Nebilet, tablets 5 mg 14 pcs

Nebilet is antiarrhythmic, hypotensive, antianginal.

Lowering high BP at rest, during physical stress, stress. Competitively and selectively blocks synaptic and extrasynaptic beta1-adrenoreceptors, making them unavailable for catecholamines, modulates the release of endothelial vasodilatory factor (NO). The hypotensive effect is also due to a decrease in the activity of the renin-angiotensin system (does not directly correlate with changes in plasma renin activity).

In the first days of treatment it increases RPS, later on, with long-term use, it is normalized or decreased. Hypotensive effect develops in 2-5 days, stable effect is noted after 1-2 months. It reduces myocardial oxygen demand (lower HR and decrease pre- and post-load), reduces the number and severity of angina attacks and increases exercise tolerance. Antiarrhythmic action is caused by the suppression of pathological heart automatism (including pathological focus) and AV conduction slowing.

Pharmacokinetics

After oral administration it is quickly absorbed from the gastrointestinal tract (food intake has no effect on absorption). Bioavailability – 12% in persons with “fast” (effect of “first passage” through the liver) metabolism and almost full – in persons with “slow”. Protein binding for D-nebivolol – 98.1%, for L-nebivolol – 97.9%.

Metabolized to form active metabolites by acyclic and aromatic hydroxylation and partial N-dealkylation; the resulting hydroxy- and amino derivatives conjugate with glucuronic acid and are excreted as O- and N-glucurones. T1/2 of hydroxymetabolites is 24 h, enantiomers of nebivololol 10 h (for persons with “fast” metabolism); for persons with “slow” – 48 h and 30-50 h, respectively.

Extracted by the kidneys (38%) and intestines (48%).

Indications

Arterial hypertension, IBS.

Active ingredient

Composition

Active ingredients:

Nebivololol hydrochloride micronized 5.45 mg, which corresponds to a nebivololol content of 5 mg.

Associates:

Lactose monohydrate – 141.75 mg,

Corn starch – 46 mg,

croscarmellose sodium – 13.8 mg,

hypromellose 15 mPa×s – 4.6 mg,

Polysorbate 80 – 0.46 mg,

Microcrystalline cellulose – 16.1 mg,

How to take, the dosage

The tablets are taken orally, once a day, preferably always at the same time of the day, regardless of meals, with plenty of fluids.

The average daily dose for the treatment of arterial hypertension and CHD is 2.5-5 mg (1/2-1 tablet). Nebilet® can be used in monotherapy or in combination with other BP-lowering agents.

In patients with renal impairment and in patients over 65 years of age, the recommended starting dose is 2.5 mg (1/2 tablet)/day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tablets of 5 mg at 1 sitting).

The treatment of chronic heart failure should begin with a slow increase in dose until an individual optimal maintenance dose is reached. The dose selection at the beginning of treatment should follow the following pattern, at 1 to 2 week intervals and based on the patient’s tolerance of this dose: a dose of 1.25 mg of nebivolol (1/4 tablet of 5 mg) once daily may be increased first to 2.5-5 mg (1/2 tablet of 5 mg or 1 tablet of 5 mg) and then to 10 mg (2 tablets of 5 mg) once daily.

The maximum daily dose is 10 mg once daily.

The patient should be monitored for at least 2 hours at the start of treatment and each time the dose is increased to make sure that the clinical condition remains stable (especially BP, HR, conduction disturbances, and symptoms of worsening course of chronic heart failure).

Rules for dividing tablets

To divide, place the tablet on a hard, flat surface with the crosshair notched upward and press down on the tablet with both index fingers. To get 1/4 tablet, repeat the same steps with 1/2 tablet.

Interaction

Concomitant use of beta-adrenoblockers with slow calcium channel blockers (verapamil and diltiazem) increases the negative effect on myocardial contractility and AV conduction.

Intravenous administration of verapamil with nebivololol is contraindicated.

The concomitant use of nebivololol with hypotensive agents, nitroglycerin or slow calcium channel blockers may cause severe arterial hypotension (particular caution is required when combined with prazosin).

The concomitant use of nebivololol with class I antiarrhythmic drugs and with amiodarone may increase the negative inotropic effect and prolongation of the excitation time through the atria.

In concomitant use of nebivololol with cardiac glycosides no increased effect on slowing of AV conduction was found.

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

Clinically significant interaction of nebivololol and NSAIDs has not been established.

The concomitant use of nebivololol with tricyclic antidepressants, barbiturates and phenothiazine derivatives may increase the hypotensive effect of nebivolol.

Pharmacokinetic interaction

Concomitant use of nebivololol with drugs that inhibit serotonin reuptake or other agents biotransforming with CYP2D6 isoenzyme increases plasma concentrations of nebivolol, slowing down nebivolol metabolism, 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.

Concomitant use of nebivololol with nicardipine slightly increases plasma concentrations of the active substances, but this has no clinical significance.

The concomitant use of nebivololol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol.

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

In co-administration of nebivololol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia) may be masked.

Special Instructions

The withdrawal of beta-adrenoblockers should be done gradually over 10 days (up to 2 weeks in patients with CHD).

The monitoring of BP and HR at the beginning of the drug should be daily.

In elderly patients, renal function should be monitored (once every 4-5 months).

In patients with angina pectoris, the dose of the drug should provide a resting HR of 55-60 bpm, with an exercise HR of no more than 110 bpm.

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

When considering the use of Nebilet® in patients with psoriasis, the anticipated benefit of the drug must be carefully weighed against the possible risk of exacerbation of psoriasis.

Patients who wear contact lenses should be aware that the use of beta-adrenoblockers may decrease tear fluid production.

In surgical procedures, the anesthesiologist should be advised that the patient is taking beta-adrenoblockers.

Nebivololol has no effect on plasma glucose concentrations in patients with diabetes mellitus. However, caution should be exercised when treating these patients since Nebilet® may mask certain symptoms of hypoglycemia (e.g., tachycardia) caused by the use of hypoglycemic agents for oral administration and insulin. Monitoring of plasma glucose concentrations should be performed once every 4-5 months (in patients with diabetes).

Beta-adrenoblockers may mask tachycardia in cases of thyroid hyperfunction.

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

Beta-adrenoblockers may increase allergen sensitivity and the severity of anaphylactic reactions.

The effect of Nebilet® on the ability to drive and operate vehicles and other mechanisms requiring high concentration

The effect of Nebilet® on the ability to drive vehicles and operate mechanisms has not been specifically studied. Studies of pharmacodynamics of Nebivolol have shown that the drug Nebilet® has no effect on psychomotor function.

When taking Nebilet® (in case of side effects) care should be taken when driving vehicles and engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reaction.

Contraindications

Hypersensitivity, bronchial asthma, heart failure (decompensation stage), severe liver function disorders, arterial hypotension, marked bradycardia, cardiogenic shock, sinus node weakness syndrome, AV blockade of II and III degree, pheochromocytoma, Prinzmetal’s angina pectoris, depression, obliterating peripheral vascular diseases (“intermittent claudication”), myasthenia, muscle weakness, age less than 18 years (effectiveness and safety is not established).

Side effects

CNS and peripheral nervous system: often – headache, dizziness, increased fatigue, weakness, paresthesias; infrequently – depression, nightmares, confusion of consciousness; very rarely – fainting, hallucinations.

The digestive system: frequently – nausea, constipation, diarrhea; infrequently – dyspepsia, flatulence, vomiting.

Cardiovascular system disorders: infrequent – bradycardia, acute heart failure, AV-blockade, orthostatic hypotension, Raynaud’s syndrome.

Skin and subcutaneous tissue: infrequent erythematous skin rash and itching; very rare – aggravation of psoriasis; angioedema in single cases.

Others: infrequent – bronchospasm; rarely – dry eyes.

Overdose

Symptoms: pronounced BP decrease, nausea, vomiting, cyanosis, sinus bradycardia, AV-blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest.

Treatment: Gastric lavage, use activated charcoal. If there is a pronounced decrease in BP, the patient should be placed in a horizontal position with elevated legs, if necessary, IV fluids and vasopressors should be administered.

In bradycardia, 0.5-2 mg of atropine should be administered by IV, if there is no positive effect, transvenous or intracardiac pacemaker can be placed. In AV-blockade (stage II-III) it is recommended to administer beta-adrenergic stimulators, if they are ineffective, the issue of an artificial pacemaker should be considered.

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

In case of bronchospasm, IV β2-adrenoreceptor stimulants are used. In ventricular estrasystole – lidocaine (Class IA antiarrhythmic agents should not be administered).

Pregnancy use

In pregnancy Nebilet® is prescribed only with vital indications when the benefit to the mother exceeds the possible risk to the fetus or newborn (due to possible development of bradycardia, arterial hypotension, hypoglycemia in fetus and newborn).

If Nebilet® treatment is necessary the uterine-placental blood flow and fetal growth should be monitored. The treatment should be discontinued 48-72 h before delivery.

In cases where this is not possible, strict neonatal monitoring should be established for 48-72 h after delivery.

Nebivololol is excreted with the breast milk. If Nebilet® must be taken during lactation, breastfeeding must be discontinued.

Similarities