Nebivolol, tablets 5 mg 28 pcs

Indications

Active ingredient

Composition

1 tablet contains:

Active ingredients:

nebivololol hydrochloride 5.45 mg, which corresponds to the content of nebivololol 5 mg

Associates:

Lactose monohydrate – 139.91 g,

Corn starch – 46 mg,

Microcrystalline cellulose – 16.1 mg,

croscarmellose sodium – 13.8 mg,

hyprolose (hydroxypropyl cellulose) – 4.6 mg,

polysorbate 80 – 2.3 mg,

magnesium stearate – 1.15 mg,

colloidal silicon dioxide – 0.69 mg.

How to take, the dosage

Overly, at the same time, regardless of the time of eating, without chewing and with plenty of fluid.

The 5 mg or 10 mg tablet can be divided into two or four equal parts in a crisscross pattern.

Arterial hypertension and coronary heart disease

The average daily dose is 2.5-5 mg (1-2 tablets of 2.5 mg; 1/2-1 tablet of 5 mg) once daily.

The optimal antihypertensive effect is achieved after 1-2 weeks of treatment, in some cases after 4 weeks.

If necessary, the dose may be increased to a maximum daily dose of 10 mg. Nebivolol in monotherapy or in combination with other hypotensive agents is possible.

Elderly patients: for patients over 65 years of age, the starting dose is 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg). If necessary, the daily dose can be increased to 5 mg.

Because of the limited experience of using the drug in elderly patients, however, caution should be exercised and patients over the age of one should be carefully evaluated.

There is no need for dose adjustment in elderly patients; therefore, the dose should be adjusted individually, increasing gradually to the maximum tolerated dose.

Patients with renal insufficiency (CKR greater than 20 ml/min): the initial dose is 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg). If necessary, the daily dose may be increased to 5 mg. Increasing the dose in such patients should be done with extreme caution.

Chronic heart failure (CHF)

The treatment of stable CHF should be started with a gradual dose increase until an individual optimal maintenance dose is reached. Patients should have no attacks of acute heart failure within last 6 weeks. It is recommended to treat under close medical supervision.

The treatment of CHF with beta-adrenoceptor blockers should be initiated when the patient has been clinically stable for the last 2 weeks.

The dose at the beginning of therapy should be adjusted according to the following scheme, at intervals of 1 to 2 weeks: a dose of 1.25 mg per day (1/2 tablet of 2.5 mg or 1/4 tablet of 5 mg) may be increased first to 2.5 mg per day (1 tablet of 2.5 mg or 1/2 tablet of 5 mg), then to 5-10 mg per day.

Each dose increase should be made at least 1 to 2 weeks later, depending on individual tolerance to the drug.

At the start of treatment and with each dose increase, the patient should be monitored for at least 2 hours to make sure that the clinical condition remains stable (especially: BP, HR, conduction abnormalities, and symptoms of worsening course of chronic heart failure).

The maximum daily dose of nebivololol is 10 mg once daily.

A regular monitoring of BP, HR and symptoms of chronic heart failure is recommended during titration.

When titration is in progression of CHF deterioration or drug intolerance it is recommended to reduce the dose of Nebivolol or, if necessary, to stop it immediately (in case of severe arterial hypotension, in worsening of CHF course with acute pulmonary edema, in case of cardiogenic shock, symptomatic bradycardia or atrioventricular block).

The treatment of stable CHF is generally long-term. Treatment with Nebivolol should not be stopped abruptly (unless necessary), because it may lead to a temporary exacerbation of CHF. If it is necessary to stop the drug, withdrawal is carried out gradually, reducing the dose by half over a week.

Interaction

Pharmacodynamic interaction

The concomitant use of nebivolol and sultopride is contraindicated because of the increased risk of ventricular arrhythmias, especially pirouette-type polymorphic ventricular tachycardia, when they are used simultaneously.

Unrecommended combinations

Combinations to be used with caution

The simultaneous use of nebivolol with insulin and hypoglycemic agents for oral administration may mask the symptoms of hypoglycemia (palpitations, tachycardia).

The concomitant use of nebivolol and drugs for general anesthesia may inhibit reflex tachycardia and increase the risk of arterial hypotension.

The concomitant use of nebivololol with baclofen, amifostine, with hypotensive drugs may cause a significant drop in BP, so correction of doses of hypotensive drugs is required.

Combinations to consider

The concomitant use of nebivololol with cardiac glycosides may delay atrioventricular conduction. Nebivolol does not affect the pharmacokinetic parameters of digoxin.

Concomitant use of nebivololol and dihydropyridine type BMCCs (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) may increase the risk of arterial hypotension. 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 may lead to severe arterial hypotension (special caution is required when combined with prazosin).

The simultaneous use of tricyclic antidepressants, barbiturates and phenothiazine derivatives, anxiolytics, sleeping pills may increase the antihypertensive effect of nebivololol.

Clinically significant interaction of nebivololol and nonsteroidal anti-inflammatory drugs (NSAIDs) was not established. Acetylsalicylic acid as an antiplatelet agent may be used concomitantly with nebivololol. Simultaneous use of sympathomimetic agents may inhibit the activity of beta-adrenoblockers.

Theoretically, co-administration of mefloquine with nebivololol may result in prolongation of the QT interval.

Pharmacokinetic interactions

Concomitant use with cimetidine may increase plasma concentrations of nebivolol (data on the effect on the pharmacological effects of the drug are not available).

The concomitant use of ranitidine had no effect on the pharmacokinetic parameters of nebivololol.

Rifampicin increases the metabolism of nebivololol.

Concomitant use of nebivololol with nicardipine slightly increases plasma concentrations of the active substances without changing the clinical effect.

Concomitant administration of ethanol, furosemide or hydrochlorothiazide has no effect on the pharmacokinetics of nebivololol.

No clinically significant interaction between nebivololol and warfarin has been established.

Special Instructions

The abrupt discontinuation of beta-adrenoblockers is unacceptable (abrupt treatment discontinuation may result in “withdrawal” syndrome), treatment should be stopped gradually if possible, reducing the dose over 10 days (1-2 weeks in patients with coronary heart disease).

The monitoring of patients taking beta-adrenoblockers includes monitoring heart rate and blood pressure (daily at the beginning of therapy, then once every 3-4 months).

In elderly patients, monitoring of renal function is necessary (once every 4-5 months).

In stable angina, the selected dose should provide a resting HR of 55-60 bpm, and not more than 110 bpm during exercise.

Beta-adrenoblockers can cause bradycardia: the dose should be reduced if HR is less than 50-55 bpm. (see Contraindications).

Beta-adrenoblockers should be used with caution in the following patient groups:

– with peripheral circulatory disorders,

– with grade I atrioventricular block, because beta-adrenoblockers adversely affect pulse conduction time;

– with Prinzmetal angina due to unimpeded alpha receptor-mediated coronary artery vasoconstriction: Beta-adrenergic antagonists may increase the number and duration of angina attacks.

Beta-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease because they may increase bronchospasm.

Beta-adrenoblockers should not be used in patients with untreated chronic heart failure until the condition has stabilized.

The treatment of chronic heart failure with nebivololol should not be used until 6 weeks after the end of a period of decompensation, when the cardiovascular system is stable.

Nebivololol can be used concomitantly with thiazide diuretics, digoxin, ACE inhibitors or angiotensin II receptor antagonists for therapy of chronic heart failure.

The efficacy of beta-adrenoblockers is lower in smoking patients than in nonsmoking patients.

Nebivololol has no effect on glucose concentrations in patients with diabetes mellitus; however, signs of hypoglycemia (tachycardia, palpitations) caused by use of hypoglycemic agents may be masked by nebivololol. In diabetic patients, control of glucose concentration should be performed once every 4-5 months.

Beta-adrenoblockers should be used with caution in patients with elevated thyroid function due to the fact that clinical signs of hyperthyroidism, such as tachycardia, may be masked under the influence.

Abrupt withdrawal of the drug may cause exacerbation of symptoms and development of a thyrotoxic crisis.

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

Beta-adrenoblockers can increase allergen sensitivity and the severity of anaphylactic reactions. Nebivolol may cause severe reactions to a number of allergens when administered 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.

When deciding whether to prescribe the drug to patients with psoriasis, the expected benefit of the drug should be carefully weighed against the possible risk of worsening the course of psoriasis.

Patients who wear contact lenses should be aware that treatment with beta-adrenoblockers may decrease tear fluid production.

If a patient requires surgery during therapy with Nebivololol, the surgeon-anesthesiologist must be informed of the nature of the therapy.

Continued beta-adrenoblockade reduces the risk of arrhythmias during anesthesia and intubation. If preparations for surgery involve interruption of beta-adrenoblockade, beta-adrenergic antagonists should be discontinued at least 24 hours before surgery.

Anesthetics that cause myocardial depression should be used with caution.

Vagal reactions in the patient can be prevented by intravenous injection of atropine.

Contraindications

– Hypersensitivity to nebivololol or other components of the drug and other beta-adrenoblockers;

– acute heart failure;

– Chronic decompensated heart failure (requiring intravenous infusion of drugs with inotropic action);

– significant arterial hypotension (systolic blood pressure

Side effects

The frequency of side effects listed below was determined according to the following (World Health Organization classification): very common (more than 10%), common (more than 1% and less than 10%), infrequent (more than 0.1% and less than 1%), rare (more than 0.01% and less than 0.1%), very rare (less than 0.01%), frequency unknown (no data are available to estimate the frequency of development).

Disorders of the immune system:

very rare: angioedema, hypersensitivity.

Psychiatric disorders:

infrequently: depression, “nightmarish” dreams, psychosis;

very rarely: hallucinations, confusion.

Nervous system disorders:

very common: dizziness;

often: headache, dizziness, weakness, paresthesia;

very rare: fainting.

Visual disturbances:

infrequently: visual disturbance;

rarely: dry eyes.

Cardiovascular system disorders:

very common: bradycardia;

often: worsening the course of CHF1, atrioventricular block of degree I, orthostatic hypotension;

infrequent: Peripheral edema, bradycardia, heart failure, delayed atrioventricular conduction/atrioventricular block, marked BP decrease, progression of associated intermittent claudication;

very rarely: Reino syndrome.

Disorders of the respiratory system, thorax and mediastinum:

often: dyspnea;

infrequently: bronchospasm (including in the absence of obstructive lung disease in the history).

Gastrointestinal disorders:

often: nausea, constipation, diarrhea;

infrequently: dyspepsia, flatulence, vomiting.

Gender and mammary gland disorders:

infrequent: erectile dysfunction.

Skin and subcutaneous tissue disorders:

infrequent: erythematous skin rash, itching;

very rare: aggravation of the course of psoriasis, urticaria;

frequency unknown: alopecia.

General disorders and disorders at the site of administration:

often: increased fatigue;

very rarely: coldness/cyanosis of the extremities;

infrequently: photodermatosis, hyperhidrosis.

Overdose

Symptoms: marked BP decrease, marked bradycardia, acute heart failure, atrioventricular block, cardiogenic shock, cardiac arrest, bronchospasm, loss of consciousness, seizures, coma, nausea, vomiting, hypoglycemia, cyanosis.

Treatment: gastric lavage, administration of activated charcoal. In case of marked BP decrease the patient should be given a horizontal position with elevated legs, if necessary, intravenous administration of fluids and vasopressors. Artificial lung ventilation may be necessary.

In case of marked bradycardia, 0.5-2 mg of atropine should be given intravenously; if there is no positive effect, an artificial pacemaker can be placed.

In case of atrioventricular block (stage II-III), intravenous administration of beta-adrenomimetics is recommended. The effect of beta-adrenoblockers can be neutralized by slow intravenous isoprenaline, starting at a dose of 5 µg/min, or dobutamine, starting at a dose of 2.5 µg/min, until the desired effect is achieved. In severe cases, isoprenaline may be combined with dopamine.

If these doses do not produce the desired effect, consideration should be given to an intravenous injection of 50-100 µg/kg glucagon. If necessary, the injection should be repeated after 1 h followed by an intravenous injection of 70 µg/kg/h of glucagon. If they are ineffective, an artificial pacemaker should be considered.

In case of cardiac insufficiency, treatment is started with administration of cardiac glycosides and diuretics; if there is no effect, administration of dopamine, dobutamine or vasodilators is appropriate.

In case of bronchospasm, intravenous beta2-adrenomimetics are used.

In case of seizures, intravenous diazepam.

In case of hypoglycemia, intravenous dextrose (glucose) may be indicated.

Similarities