Nebivolol-Teva, tablets 5 mg 28 pcs

Indications

Active ingredient

Composition

One tablet contains: the active ingredient nebivololol hydrochloride – 5.45 mg, corresponding to 5 mg of nebivolol; excipients: silica colloidal dioxide – 0.65 mg, magnesium stearate – 2.00 mg, croscarmellose sodium – 11.50 mg, macrogol 6000 – 20.00 mg, lactose monohydrate – 192.40 mg.

How to take, the dosage

Tablets of Nebivolol-Teva should be taken orally, once a day, preferably at the same time, regardless of the time of meals, without chewing and with plenty of fluid.

Arterial hypertension

The average daily dose for the treatment of arterial hypertension is 5 mg nebivolol (1 tablet). Antihypertensive effect develops after 1-2 weeks, and in some cases optimal effect is achieved only after 4 weeks.

The drug may be used in monotherapy or as part of combined therapy in combination with other BP-lowering agents. So far, additional antihypertensive effect has been observed only when combining Nebivololol-Tava, 5 mg with 12.5-25 mg of hydrochlorothiazide.

Patients with renal impairment

The recommended starting dose in patients with renal impairment is 2.5 mg nebivololol daily (1/2 tablet). If necessary, the daily dose can be increased to 5 mg (1 tablet once).

Patients with hepatic impairment

The data on the use of the drug in patients with hepatic impairment or impaired liver function are limited. Therefore, the use of the drug in these patients is contraindicated.

Elderly patients

In patients over 65 years of age, the recommended starting dose is 2.5 mg of nebivolol (½ tablet) daily. If necessary, the dose may be increased to 5 mg nebivolol (1 tablet). However, given the lack of experience in using the drug in patients over 75 years of age, caution should be exercised and such patients should be carefully evaluated.

Cronic Heart Failure

. Treatment of stable CHF should begin with a gradual increase in the dose of nebivolol until an individual optimal maintenance dose is reached. Patients with CHF at initiation of treatment with nebivololol should not have episodes of acute heart failure within the last 6 weeks. The attending physician should have sufficient experience in treating patients with CHF.

In patients receiving therapy with cardiovascular drugs, including diuretics and/or digoxin and/or ACE inhibitors and/or angiotensin II receptor antagonists, the optimal doses of these medications should be adjusted within 2 weeks before starting therapy with nebivololol.

At the start of therapy, the dose of the drug should be adjusted gradually, with one to two weeks between each subsequent dose increase, depending on patient tolerance of each dose. Dose selection should follow the following pattern: a dose of 1.25 mg nebivolol (1/4 tablet) once daily may be increased first to 2.5 to 5 mg nebivolol (1/2 tablet or 1 tablet) once daily and then to 10 mg nebivolol (2 tablets) once daily.

The maximum daily dose is 10 mg nebivololol.

At the start of treatment and with each subsequent dose increase, the patient should be monitored for at least 2 hours to make sure that the clinical condition remains stable (especially: BP, HR, no conduction abnormalities and no symptoms of decompensation of the CHF).

Because of side effects, not all patients are able to achieve the maximum recommended dose of nebivololol. If necessary, the dose already achieved can be reduced in steps and, if possible, returned to it.

When titrating the dose of nebivololol, if the course of CHF worsens or if the drug is intolerant, it is recommended that the dose of nebivolol be initially reduced or if necessary (if severe arterial hypotension, progression of heart failure symptoms with development of acute pulmonary edema, cardiogenic shock, symptomatic bradycardia or AB blockage occur), immediately discontinue it.

The treatment with nebivololol for stable CHF is usually long-term.

A abrupt withdrawal of nebivololol therapy is not recommended, as it may worsen the course of heart failure. If abolition of the drug is necessary, the dose should be reduced in stages, reducing it in half at one-week intervals.

Patients with renal impairment

Special dose adjustments in patients with mild to moderate renal impairment (glomerular filtration rate (GFR) 89-30 ml/min/1.73 m2 body surface area) is not required, since titration to the maximum tolerated dose is individualized. There is no experience of using the drug in patients with severe renal insufficiency (glomerular filtration rate (GFR < 30 ml/min/1.73 m2 body surface area). Therefore, the use of nebivolol is not recommended in these patients.

Patients with hepatic impairment

The data on the use of the drug in patients with hepatic impairment or impaired liver function are limited. Therefore, the use of the drug in these patients is contraindicated.

Elderly patients

There is no need for special dose adjustment in this age group, since titration to the maximum tolerated dose is individualized.

Interaction

Pharmacodynamic interactions

Contraindicated combinations

Floktafenin

Beta-adrenoblockers may interfere with compensatory cardiovascular responses in response to arterial hypotension or shock, which may be caused by floktafenin.

Sultopride

Nebivololol should not be administered concomitantly with sultopride because of the increased risk of ventricular arrhythmias, particularly polymorphic pirouette-type ventricular tachycardia.

Unrecommended combinations

When using nebivolol with class I antiarrhythmic agents (e.g., quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone) prolongation of atrioventricular conduction time and enhancement of negative inotropic effect are possible.

The simultaneous use of beta-adrenoblockers with slow calcium channel blockers (e.g., verapamil, diltiazem) increases the negative effect on contractility and AV conduction. Intravenous administration of verapamil simultaneously with a beta-adrenoblocker may lead to severe arterial hypotension and AV blockade.

Concomitant use with hypotensive agents of central action (e.g., clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) may worsen the course of CHF by reducing the central sympathetic tone (reduced HR and cardiac output, vasodilation). Abrupt withdrawal, especially in case of previous failure of therapy with beta-blockers may increase the risk of developing “ricochet” arterial hypertension.

Combinations to be used with caution

When using nebivololol simultaneously with antiarrhythmic agents of class III (e.g., amiodarone), prolongation of AV lead time may be observed. Concomitant use of nebivolol and drugs drugs for general anesthesia may inhibit reflex tachycardia and increase the risk of arterial hypotension. The general rule is to avoid abrupt withdrawal of beta-adrenoblockers. The anesthesiologist should be informed if the patient is taking nebivolol.

In concomitant use of nebivololol with insulin and hypoglycemic agents for oral administration, nebivololol has no effect on glucose concentration, but may mask the symptoms of hypoglycemia (feeling of “palpitation”, tachycardia).

The concomitant use of nebivololol with baclofen (muscle relaxant) and amifostine (antineoplastic drug) may decrease blood pressure, which requires appropriate adjustment of nebivololol dose.

Combinations to consider

The simultaneous use of nebivolol and heart glycosides may increase AV lead time. There are no data on the presence of interaction between the two drugs in clinical studies. Nebivolol does not affect the pharmacokinetics of digoxin.

The concomitant use of nebivololol with dihydropyridine series BMCCs (e.g., amlodipine. felodipine, lacidipine. nifedipine, nicardipine, nimodipine, nitrandipine) may increase the risk of hypotension and decrease left ventricular contractility in patients with CHF.

The simultaneous use of nebivololol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the antihypertensive effect (additive effect).

Non-steroidal anti-inflammatory drugs (NSAIDs) do not affect the antihypertensive effect of nebivololol.

Sympathomimetic agents may decrease the effectiveness of beta-adrenoblockers. Beta-adrenomimetics may lead to unrestricted alpha-adrenergic activity of sympathomimetic agents with alpha- and beta-adrenergic effects (risk of arterial hypertension, severe bradycardia and cardiac arrest).

Pharmacokinetic interaction

When using nebivololol simultaneously with

Special Instructions

Cessation of therapy or “withdrawal syndrome”

No abrupt termination of treatment with nebivololol should be necessary. Special caution should be exercised when discontinuing therapy in patients with CHD, as exacerbation of angina attacks, myocardial infarction and ventricular arrhythmias have been noted in patients with CHD when beta-adrenoblockers are stopped suddenly. If discontinuation of treatment is necessary, the dose of nebivolol should be reduced gradually over 1-2 weeks. In case of significant aggravation of angina or development of acute coronary syndrome, nebivolol should be temporarily resumed.

Cardiovascular diseases

The monitoring of BP and HR at the beginning of taking the drug should be daily. Like other beta-adrenoblockers, nebivolol may cause prolongation of the PQ interval on ECG. Nebivolol should be used with caution in patients with grade I atrioventricular block, cardiac conduction disorders, history of syncope. Concomitant use of nebivolol with drugs capable of prolonging the PQ interval on ECG is possible only if the expected benefit to the patient outweighs the possible risk of development or aggravation of cardiac conduction abnormalities.

Vasospastic angina (Prinzmetal angina)

. Non-selective beta-adrenoblockers may increase the frequency and duration of angina attacks in patients with vasospastic angina (Prinzmetal’s angina), due to alpha-receptor-mediated coronary artery vasoconstriction. Cardioselective beta1-adrenoblockers should be used with caution in vasospastic angina.

Bradycardia

Beta-adrenoblockers may cause bradycardia. If the resting HR is less than 50-55 bpm, the dose should be reduced or nebivololol should be discontinued.

Peripheral vascular disease

Caution is required when using nebivololol in patients with peripheral vascular disease (including Raynaud’s syndrome) because beta-adrenoblockers may increase symptoms of arterial insufficiency.

Decompensated CHF

Beta-adrenoblockers should not be used in decompensated CHF until the patient is stabilized. Nebivolol can be used concomitantly with thiazide diuretics, digoxin, ACE inhibitors or angiotensin II receptor antagonists (ARA II) to treat mild to moderate stable CHF.

Chronic obstructive pulmonary disease (COPD)

Patients with bronchospastic disease may be prescribed cardioselective beta1-adrenoblockers if other hypotensive agents are intolerant and/or ineffective.

Beta-adrenoblockers should be used with caution in patients with chronic obstructive pulmonary disease because bronchospasm may increase. Patients with a predisposition to bronchospasm when taking beta-adrenoblockers may develop dyspnea as a result of increased airway resistance. It is necessary to closely monitor such patients at the beginning of treatment and when increasing the dose of the drug, as well as to reduce the dose of nebivolol when the initial signs of bronchospasm appear. Before initiating treatment, it is recommended to conduct a study of external respiratory function in patients with a history of bronchopulmonary disease.

The effectiveness of beta-adrenoblockers is lower in smokers than in non-smokers.

Diabetes

Nebivololol does not affect plasma glucose concentrations in patients with diabetes. However, caution should be exercised when treating these patients as nebivololol may mask certain symptoms of hypoglycemia (e.g., tachycardia) caused by use of oral hypoglycemic agents and insulin.

In patients with a labile course of diabetes mellitus with a history of spontaneous hypoglycemia episodes, the use of beta-adrenoblockers may lead to poorer glycemic control and longer recovery time after hypoglycemia. In such a case, it may be necessary to adjust the dose of hypoglycemic agents for oral administration and insulin. This effect usually occurred during treatment with non-selective beta-adrenoblockers and is less likely with cardioselective beta1-adrenoblockers (such as nebivolol).

Thyrotoxicosis

In thyroid hyperfunction, beta-adrenoblockers may mask tachycardia and reduce the severity of thyrotoxicosis symptoms. Abrupt withdrawal of the drug may cause exacerbation of symptoms of the disease and development of thyrotoxic crisis.

Pheochromocytoma

Patients with pheochromocytoma should be prescribed an alpha-adrenoblocker before starting any beta-adrenoblocker (including nebivolol).

General surgical interventions and general anesthesia

When surgical interventions are required, the anesthesiologist should be advised that the patient is taking beta-adrenoblockers (risk of drug interactions with development of bradyarrhythmias and arterial hypotension). Against the background of taking nebivolol, caution should be exercised when using agents for anesthesia that inhibit myocardial contractility. For general anesthesia the use of drugs with minimal negative inotropic effect is recommended.

It is recommended that nebivololol should not be discontinued unnecessarily in the perioperative period (because beta-adrenoreceptor blockade reduces the risk of arrhythmias during induction and tracheal intubation). If it is necessary to interrupt treatment with nebivolol before surgical intervention, the drug should be discontinued at least 24 hours prior to surgery.

Sensitivity reactions

Beta-adrenoblockers may increase sensitivity to allergens and the severity of anaphylactic/hypersensitivity reactions. Administration of normal therapeutic doses of epinephrine (adrenaline) with beta-adrenoblockers does not always lead to the desired clinical effect. Thus, caution should be exercised when prescribing beta-adrenoblockers to patients with a history of severe hypersensitivity reactions or undergoing desensitization.

Psoriasis

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 course.

Contact lenses

Patients who wear contact lenses should be aware that the use of beta-adrenoblockers may decrease tear fluid production. Preclinical studies using standard techniques showed no genotoxic and carcinogenic effects in humans.

Influence on the ability to drive vehicles and mechanisms

. During the treatment with Nebivolol-Teva patients should be careful when driving vehicles, operating machinery and performing potentially dangerous activities which require increased concentration and quick psychomotor reactions due to the possibility of side effects such as dizziness and increased fatigability.

Synopsis

Contraindications

Side effects

The frequency of side effects is given in accordance with the classification of the World Health Organization: very frequently (more than 10%), frequently (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 available data it was impossible to determine the frequency of occurrence).

Disorders of the immune system: frequency unknown – angioedema, hypersensitivity.

Mental disorders: infrequent – depression, “nightmares” dreams.

Nervous system disorders: frequent – headache, dizziness, paresthesia; very rare – fainting.

Visual organ disorders: infrequently – visual impairment.

Cardiac disorders: infrequent – bradycardia, heart failure, slowed AV conduction.

Vascular disorders:infrequent – marked decrease in BP, worsening of claudication.

Disorders of the respiratory system, thorax and mediastinum: often – shortness of breath; infrequently – bronchospasm.

Gastrointestinal tract disorders:often – nausea, constipation, diarrhea; infrequently – dyspepsia, flatulence, vomiting.

Skin and subcutaneous tissue disorders: infrequent – skin itching; erythematous skin rash; very rare – aggravation of the course of psoriasis; frequency unknown – urticaria.

Gender and mammary gland disorders: infrequent – erectile dysfunction.

General disorders and disorders at the site of administration: frequent – increased fatigue, edema.

The following adverse reactions may occur with some beta-adrenoblockers: psychosis, hallucinations, confusion, cold/cyanosis of the extremities, Raynaud’s syndrome, “dry eye” syndrome, oculo-mucosal syndrome by practolol type.

Chronic heart failure

The most common adverse reactions to nebivololol therapy are bradycardia and dizziness, which occurred in 11% of patients. Other adverse reactions possibly associated with nebivolol treatment of CHF: decompensation of CHF, orthostatic hypotension, drug intolerance, 1st degree AV blockade, edema of lower extremities.

Overdose

There are no data on overdose of the drug.

Symptoms of beta-adrenoblocker overdose: marked BP decrease, sinus bradycardia, bronchospasm and acute heart failure.

Treatment

In case of overdose or development of a hypersensitivity reaction, the patient should be monitored continuously in the intensive care unit. Monitoring of plasma glucose concentration is recommended. Gastric lavage, administration of activated charcoal and laxatives are required to prevent further absorption of the drug from the gastrointestinal tract. Artificial lung ventilation may be required.

In case of bradycardia or marked vagotonia, 0.5-2 mg of atropine should be given intravenously (IV). In AV-blockade (stage II-III) it is recommended to administer beta-adrenomimetics intravenously, and if they are ineffective, the installation of a pacemaker should be considered. With a marked decrease in BP and shock is recommended intravenous administration of plasma substitute solutions and, if necessary, catecholamines. In the absence of the desired effect – intravenous glucagon at a rate of 50-100 mcg/kg body weight. In cardiac insufficiency, treatment begins with administration of cardiac glycosides and diuretics; if there is no effect, it is advisable to administer dopamine, dobutamine or vasodilators. For bronchospasm, bronchodilators such as inhaled beta2-adrenomimetics short-acting and/or aminophylline are used. Nebivolol will probably not be excreted by hemodialysis due to its high degree of binding to plasma proteins.

Pregnancy use

Similarities