Nebivir, tablets 5 mg 28 pcs

Cardioselective beta₁-adrenoblocker of III generation with vasodilator properties. The active substance is a racemate consisting of two enantiomers: D-nebivolol and L-nebivolol. D-nebivololol is a competitive and highly selective blocker of β₁-adrenoreceptors; L-nebivololol has a mild vasodilator effect due to modulation of vasodilatory factor (NO) release from vascular endothelium.

Nebivololol decreases HR and BP at rest and at exercise, decreases left ventricular end-diastolic pressure, reduces PEEP, improves diastolic heart function (decreases filling pressure), increases ejection fraction; causes antianginal effect in CHD patients.

The hypotensive effect is also due to decrease of renin-angiotensin system activity (does not directly correlate with changes in plasma renin activity).

The antiarrhythmic action is caused by the suppression of pathological automatism of the heart (including in the pathological focus) and the slowing of AV conduction.

Sustained hypotensive 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.

Pharmacokinetics

After oral administration nebivololol is quickly absorbed from the gastrointestinal tract. Food intake does not affect absorption. Bioavailability is on average 12% in persons with fast metabolism (first-pass effect through the liver) and is almost complete in persons with slow metabolism.

In plasma both enantiomers predominantly bind to albumin. Binding to plasma proteins of D-nebivololol is 98.1%, L-nebivolol is 97.9%.

Metabolized 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-glucuronides.

Extracted by the kidneys (38%) and through the intestine (48%).

In persons with fast metabolism, the T_1/2 of hydroxymetabolites is 24 h, enantiomers of nebivololol 10 h; in persons with slow metabolism: hydroxymetabolites 48 h, enantiomers of nebivololol 30-50 h.

The urinary excretion of unchanged nebivololol is less than 0.5%.

Indications

Active ingredient

Composition

How to take, the dosage

Adults for oral administration – 2.5-5 mg/day in the morning. The optimal effect develops after 1-2 weeks of treatment, and in some cases – after 4 weeks. If necessary, the daily dose is increased to 10 mg/day.

For patients over 65 years of age, the starting dose is 2.5 mg/day. If necessary, the daily dose can be increased to 5 mg.

Interaction

Concomitant use with class I antiarrhythmic drugs, amiodarone may increase the negative inotropic effect and inhibition of AV conduction.

In concomitant use with calcium channel blockers (verapamil and diltiazem) the negative inotropic effect and suppression of AV conduction are increased.

In case of intravenous administration of verapamil with nebivololol, there is a risk of cardiac arrest (concomitant use is contraindicated).

In concomitant use of nebivololol with hypotensive agents, nitroglycerin or slow calcium channel blockers, severe arterial hypotension may occur (special caution is required in combination with prazosin).

Concomitant use with sympathomimetics suppresses the pharmacological activity of nebivololol.

Concomitant use with anesthetic agents may suppress reflex tachycardia and increase the risk of arterial hypotension.

Concomitant use with tricyclic antidepressants, barbiturates, phenothiazine derivatives may increase the antihypertensive effect of nebivolol.

Concomitant use with cimetidine may increase plasma concentrations of nebivololol.

Concomitant use of nebivololol with drugs that inhibit serotonin reuptake or other agents biotransformed with participation of CYP2D6 isoenzyme, increases nebivololol plasma concentrations and slows down metabolism of nebivolol, which may increase the risk of bradycardia.

The symptoms of hypoglycemia (tachycardia) may be masked when nebivololol is coadministered with insulin and oral hypoglycemic agents.

Special Instructions

The therapy should be discontinued gradually (over 1-2 weeks). Decrease of HR up to 55 beats/min requires dose reduction. Against the background of diabetes mellitus it is possible to mask the signs of hypoglycemia, against thyroid hyperfunction – tachycardia. May increase reactions to pollen and other allergens.

It should be withdrawn 24 h before surgical intervention using general anesthesia (including dental surgery) or choose an anesthetic agent with the least negative inotropic effect.

When concomitant administration of antacids is necessary, nebivololol is taken with meals and antacids are taken between meals.

With caution, use during work for drivers of vehicles and people whose profession involves high concentration. It is recommended to avoid alcohol intake during treatment.

Contraindications

Bronchial asthma, decompensated chronic heart failure, untreated pheochromocytoma, severe liver dysfunction, depression, angiospastic angina pectoris (Prinzmetal angina), obliterating peripheral vascular disease (intermittent claudication), hypotension, cardiogenic shock, bradycardia (HR

Side effects

CNS and peripheral nervous system disorders: headache, dizziness, fatigue, paresthesias, depression, decreased ability to concentrate, drowsiness, insomnia, nightmares; very rarely – fainting, hallucinations.

Digestive system disorders: nausea, constipation, diarrhea, dry mouth, flatulence, vomiting.

Cardiovascular system disorders: bradycardia, orthostatic hypotension, dyspnea, edema, acute heart failure, AV blockade, Raynaud’s syndrome, cardialgia.

Skin and subcutaneous tissue disorders: erythematous skin rash, itching; very rarely – worsening of psoriasis.

Allergic reactions: in some cases – angioedema.

Others: bronchospasm, dry eyes.

Similarities