the effectiveness of nebivolol.

Removal

Excreted by the kidneys (38%) and through the intestines (48%). The half-life (T1 / 2) in patients with “fast” metabolism: hydroxymetabolites - 24 hours, enantiomers of nebivolol - 10 hours; in patients with “slow” metabolism: hydroxymetabolites -
48 h, nebivolol enantiomers - 30–50 h. The excretion of unchanged nebivolol through the kidneys is less than 0.5% of the oral dose of the drug.

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

• arterial hypertension;
• coronary heart disease: prevention of strokes of stress;
• chronic heart failure (as part of combination therapy).

• hypersensitivity to any 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. Art.);
• sick sinus syndrome, including sinoauricular block;
• atrioventricular block II-III degree (without artificial pacemaker);
• a history of bronchospasm and bronchial asthma;
• pheochromocyte (without the simultaneous use of a-blockers);
• metabolic acidosis;
• bradycardia (heart rate less than 50 beats / min);
• cardiogenic shock;
• severe abnormal liver function;
• severe peripheral circulatory disorders (intermittent claudication, Raynaud's syndrome);
• myasthenia gravis;
• depression;
• simultaneous reception with flaktafenin, sultoprid (see the section "Interaction with other medicines");
• age up to 18 years (efficacy and safety have not been established).

Carefully

Renal failure (creatinine clearance (CC) less than 20 ml / min), abnormal liver function, diabetes mellitus, hyperthyroidism, atrioventricular block I degree, desensitization therapy, psoriasis, allergic diseases in history, chronic obstructive pulmonary disease, impaired peripheral circulation, Prinzmetal angina, over 65 years old.

Pregnancy and Breastfeeding

Nebivolol can have a harmful effect on the course of pregnancy, on the fetus and the newborn. Reduction of placental perfusion under the action of
β-blockers can cause fetal developmental delay, fetal fetal death, miscarriage, and premature birth. Newborns may experience bradycardia, lower blood pressure, hypoglycemia, and respiratory paralysis.Use during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Nebivolol should be discontinued 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict monitoring of newborns within 48-72 hours after delivery.

Animal studies have shown that nebivolol is excreted in milk from lactating animals. If necessary, the use of the drug during lactation breastfeeding should be stopped.

Special notes

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

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

In elderly patients, monitoring of renal function is necessary (1 time in 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 beats / min (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.

During surgical interventions, an 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 in 4-5 months. (diabetic patients).

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-adrenergic blockers is lower compared to non-smoking patients.

Impact on the ability to drive vehicles and other mechanisms

During the period of treatment, care must be taken when driving and occupying other potentially dangerous activities that require high concentration of attention and speed of psychomotor reactions.

1 tablet contains:

Active ingredient: nebivolol hydrochloride - 5.45 mg (in terms of nebivolol -
5.00 mg).

Excipients: Betadex - 23.00 mg; pregelatinized corn starch - 38.40 mg; microcrystalline cellulose - 108.55 mg; Crospovidone - 1.90 mg; colloidal silicon dioxide - 0.90 mg; Magnesium stearate - 1.80 mg.

Inside, preferably at the same time of day, regardless of the meal time, without chewing and drinking plenty of liquid.

Hypertension and Coronary Heart Disease

The average daily dose of nebivolol is 2.5–5 mg 1 time per day. For patients with renal insufficiency and patients over 65 years old, an initial dose of nebivolol 2.5 mg / day is recommended.

If necessary, the daily dose of nebivolol can be increased to 10 mg (in one step). The optimal therapeutic effect becomes pronounced after 1-2 weeks of taking the drug, and in some cases - after 4 weeks. Nebivolol can be used in combination therapy with other drugs that reduce blood pressure.

Chronic heart failure

The dose of nebivolol is selected gradually until an individual optimal maintenance dose is reached. It is necessary to start treatment of chronic heart failure with β-adrenoreceptor blockers in a clinically stable state over the past two weeks.

Treatment begins with a dose of 1.25 mg 1 time per day with a gradual increase (with an interval of at least 2 weeks) to 2.5–5 mg 1 time per day, if necessary up to a maximum dose of 10 mg 1 time per day.The patient should be under the supervision of a physician for 2 hours after taking the first dose of the drug, as well as after each subsequent dose increase. During the selection of the dosing regimen, in case of worsening of the course of chronic heart failure or intolerance of the drug, it is recommended to reduce the dose of nebivolol or stop its administration. Reception of nebivolol is not recommended to stop abruptly (if it is not necessary), since this may lead to a temporary exacerbation of the symptoms of heart failure. If you need to stop taking the drug, the cancellation is carried out gradually, halving the dose weekly.

Patients with a renal failure (KK less than 20 ml / min.)

The initial dose is 2.5 mg / day. If necessary, the daily dose can be increased to 5 mg. In patients with impaired renal function (QC less than 20 ml / min), the dose should be increased with extreme caution.

Elderly patients

For patients older than 65 years, the initial dose is 2.5 mg / day. If necessary, the daily dose can be increased to 5 mg. However, taking into account the limited experience of using the drug in elderly patients, it is necessary to be careful and conduct a thorough examination of patients over the age of 65 years. Elderly patients do not need a dose adjustment, so it is necessary to individually select the dose, gradually increasing it to the maximum tolerated dose.

The frequency of the side effects listed below was determined according to the 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 (according to the available data it is impossible to estimate the frequency of development).

On the part of the immune system: the frequency is unknown - angioedema, hypersensitivity.

On the part of the psyche: infrequently - “nightmarish” dreams, depression; very rarely - hallucinations, psychosis, confusion.

The nervous system: often - headache, dizziness, weakness, paresthesia; very rarely - fainting.

On the part of the organ of vision: the frequency is unknown - impaired vision, dry eyes.

On the part of the gastrointestinal tract: often - nausea, constipation, diarrhea; infrequently - dyspepsia, flatulence, vomiting.

Since the cardiovascular system: very often - bradycardia (in patients with CHF); often - aggravation of CHF, atrioventricular block I degree, orthostatic hypotension; infrequently - bradycardia, heart failure, slowing of atrioventricular conductivity / atrioventricular block, pronounced decrease in blood pressure, progression of concomitant "intermittent" claudication; very rarely - Raynaud's syndrome.

On the part of the skin and subcutaneous tissues: often - edema; infrequently - skin eruption of erythematous character, skin itch; very rarely - aggravation of the course of psoriasis; frequency is unknown - alopecia.

On the part of the respiratory system: often - shortness of breath; infrequently - bronchospasm (including in the absence of obstructive pulmonary disease in history).

Reproductive system: infrequently - erectile dysfunction.

General p