Nebivolol-Vertex, tablets 5 mg 14 pcs
β1 selective adrenoblocker.
Pharmacological properties Pharmacodynamics
Nebivolol is a third-generation cardioselective β1-adrenoblocker with vasodilatory properties. It has antihypertensive, antianginal and antiarrhythmic effects. Nebivolol reduces heart rate (HR) and blood pressure (BP) at rest and during exercise, reduces left ventricular end-diastolic pressure, improving diastolic heart function, reduces total peripheral vascular resistance, increases ejection fraction. Competitively and selectively blocks synaptic and postsynaptic β1 adrenoreceptors, making them inaccessible to catecholamines; modulates the release of endothelial vasodilatory factor nitric oxide (NO).
Nebivololol is a racemate consisting of two enantiomers: SRRR-nebivolol (D-nebivolol) and RSSS-nebivolol (L-nebivolol), combining two pharmacological actions:
– D-nebivololol is a competitive and highly selective blocker of β1 adrenoreceptors;
– L-nebivolol has a vasodilating effect by modulating the release of vasodilatory factor (NO) from the vascular endothelium.
The antihypertensive effect is also due to decrease of renin-angiotensin-aldosterone system (RAAS) activity (does not directly correlate with changes in plasma renin activity).
The antihypertensive effect comes on the 2nd-5th day of treatment, the stable effect is noted after 1-2 months. This effect persists with long-term treatment.
Limiting myocardial oxygen demand (HR slowing down, decreasing ante- and post-loading), nebivololol reduces the number and severity of angina attacks and improves exercise tolerance. Antiarrhythmic action is caused by the suppression of cardiac automatism (including in the pathological focus) and delay of atrioventricular (AV) conduction.
After oral administration, both enantiomers are rapidly absorbed. Food intake has no effect on absorption, so nebivolol can be taken regardless of the time of meals. Bioavailability of ingested nebivolol is on average 12% in patients with “fast” metabolism (“primary passage” effect) and is almost complete in patients with “slow” metabolism.
In plasma both enantiomers are predominantly bound to albumin. Binding to plasma proteins is 98.1% for D-nebivolol and 97.9% for L-nebivolol.
Metabolized with the formation of active metabolites by alicyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy- and amino derivatives conjugate with glucuronic acid and are excreted as O- and N-glucuronides. The rate at which nebivolol metabolism by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the CYP2D6 isoenzyme.
38% of the oral dose of nebivololol is excreted by the kidneys (the amount of unchanged nebivolol is less than 0.5%) and 48% through the intestine.
In patients with “fast” metabolism the half-life (T1/2) of hydroxymetabolites is 24 h, enantiomers of nebivololol – 10 h. In patients with “slow” metabolism T1/2 hydroxymetabolites – 48 h, enantiomers of nebivololol – 30-50 h.
With regard to differences in metabolic rate, the dose of nebivololol should always be adjusted individually: patients with “slow” metabolism require a lower dose.
Pharmacokinetics in special patient groups
Pharmacokinetic parameters have no age or sex differences.
Heart failure, Arrhythmia, Angina pectoris, Tachycardia, Hypertension (high blood pressure), Cardialgia (heart pain)
– Arterial hypertension;
– Coronary heart disease: prevention of angina attacks;
– Chronic heart failure (in combination therapy).
One tablet contains:
the active ingredient:
nebivololol hydrochloride – 5.45 mg (in terms of nebivololol – 5.00 mg);
Lactose monohydrate, 139.91 mg;
Corn starch, 46.00 mg;
Microcrystalline cellulose – 16.10 mg;
croscarmellose sodium – 13.80 mg;
Hyprolose (hydroxypropyl cellulose) – 4.60 mg;
Polysorbate 80 – 2.30 mg;
magnesium stearate – 1.15 mg;
colloidal silicon dioxide – 0.69 mg.
How to take, the dosage
Nebivolol tablets are taken orally, once daily, preferably at the same time, regardless of the time of meals, without chewing and with plenty of fluid.
Arterial hypertension and coronary heart disease
The average daily dose is 2.5-5 mg nebivolol (1/2 tablet 5 mg – l tablet 5 mg) once daily. Clinically significant effect is observed 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 combined therapy.
If necessary, the daily dose can be increased to 10 mg (2 tablets of 5 mg at a time).
The maximum daily dose is 10 mg.
In patients with renal impairment (CKD greater than 20 mL/min), and in patients over 65 years of age, the recommended starting dose is 2.5 mg (1/2 tablet 5 mg) of nebivololol per day. If necessary, the daily dose can be increased to 5 mg (1 tablet of 5 mg).
Cronic Heart Failure (CHF)
The treatment of CHF should begin with a gradual increase in dose until an individual optimal maintenance dose is reached. The dose selection at the start of treatment should be done in stages at one to two week intervals and is based on patient tolerance of the dose, as follows: the initial dose is 1.25 mg nebivolol (1/4 tablet of 5 mg – other dosage forms of nebivolol are available: 5 mg cross-ribbed tablets) once daily, can be increased first to 2.5-5 mg nebivolol (1/2 tablet 5 mg – l tablet 5 mg) once daily, and then to 10 mg (2 tablets of 5 mg in one dose) once daily.
The maximum daily dose is 10 mg (2 5 mg tablets) once daily.
At the start of treatment and each time the dose is increased, the patient should be monitored by a physician for at least 2 hours to confirm that the clinical condition remains stable.
At the time of dose adjustment, regular monitoring of BP, HR, and symptoms of CHF severity is recommended.
When adjusting the dose, if the CHF course worsens or if the drug is intolerant, it is recommended that the dose of the drug be decreased or, if necessary, the drug be stopped immediately (if there is significant arterial hypotension, if the CHF course worsens with acute pulmonary edema, if cardiogenic shock, symptomatic bradycardia, or AV blockade develops).
The treatment with nebivololol should not be stopped abruptly (unless necessary), as this may lead to transient worsening of CHF course. The dose should be reduced gradually (by half weekly, if necessary).
For patients receiving drug therapy for cardiovascular disease, including diuretics, digoxin, angiotensin-converting enzyme inhibitors and/or angiotensin II receptor antagonists, the dose of these drugs should be stabilized for the last two weeks before starting nebivololol treatment.
In patients with mild to moderate renal impairment (CKG greater than 20 ml/min) and in patients over 65 years of age, there is no need to adjust the dose because the dose should be adjusted individually, gradually increasing to the maximum tolerable dose.
There is no experience with nebivololol in patients with severe renal impairment (CKR less than 20 mL/min), so it is not recommended in these patients.
The concomitant use of nebivolol and floktafenine is contraindicated due to the risk of severe arterial hypotension or shock.
The concomitant use of nebivolol and sultopride is contraindicated because of the increased risk of ventricular arrhythmias, especially pirouette-type ventricular tachycardia.
The simultaneous use of β-adrenoblockers with “slow” calcium channel blockers (CMBs) (verapamil and diltiazem) increases the negative effect on myocardial contractility and AV conduction. Intravenous administration of verapamil with nebivolol is contraindicated.
The concomitant use of nebivololol and dihydropyridine type BMCCs (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrandipine) may increase the risk of arterial hypotension. An increased risk of further reduction of myocardial contractility in patients with heart failure cannot be excluded.
The concomitant use of nebivololol with hypotensive agents, nitroglycerin or BMCCs may cause severe arterial hypotension (particular caution is required when combined with prazosin).
The concomitant use of baclofen and amifostine with hypotensive drugs may cause a significant decrease in BP; therefore, correction of the dose of hypotensive drugs is required.
The concomitant use of nebivololol with hypotensive drugs of central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of heart failure due to reduction of sympathetic tone (reduced HR and cardiac output, vasodilation symptoms). In case of abrupt withdrawal of these drugs, especially prior to nebivolol withdrawal, the development of “ricochet” arterial hypertension is possible.
Concomitant use of nebivololol with class I antiarrhythmic drugs (quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone) and with amiodarone may increase the negative inotropic effect and prolong excitation time through atria.
The concomitant use of nebivololol with cardiac glycosides may cause delayed AV conduction. However, according to the results of clinical studies of nebivolol, there are no indications of this interaction.
The concomitant use of nebivololol and drugs for general anesthesia may inhibit reflex tachycardia and increase the risk of arterial hypotension.
A clinically significant interaction of nebivololol and nonsteroidal anti-inflammatory drugs has not been established.
Acetylsalicylic acid as an antiplatelet agent can be used simultaneously with nebivololol.
The concomitant use of nebivololol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the antihypertensive effect of nebivolol.
Concomitant use of nebivololol with insulin and hypoglycemic agents
in oral agents may mask symptoms of hypoglycemia (tachycardia, palpitations).
In concomitant use, sympathomimetic agents inhibit the activity of nebivololol.
. Concomitant use of nebivololol with drugs that inhibit serotonin reuptake or other drugs biotransformed with participation of CYP2D6 isoenzyme (e.g., paroxetine, fluoxetine, thioridazine, quinidine) increases the plasma concentration of nebivololol, nebivololol metabolism is slowed, which may lead to risk of bradycardia.
In concomitant use with digoxin, nebivololol has no effect on the pharmacokinetic parameters of digoxin.
Concomitant use of nebivololol with cimetidine increases plasma concentrations of nebivolol.
The concomitant use of nebivololol and ranitidine has no effect on the pharmacokinetic parameters of nebivololol.
Rifampicin increases the metabolism of nebivololol.
Concomitant use of nebivololol and nicardipine slightly increases plasma concentrations of both substances without changing the clinical effect.
The concomitant use of nebivololol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetic parameters of nebivolol.
No clinically significant interaction between nebivololol and warfarin has been established.
Abrupt discontinuation of β-adrenoblockers is unacceptable; β-adrenoblockers should be withdrawn gradually over 10 days (up to 2 weeks in patients with coronary heart disease).
The monitoring of BP and HR at the beginning of nebivololol administration should be daily.
In elderly patients, monitoring of renal function is necessary (once every 4-5 months).
In patients with angina pectoris, the dose of nebivololol should provide a resting HR of 55-60 bpm and no more than 110 bpm on exertion.
The β-adrenoblockers can cause bradycardia: the dose of nebivololol should be reduced if the HR is less than 50-55 bpm (see Contraindications).
In deciding whether to use nebivololol in patients with psoriasis, the anticipated benefit of the drug must be carefully weighed against the possible risk of exacerbation of the psoriasis.
Patients who wear contact lenses should be aware that the use of β-adrenoblockers may decrease tear fluid production.
In surgical procedures, the anesthesiologist should be advised that the patient is taking β-adrenoblockers.
Nebivololol has no effect on plasma glucose concentrations in patients with diabetes mellitus. However, caution should be exercised when treating these patients since nebivolol may mask certain symptoms of hypoglycemia (tachycardia, palpitations) caused by the use of hypoglycemic agents for oral administration and insulin. In patients with diabetes, monitoring of plasma glucose concentrations should be performed once every 4-5 months.
In thyroid hyperfunction, β-adrenoblockers may mask tachycardia.
The β-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease because bronchospasm may increase.
Nebivololol may increase symptoms of peripheral circulatory disorders.
β-adrenoblockers may increase allergen sensitivity and the severity of anaphylactic reactions. Nebivolol may cause severe reactions to a number of allergens when prescribed to patients who have a history of severe anaphylactic reactions to these allergens. These patients may not respond to the usual doses of epinephrine (adrenaline) used to treat anaphylactic shock.
The effectiveness of β-adrenoblockers is lower in smokers than in nonsmokers.
Influence on ability to drive vehicles and mechanisms The effect of nebivololol on ability to drive vehicles and mechanisms has not been studied. During treatment with nebivolol (in case side effects occur) care should be taken with driving vehicles and operating machinery as well as during potentially dangerous activities requiring increased concentration and quick psychomotor reactions.
Circular, flat cylindrical tablets, white or almost white, with a bevel and a rib.
– hypersensitivity to nebivololol or any of the drug components and other β-adrenoblockers;
– acute heart failure;
– Chronic decompensated heart failure (requiring intravenous infusion of drugs with inotropic action);
– severe arterial hypotension (systolic BP less than 90 mm Hg). Hg).);
– sinus node weakness syndrome, including sinoauricular blockade;
– AV blockade of II and III degree (in absence of artificial pacemaker);
– severe bradycardia (HR less than 50 bpm);
– cardiogenic shock;
– pheochromocytoma (without concomitant use of α-adrenoblockers);
– metabolic acidosis;
– severe hepatic dysfunction;
– A history of bronchial asthma and bronchospasm;
– severe peripheral circulatory disorders (“intermittent” claudication, Raynaud’s syndrome);
– myasthenia gravis, muscle weakness;
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
– age less than 18 years (effectiveness and safety not established);
– concomitant use with floktafenine, sultopride (see “Interaction with other drugs”).
– intravenous verapamil administration with nebivololol;
– severe renal failure (creatinine clearance (CK) less than 20 ml/min).
– mild to moderate peripheral circulatory disorders;
– Renal dysfunction (CKG greater than 20 ml/min);
– Diabetes mellitus;
– Thyroid hyperfunction;
– History of allergology, history of desensitization, psoriasis;
– Chronic obstructive pulmonary disease;
– AV block of degree I;
– Prinzmetal angina;
– Age older than 65 years.
Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO):
very often > 1/10;
often from > 1/100 to < 1/10;
infrequently from > 1/1000 to < 1/100;
rarely from > 1/10000 to < 1/1000;
very rarely < 1/10000, including individual reports;
frequency is unknown – it is not possible to determine the frequency of occurrence from the available data.
Nervous system side:
often – headache, dizziness, increased fatigue, weakness, paresthesia;
infrequent – depression, “nightmare” dreams, confusion, decreased ability to concentrate, drowsiness, insomnia;
very rarely – fainting, hallucinations.
often – nausea, constipation, diarrhea, dry oral mucosa; infrequent – dyspepsia, flatulence, vomiting.
frequently – peripheral edema;
infrequently – bradycardia, acute heart failure, aggravation of the course of chronic heart failure, AV blockade, slowed AV conduction, BP decrease, orthostatic hypotension, heart rhythm disturbances, cardialgia, exacerbation of “intermittent” claudication, Raynaud syndrome.
infrequent – erythematous skin rash, skin itching;
very rare – aggravation of the course of psoriasis, photodermatosis, increased sweating; frequency unknown – urticaria.
frequency unknown – angioedema, hypersensitivity.
often – shortness of breath;
infrequently – bronchospasm (including in the absence of obstructive lung disease in the history), rhinitis.
Reproductive system disorders:
infrequent – erectile dysfunction.
infrequent – visual impairment, “dry” eyes.
frequency unknown – alopecia.
Performed BP decrease, nausea, vomiting, cyanosis, marked bradycardia, AV blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, acute heart failure, cardiac arrest, hypoglycemia, seizures.
Gastric lavage, administration of activated charcoal. If BP is significantly decreased, the patient should be placed in a horizontal position with elevated legs, and if necessary, intravenous fluid and vasopressors should be administered. In bradycardia 0.5-2 mg of atropine should be administered intravenously, in the absence of a positive effect a transvenous or intracardiac pacemaker may be placed. In degree II-III AV blockade, intravenous injection of β-adrenomimetics is recommended; if they are ineffective, an artificial pacemaker should be considered. In cardiac insufficiency, treatment shall be started with introduction of cardiac glycosides and diuretics, in the absence of effect it is advisable to introduce dopamine, dobutamine or vasodilators. For bronchospasm, intravenous β2-adrenomimetics are used. In ventricular extrasystole, lidocaine (Class IA antiarrhythmic agents should not be administered). In hypoglycemia – intravenous dextrose (glucose) solution, in convulsions – intravenous diazepam.
. In pregnancy, nebivololol is administered only under strict indications when the benefit to the mother exceeds the risk to the fetus (due to the possibility of delayed fetal development and growth, intrauterine fetal death, preterm delivery, and the development of bradycardia, BP decrease, hypoglycemia and respiratory paralysis in the newborn). Treatment should be interrupted 48-72 hours before delivery. Where this is not possible, uteroplacental blood flow and fetal growth should be monitored, and the newborn should be closely monitored for the first three days after delivery.
Animal studies have shown that nebivololol is excreted with breast milk. If it is necessary to take the drug while breastfeeding, breastfeeding must be stopped.
Nebilet, Binelol, Nebilong, Nebivolol, Nebivolol-Teva, Nebivator, Nebivololol-SZ
3 years. Do not use after the expiration date.
|Conditions of storage|
Store in a light-protected place at a temperature not exceeding 25 ºC. Keep out of the reach of children.
Buy Nebivolol-Vertex, tablets 5 mg 14 pcs with delivery to USA, UK, Europe and over 120 other countries.