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Active ingredients
Nebivolol
Release form
Pills
Composition
1 tab.: Nebivolol hydrochloride micronized 5.45 mg, which corresponds to the content of nebivolol 5 mg. Adjuvants: 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, colloidal silicon dioxide - 0.69 mg, magnesium stearate - 1.15 mg.
Pharmacological effect
Cardioselective beta1-adrenoblocker. It has a hypotensive, antianginal and antiarrhythmic effect. Reduces increased blood pressure at rest, with physical exertion and stress. Competitively and selectively blocks postsynaptic β1-adrenoreceptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor nitric oxide (NO). Nebivolol is a racemate of two enantiomers: SRRR-nebivolol (D-nebivolol) and RSS-α-nebolol-nebivolomer -RBR-nebivolol (D-nebivolol) and β-nebivolomer-nebivolol. combining two pharmacological actions: - D-nebivolol is a competitive and highly selective blocker of β1-adrenoreceptors; - L-nebivolol has a mild vasodilator effect due to modulation of vazod release edematizing factor (NO) from the vascular endothelium. The hypotensive effect is also due to a decrease in the activity of the renin-angiotensin-aldosterone system (RAAS) (does not directly correlate with changes in plasma renin activity). A stable hypotensive effect develops after 1-2 weeks of regular use of the drug, and in some cases - after 4 weeks, a stable action is noted after 1-2 months. Reducing the need for myocardium in oxygen (a decrease in heart rate and a decrease in preload and afterload) reduces the number and severity of attacks okardii and enhances portability nagruzki.Antiaritmicheskoe physical effect due to suppression of pathological cardiac automaticity (including in the pathological focus) and slowing AV-conduction.
Pharmacokinetics
AbsorptionAfter ingestion, both enantiomers are rapidly absorbed. Eating does not affect absorption, so nebivolol can be taken regardless of the meal. The bioavailability of nebivolol after oral administration averages 12% in people with a fast metabolism (the effect of the first passage through the liver) and is almost complete in people with a slow metabolism. Distribution In blood plasma, both enantiomers are predominantly associated with albumin.Plasma protein binding is 98.1% for D-nebivolol and 97.9% for L-nebivolol. Metabolism Metabolized by acyclic and aromatic hydroxylation and partial N-dealkylation. The resulting hydroxy and amino derivatives are conjugated with glucuronic acid and excreted as O- and N-glucuronides. Excretion is excreted by the kidneys (38%) and through the intestine (48%). In persons with fast T1 / 2 hydroxymetabolite metabolism, 24 h, nebivolol enantiomers 10 h; in persons with slow metabolism: hydroxymetabolites - 48 hours, nebivolol enantiomers - 30-50 hours. Excretion of unchanged nebivolol in urine is less than 0.5% of the amount of the drug ingested.
Indications
- Arterial hypertension; - Ischemic heart disease: prevention of strokes of stress; - Chronic heart failure (as part of combination therapy).
Contraindications
- acute heart failure; - chronic heart failure in the decompensation stage (requiring intravenous administration of drugs with inotropic effects); severe arterial hypotension (systolic blood pressure less than 90 mm Hg); - SSS, including sinoatrial blockade; - AV - blockade II and III degree (without artificial pacemaker); - bradycardia (HR less than 60 beats / min); - cardiogenic shock; - pheochromocytoma (without simultaneous use of alpha-adrenergic blockers); - metabolic acidosis; - pronounced abnormalities in liver function; - bronchospasm and bro history of such asthma; severe oblique peripheral vascular disease (intermittent claudication, Raynaud's syndrome); myasthenia; depression; lactose intolerance, lactase deficiency, and glucose / galactose malabsorption syndrome; children and adolescents under 18 years of age (efficacy and safety not studied); - Hypersensitivity to nebivolol or one of the components of the drug.
Precautionary measures
Do not exceed the recommended dose. With caution, you should use the drug for kidney failure, diabetes, hyperthyroidism, history of allergic diseases, psoriasis, chronic obstructive pulmonary disease, AV-blockade I degree, Prinzmetal angina, as well as patients over the age of 75 .
Use during pregnancy and lactation
In pregnancy, Nebilet is prescribed only for vital reasons, when the benefit to the mother exceeds the possible risk to the fetus or newborn (due to the possible development of bradycardia, hypotension, hypoglycemia in the fetus and newborn). If Nebilet treatment is necessary, then uteroplacental blood flow and fetal growth should be monitored. Treatment must be interrupted 48-72 hours before delivery. In cases where this is not possible, it is necessary to establish strict monitoring of newborns within 48-72 hours after delivery. Nebivolol is excreted in breast milk. If you need to take the drug Nebilet during lactation, breastfeeding should be stopped.
Dosage and administration
The pills are taken orally, 1 time / day, preferably always at the same time of day, regardless of the meal, with a sufficient amount of liquid. Average daily dose for the treatment of hypertension and coronary heart disease is 2.5-5 mg (1 / 2-1 tab .). Nebilet can be used in monotherapy or in combination with other drugs that reduce blood pressure. In patients with renal insufficiency, as well as in patients over the age of 65, the recommended initial dose is 2.5 mg (1/2 tab.) / Day. If necessary, the daily dose can be increased to a maximum of 10 mg (2 tab. 5 mg per dose). Treatment of chronic heart failure should begin with a slow increase in dose until an individual optimal maintenance dose is reached. Selection of the dose at the beginning of treatment should be carried out according to the following scheme, maintaining at intervals of 1 to 2 weeks and based on the patient's tolerance of this dose: a dose of 1.25 mg nebivolol (1/4 tab. 5 mg) 1 time / day. first increased to 2.5-5 mg (1/2 tab. 5 mg or 1 tab. 5 mg), and then to 10 mg (2 tab. 5 mg) 1 time / day. The maximum daily dose is 10 mg 1 time / day. At the beginning of treatment and at each dose increase, the patient must be under the supervision of a physician for at least 2 hours to ensure that the clinical condition remains with abilnym (especially, blood pressure, heart rate, conduction disturbances, and symptoms of worsening of chronic heart failure).
Side effects
Frequency of side effects: very often (more than 10%), often (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%, including individual reports). From the CNS and peripheral nervous system: often - headache, dizziness, fatigue, weakness, paresthesias; infrequently - depression, nightmares, confusion; very rarely - fainting, hallucinations. From the digestive system: often - nausea, constipation, diarrhea; infrequently - dyspepsia, flatulence, vomiting. From the cardiovascular system: rarely - bradycardia, acute heart failure, AV-blockade, orthostatic hypotension, Raynaud's syndrome. From the skin and subcutaneous tissues: infrequently - skin rash of erythematous nature, itching; very rarely - aggravation of the course of psoriasis; in some cases - angioedema. Other: infrequently - bronchospasm; rarely - dry eyes.
Overdose
Symptoms: marked reduction in blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, AV blockade, bronchospasm, loss of consciousness, cardiogenic shock, coma, cardiac arrest. Treatment: gastric lavage, taking activated charcoal. In the case of a pronounced decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary, in / in the introduction of fluid and vasopressors. For bradycardia, 0.5-2 mg of atropine should be administered intravenously, in the absence of a positive effect, a transvenous or intracardiac pacemaker can be delivered. In case of AV blockade (II-III century), it is recommended intravenous injection of beta-adrenostimulators, if they are ineffective, the question of setting up an artificial pacemaker should be considered. In heart failure, treatment begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to introduce dopamine, dobutamine or vasodilators. When bronchospasm is used in / in stimulators β2-adrenergic receptors. With ventricular estrasystole - lidocaine (antiarrhythmic drugs of class IA should not be administered).
Interaction with other drugs
Pharmacodynamic interaction In the case of simultaneous use of beta-blockers with slow calcium channel blockers (verapamil and diltiazem), the negative effect on myocardial contractility and AV conduction is enhanced. The administration of verapamil against the background of nebivolol use is contraindicated.Nitroglycerin or slow calcium channel blockers can develop severe arterial hypotension (special caution is needed when combined with prazosin). When used simultaneously with nebivolol with class I antiarrhythmic drugs and with amiodarone, negative inotropic effects can be increased and lengthening the time of arousal in the atria can be used. with cardiac glycosides, no increase in the effect on the slowing of AV conduction was detected. Simultaneous use is not bivolol and drugs for general anesthesia may cause the suppression of reflex tachycardia and increase the risk of arterial hypotension. Clinically significant interaction of nebivolol and NSAIDs has not been established. Simultaneous use of nebivolol with tricyclic antidepressants, barbiturates and derivatives of phenothiazine may enhance the use of nephivolol for the treatment of nephivolol and tricyclic antidepressants, barbiturates and fenotiazin derivatives drugs that inhibit serotonin reuptake, or other means MI, biotransforming with the participation of CYP2D6 isoenzyme, increases the concentration of nebivolol in the blood plasma, the metabolism of nebivolol slows down, which may lead to the risk of bradycardia. When used simultaneously with digoxin, nebivolol does not affect the pharmacokinetic parameters of digoxin. blood plasma increases. The simultaneous use of nebivolol and ranitidine does not affect the pharmacokinetic parameters of nebivolol. The simultaneous use of nebivolol with nicardipine increases the concentration of active substances in the blood plasma, but it has no clinical significance. Simultaneous administration of nebivolol and ethanol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol. There is no established clinically significant interaction of nebivolol and warfarin. with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia) can be masked.
special instructions
Cancellation of beta-blockers should be carried out gradually over 10 days (up to 2 weeks in patients with coronary artery disease). Control of blood pressure and heart rate at the beginning of the drug should be daily. In elderly patients, monitoring of renal function is necessary (1 time in 4-5 months ). In case of stenocardia, the dose of the drug should provide the heart rate at rest within 55-60 beats / min, under load - no more than 110 beats / min. Beta-blockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats./min. When deciding on the use of the drug Nebilet in patients with psoriasis Patients using contact lenses should be aware that the use of beta-adrenergic blockers may reduce the production of tear fluid. When performing surgical interventions, the anesthesiologist should be warned that the patient is taking beta-blockers. Nebivolol does not affect the concentration of glucose in the blood plasma in patients with diabetes. However, caution should be exercised in treating these patients, since Nebilet may mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic oral and insulin preparations. Plasma glucose monitoring should be performed once every 4-5 months (in patients with diabetes mellitus). When the thyroid gland is hyperfunctioning, beta-blockers can mask tachycardia. Beta-blockers should be used with caution in patients with chronic obstructive pulmonary disease, because bronchospasm may increase. Beta-blockers may increase sensitivity to allergens and the severity of anaphylactic reactions. Effects on the ability to drive vehicles and control mechanisms. Effect of the preparation. and Nebilet on the ability to drive vehicles and management mechanisms have not been studied specifically. Nebivolol pharmacodynamic studies have shown that Nebilet does not affect psychomotor function. During the period of treatment with Nebilet (if any side effects occur), care should be taken when driving vehicles and when engaging in potentially hazardous activities that require high concentration of attention and quickness of psychomotor reactions.