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Active ingredients
Nebivolol
Release form
Pills
Composition
1 tab.: Nebivolol (in the form of hydrochloride) 5 mg. Adjuvants: lactose monohydrate - 85.96 mg, crospovidone (type A) - 6.89 mg, poloxamer 188 - 6.9 mg, povidone K-30 - 3.5 mg, microcrystalline cellulose - 119 mg , magnesium stearate - 2.3 mg.
Pharmacological effect
Cardioselective lipophilic beta1-adrenergic blocker of the third generation with vasodilating properties. It has a hypotensive, antianginal and antiarrhythmic effect. Reduces increased blood pressure at rest, with physical exertion and stress. Competitively and selectively blocks synaptic and postsynaptic β1-adrenoreceptors, making them inaccessible to catecholamines, modulates the release of the endothelial vasodilating factor nitric oxide (NO). Nebivolol is a racemate consisting of two enantiomers: SRRR-nebivol-β-α-β-α-α-α-α-β-β-racemicate, a racemate that consists of two enantiomers; (L-nebivolol), combining two pharmacological actions: - D-nebivolol is a competitive and highly selective blocker of β1-adrenoreceptors (affinity for β1-adrenergic receptors is 293 times higher than for β2-adrenoretic ; - L-nebivolol has a mild vasodilating effect due to modulation of the release of the relaxing factor (NO) from the vascular endothelium. The hypotensive effect develops on the 2nd-5th day of treatment, a stable effect is observed after 1 month. The antihypertensive effect persists with long-term treatment. The hypotensive effect is also due to a decrease in the activity of the renin-angiotensin system (it does not directly correlate with changes in the activity of renin in blood plasma). The use of nebivolol improves systemic and intracardiac hemodynamics. Nebivolol decreases heart rate and blood pressure at rest and during physical exertion, reduces the end diastolic pressure of the left ventricle, decreases OPSS, improves heart diastolic function (decreases filling pressure), increases the ejection fraction. Decreasing myocardial oxygen demand (reduced heart rate, reduced preload and afterload) , reduces the number and severity of angina attacks and increases exercise tolerance. The antiarrhythmic effect is due to the suppression of the pathological automatism of the heart (including in the pathological chaga) and AV-conduction slowing.
Pharmacokinetics
AbsorptionAfter ingestion, nebivolol is rapidly absorbed from the gastrointestinal tract. Meal does not affect absorption, so nebivolol can be taken regardless of the meal. Bioavailability averages 12% in patients with a fast metabolism and is almost complete in patients with a slower metabolism. The effectiveness of nebivolol does not depend on the rate of metabolism. The distribution of plasma clearance in most patients (with rapid metabolism) is achieved within 24 hours, and for hydroxymetabolites - in a few days. Plasma concentrations of 1-30 mcg / l are proportional to the dose. Binding to plasma proteins (mainly albumin) is 98.1% for D-nebivolol and 97.9% for L-nebivolol. Metabolism Nebivolol is extensively metabolized, partly with the formation of active hydroxymetabolites. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the CYP2D6 isoenzyme. Excretion Within a week after administration of 38% (the amount of unchanged active substance is less than 0.5%) the dose is eliminated by the kidneys and 48% through the intestines. In patients with fast metabolism, T1 / 2 enantiomers of nebivolol from blood plasma average 10 hours. In patients with slow metabolism, these values increase 3-5 times. In patients with fast metabolism, the values of T1 / 2 hydroxymetabolites of both enantiomers from blood plasma are on average, 24 hours, in patients with slow metabolism, these values increase by about 2 times. The age and sex of patients do not affect the pharmacokinetics of nebivolol.
Indications
- arterial hypertension; - ischemic heart disease: prevention of strokes of exertional angina - chronic heart failure (as part of combination therapy).
Contraindications
- severe liver dysfunction; - acute heart failure; - chronic heart failure in the decompensation stage (requiring intravenous administration of drugs with an inotropic effect); - cardiogenic shock; - sinus node weakness syndrome, including sinoauricular blockade; - AV blockade II and III degree (without artificial pacemaker); - bronchospasm and bronchial asthma; - untreated pheochromocytoma; - depression; - metabolic acidosis; - severe bradycardia (heart rate less than 50 beats / min); - severe arterial hypotension (systolic hell blood pressure less than 90 mm Hg); - severe obliterating diseases of peripheral vessels (intermittent claudication, Raynaud's syndrome); - myasthenia; - age up to 18 years; - lactose intolerance,lactase deficiency or glucose / galactose malabsorption syndrome; hypersensitivity to nebivolol or one of the components of the drug. The drug should be prescribed with caution in renal failure, diabetes, hyperthyroidism, history of allergies, psoriasis, AV block I degree, angina pectoris Prinzmetala, chronic obstructive pulmonary disease, in patients over 65 years old.
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
In pregnancy, the drug is prescribed only under strict indications, when the potential benefit to the mother exceeds the risk to the fetus (due to the possible development of bradycardia, hypotension, hypoglycemia and respiratory paralysis in the newborn). Treatment must be interrupted 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict monitoring of the newborn within 48-72 hours after delivery. Studies on animals have shown that nebivolol is excreted in breast milk. If the use of the drug during lactation is necessary, then breastfeeding should be stopped.
Dosage and administration
Binelol should be taken orally at the same time of the day, regardless of the meal, without chewing and drinking plenty of fluids. The average daily dose for the treatment of hypertension and coronary heart disease is 2.5-5 mg 1 time / day. It is possible to use the drug in monotherapy or as part of combination therapy. In patients with renal insufficiency, as well as in patients over the age of 65, the initial dose is 2.5 mg / day. If necessary, the daily dose can be increased to 10 mg (in one step). Treatment chronic heart failure should begin with a gradual increase in dose to achieve an individual optimal maintenance dose. Selection of a dose at the beginning of treatment should be carried out according to the following scheme, maintaining weekly intervals and yvayas on patient tolerability of that dose: Dose 1.25 mg 1 time / day may be increased to 2.5-5 mg at first, and then - 1 to 10 mg once / day.
Side effects
From the central and peripheral nervous system: headache, dizziness, fatigue, weakness,paresthesias (from 1% to 10%); very rarely - depression, decreased ability to concentrate, drowsiness, insomnia, nightmares, hallucinations, psychosis, convulsions. On the part of the digestive system: nausea, constipation, flatulence, diarrhea, dry mouth (> 1%). vascular system: bradycardia, acute heart failure, AV-blockade, orthostatic hypotension, exacerbation of intermittent claudication, shortness of breath; very rarely - cardiac arrhythmias, Raynaud's syndrome, peripheral edema, cardialgia. Allergic reactions: pruritus, erythematous rash. psoriasis, visual disturbances, dry eyes.
Overdose
Symptoms: decreased blood pressure, nausea, vomiting, cyanosis, sinus bradycardia, AV blockade, bronchospasm, cardiogenic shock, loss of consciousness, 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, with / in the introduction of fluid and vasopressors; as a follow-up, the administration of 1-10 mg of glucagon is possible. In case of bradycardia, 0.5-2 mg of atropine is injected intravenously, in the absence of a positive effect, a transvenous or intracardiac pacemaker is possible. In case of AV blockade (II and III degrees), it is recommended IV injection of beta-adrenomimetics, if they are ineffective, consideration should be given to setting up an artificial pacemaker. 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 prescribed in / in beta2-adrenomimetics. For ventricular premature beats, lidocaine (antiarrhythmic agents of class I A should not be administered). When convulsions - in / in diazepam.
Interaction with other drugs
With simultaneous use of beta-blockers with slow calcium channel blockers (BMCC) (verapamil and diltiazem), the negative effect on myocardial contractility and AV conduction is enhanced. It is contraindicated in / in the introduction of verapamil while taking nebivolol. In combination with antihypertensives,pronounced arterial hypotension may develop (nitroglycerin or BCCA) (special caution is necessary when combined with prazosin). When used simultaneously with class I antiarrhythmic agents and with amiodarone, it is possible to increase the negative inotropic effect and lengthen the time of arousal in the atria. revealed an increase in the effect on the slowing of AV conduction. Simultaneous use of nebivolol and drugs for general anesthesia may binding inhibition of the reflex tachycardia and increase the risk of arterial gipotenzii.Klinicheski significant interaction nebivolol and NSAIDs have not been established. Acetylsalicylic acid as an antiplatelet agent can be used simultaneously with nebivolol. Simultaneous use of tricyclic antidepressants, barbiturates and phenothiazine derivatives may enhance the hypotensive effect of nebivolol. nebivolol slows down. When used simultaneously, nebivolol is not about He did not influence the pharmacokinetic parameters of digoxin. When used simultaneously with cimetidine, plasma concentration of nebivolol increases (there are no data on the effect on the pharmacological effects of the drug). Simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol. blood plasma increased slightly, but it has no clinical significance. Simultaneous administration of ethanol, furosemide hydrochlorothiazide or no effect on the pharmacokinetics nebivolola.Ne established clinically significant interaction nebivolol and varfarina.Pri simultaneous application of sympathomimetic agents inhibit the activity of nebivolol.
special instructions
Cancellation of beta-blockers should be carried out gradually over 10 days (up to 2 weeks in patients with coronary artery disease). The 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, with a load of no more than 110 beats / min. Beta-blockers can cause bradycardia, therefore the dose should be reduced,if the heart rate is less than 50-55 beats / min. When deciding on the administration of Binelol to patients with psoriasis, you should carefully relate the perceived benefits of using the drug and the possible risk of exacerbation of psoriasis. Patients using contact lenses should consider adrenergic blockers may reduce the production of tears. When performing surgical interventions, an anesthesiologist should be warned that the patient is taking beta-adrenergic blockers. Nebivolol does not affect the level of glucose patients with diabetes. However, caution should be exercised in treating these patients, since Binelol may mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic agents. In diabetic patients, plasma glucose monitoring should be performed 1 time in 4-5 months. Beta-blockers should be used with caution in patients with chronic obstructive pulmonary disease, as bronchospasm may increase. Beta-blockers can increase sensitivity to allergies. us and the severity of anaphylactic reactions. The effectiveness of beta-blockers in smoking patients is lower than in non-smoking patients. The impact on the ability to drive vehicles and control mechanisms. Research has shown that nebivolol does not affect the speed of psychomotor reactions. Pilots of pilots with a mild degree of arterial hypertension (approved for flight work) are prescribed the drug in an initial dose of 2.5 mg. In the future (no earlier than 2 weeks) with good tolerability of treatment and insufficient control of blood pressure, it is possible to increase the dose by 2.5 mg. The recommended dose is 5 mg / day. Some patients may experience side effects, most often dizziness, due to low blood pressure. If such effects occur, the patient should not drive vehicles or engage in potentially hazardous activities that require special attention and speed of psychomotor reactions. These effects occur most often immediately after the start of treatment or with increasing doses.