Nebivolol
Nebivolol: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Nebivolol
ATX code: C07AB12
Active ingredient: nebivolol (nebivolol)
Producer: Berezovsky pharmaceutical plant, CJSC (Russia), VERTEX, CJSC (Russia), IZVARINO PHARMA (Russia), North Star (Russia)
Description and photo update: 2018-25-10
Prices in pharmacies: from 147 rubles.
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Nebivolol is a third generation selective β 1 -adrenergic blocker with vasodilating properties.
Release form and composition
Dosage form of Nebivolol - tablets: from white to almost white, round, flat-cylindrical, with a chamfer and a straight / cross-shaped line on one side (14, 15, 20 or 30 pcs. In blisters made of PVC film and Al foil, either 14, 28 or 60 pieces in polyethylene cans; in a cardboard box 1, 2 or 4 packages of 14 pieces each or 1, 2 or 4 packages of 15 pieces each, or 3 packages of 20 pieces each, or 1-2 packages of 30 pcs., or 1 can).
Composition for 1 tablet:
- active substance: nebivolol - 5 mg (corresponds to the content of nebivolol hydrochloride - 5.45 mg);
- auxiliary components: magnesium stearate, corn starch, lactose monohydrate, microcrystalline cellulose, hyprolose (hydroxypropyl cellulose), croscarmellose sodium, polysorbate 80, colloidal silicon dioxide.
Due to the presence of a large number of manufacturers, other types of packaging may exist and the composition of auxiliary components may change.
Pharmacological properties
Pharmacodynamics
The active component of the drug - nebivolol - has antihypertensive, antianginal and antiarrhythmic efficacy, reduces heart rate (heart rate) and lowers blood pressure (blood pressure) at rest and during exercise; reduces the end diastolic pressure in the left ventricular cavity, normalizing the diastolic function of the heart; reduces the total peripheral vascular resistance, increasing the ejection fraction. Competitively and selectively blocking synaptic and postsynaptic β 1 -adrenergic receptors, makes them inaccessible to catecholamines, modulates the release of endothelial vasodilating factor NO (nitric oxide). Nebivolol is a racemate - an equimolar mixture of two enantiomers: D-nebivolol (SRRR-nebivolol), a competitive and highly selective β blocker1 -adrenergic receptors, and L-nebivolol (RSSS-nebivolol), which has a vasodilating effect by modulating the release of vasodilating factor (NO) from the vascular endothelium.
Hypotensive efficacy is also due to inhibition of the activity of the RAAS (renin-angiotensin-aldosterone system), but there is no direct correlation with changes in the plasma activity of renin.
The antihypertensive effect occurs 2–5 days after the start of treatment, and a stable effect is established after 1–2 months, with prolonged therapy this effect persists.
Due to a decrease in heart rate and a decrease in pre- and afterload under the influence of nebivolol, myocardial oxygen demand decreases, which leads to a decrease in the number and severity of angina attacks and an improvement in exercise tolerance. The antiarrhythmic efficacy of the drug is due to the suppression of the automatism of the heart (including in the pathological zone) and a decrease in the rate of atrioventricular conduction.
Pharmacokinetics
- absorption: after oral administration, both enantiomers of nebivolol are rapidly absorbed; the diet and the qualitative composition of food do not affect their absorption, and therefore the drug can be taken at any convenient time, regardless of the meal. In patients with a fast metabolism, bioavailability is ~ 12% with a first pass metabolism (the effect of the first passage through the liver), in patients with a slow metabolism, the bioavailability of nebivolol is almost complete;
- distribution: the substance enters the systemic circulation, where both enantiomers bind to blood plasma proteins, mainly albumin: D-nebivolol - by 98.1%, L-nebivolol - by 97.9%;
- metabolism: by alicyclic and aromatic hydroxylation, as well as partial N-dealkylation, active metabolites are formed - hydroxy and amino derivatives, which are conjugated with glucuronic acid, after which they are excreted in the form of N- and O-glucuronides. The rate of metabolic processes of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism, depends on the cytochrome isoenzyme CYP2D6;
- excretion: up to 38% of nebivolol taken orally is eliminated by the kidneys (unchanged <0.5%) and 48% is excreted with feces through the intestines. In patients with a fast metabolism, T 1/2 (half-life) of hydroxymetabolites is 24 hours, and of nebivolol enantiomers - 10 hours; with slow metabolism, T 1/2 of hydroxymetabolites is 48 hours, of nebivolol enantiomers - from 30 to 50 hours.
Indications for use
Nebivolol is recommended for the treatment of arterial hypertension, prevention of exertional angina attacks in patients with coronary artery disease (ischemic heart disease), as well as as part of the complex therapy of CHF (chronic heart failure).
Contraindications
Absolute:
- CHF in the stage of decompensation, which requires intravenous administration of drugs with inotropic action;
- acute heart failure;
- severe arterial hypotension, systolic blood pressure <90 mm Hg. Art.;
- SSSU (sick sinus syndrome), including sinoauricular block;
- atrioventricular (AV) block II and III degree without an artificial pacemaker;
- cardiogenic shock;
- severe bradycardia, heart rate <50 beats / min;
- metabolic acidosis;
- pheochromocytoma (except for use in combination with α-blockers);
- history of bronchospasm / bronchial asthma;
- severe liver failure;
- severe renal failure, CC (creatinine clearance) <20 ml / min;
- severe peripheral circulatory disorders (Raynaud's syndrome, intermittent claudication);
- depression;
- muscle weakness, myasthenia gravis;
- lack of lactase, glucose-galactose malabsorption syndrome, lactose intolerance;
- children and adolescents under 18 years of age;
- period of breastfeeding (lactation);
- combined reception with floktaphenin and sultopride;
- simultaneous administration of verapamil intravenously;
- hypersensitivity to nebivolol and / or any other components of the drug.
Nebivolol is recommended to be used with caution in diabetes mellitus, thyroid hyperfunction, COPD (chronic obstructive pulmonary disease), aggravated allergic history, desensitizing therapy, psoriasis, 1st degree AV block, Prinzmetal angina, during pregnancy and in old age (over 65 years old).
Instructions for the use of Nebivolol: method and dosage
Nebivolol is taken by mouth, regardless of the diet, preferably at the same time. The tablets should not be chewed; they must be washed down with a sufficient amount of liquid.
Arterial hypertension and ischemic heart disease
When treating arterial hypertension and ischemic heart disease, an average daily dose of 2.5–5 mg (½ – 1 tablet) 1 time per day is recommended. Achievement of the optimal therapeutic effect occurs after 1-2 weeks of taking the drug, but in some cases it is possible to increase the period to 4 weeks. If necessary, the dose can be increased to a maximum daily dose of 10 mg (2 tablets per dose).
Nebivolol can be used as a monotherapy drug or in combination with other antihypertensive drugs.
The use of Nebivolol for the treatment of arterial hypertension and coronary artery disease in special groups of patients:
- patients with renal insufficiency: initial dose - 2.5 mg (½ tablet) 1 time per day; if necessary, the dose can be increased to a maximum daily dose of 5 mg (1 tablet); the efficacy of nebivolol in severe renal failure (CC <20 ml / min) has not been studied, therefore, the appointment of the drug in such patients is contraindicated;
- patients with hepatic impairment: data on the use of nebivolol are limited, the drug is used with caution; with mild to moderate hepatic impairment, the initial dose is 2.5 mg (½ tablet) once a day; if necessary, the dose can be increased to a maximum daily dose of 5 mg (1 tablet); the efficacy of nebivolol in severe hepatic impairment has not been studied, therefore, the appointment of the drug in such patients is contraindicated;
- elderly patients: patients over 65 years of age take the drug at an initial dose of 2.5 mg (½ tablet) once a day; if necessary, the dose can be increased to a maximum daily dose of 5 mg (1 tablet). Given the limited experience with nebivolol in elderly patients, it must be administered with caution after careful evaluation.
CHF
With a stable course of CHF, treatment should begin with a gradual dose titration until the optimal individual maintenance dose is achieved. During the last 6 weeks, patients should not have attacks of acute heart failure. Treatment must be carried out under close medical supervision.
Patients taking diuretics, cardiac glycosides, ACE (angiotensin converting enzyme) inhibitors, and angiotensin II receptor antagonists should take stable doses of these drugs for at least 2 weeks before starting Nebivolol.
It is necessary to start therapy for CHF with β-adrenergic receptor blockers when the patient is clinically stable for the last 2 weeks. The selection of the dose in the initial period is carried out according to the scheme (maintaining 2-week intervals between dose increases): the initial dose is 1.25 mg per day (¼ tablet), then it can be increased to 2.5 mg per day (½ tablet), then up to 5-10 mg per day (1-2 tablets). The maximum daily dose should not exceed 10 mg (2 tablets). Each stage between increasing doses should last 2 weeks or more, its duration for each patient is individual and depends on the tolerance of the drug.
It is necessary to start treatment and gradually increase the dose of the drug under strict medical supervision, especially during the first two hours. When titrating the dose, blood pressure, heart rate and symptoms of CHF are regularly monitored.
Therapy for stable CHF is usually a lengthy process. It is not recommended to stop taking Nebivolol sharply, since this can lead to a temporary exacerbation of the underlying disease (CHF). If there is a need for a break in treatment, the cancellation is carried out by gradually reducing the dose of the drug by 2 times for 1 week.
The use of Nebivolol for the treatment of CHF in special patient groups:
- patients with renal failure: mild to moderate renal failure (CC> 20 ml per minute) - dose adjustment is not required, the dose is selected individually with a gradual increase to the maximum tolerable. Experience with the use of the drug in severe renal dysfunction (CC <20 ml per minute) is absent, the use of the drug is contraindicated;
- patients with hepatic insufficiency: due to the limited experience of using the drug in case of liver dysfunction, it should be prescribed with caution in mild to moderate hepatic insufficiency, the dose must be selected individually, with a gradual increase to the maximum tolerable, if necessary, it can be increased to the maximum daily - 5 mg (1 tablet). There is no experience with nebivolol in severe hepatic dysfunction, the drug is contraindicated;
- elderly patients: dose adjustment is not required, it should be selected individually, gradually increasing to the maximum tolerated.
Side effects
The frequency of negative side effects according to the WHO (World Health Organization) classification: very often -> 10%, often -> 1% and 0.1% and 0.01% and <0.1%, extremely rarely - <0.01%, including individual cases.
- nervous system: often - dizziness, headache, weakness, increased fatigue, paresthesia; infrequently - nightmares, insomnia, depression, confusion; extremely rare - hallucinations, fainting;
- gastrointestinal tract: often - nausea, diarrhea, constipation; infrequently - flatulence, dyspepsia, vomiting;
- cardiovascular system: often - peripheral edema; infrequently - heart failure, bradycardia, AV blockade, orthostatic hypotension, cardiac arrhythmias, Raynaud's syndrome, cardialgia, aggravation of CHF, marked decrease in blood pressure;
- skin and subcutaneous tissue: infrequently - erythematous rash, pruritus; extremely rare - worsening of the course of psoriasis; in some cases - alopecia, angioedema;
- respiratory system: often - shortness of breath; infrequently - bronchospasm (including in the absence of anamnestic data on obstructive pulmonary disease);
- other reactions: infrequently - photosensitization reactions, visual impairment, impotence, hyperhidrosis; rarely - dryness of the mucous membrane of the eye.
Overdose
Symptoms of nebivolol overdose are nausea / vomiting, hypoglycemia, cyanosis, severe bradycardia, marked decrease in blood pressure, AV blockade, acute heart failure, cardiogenic shock, bronchospasm, loss of consciousness, convulsions, coma, cardiac arrest.
In case of an overdose, the first step is to flush the stomach and take activated charcoal. Further therapy is carried out depending on the symptoms:
- marked decrease in blood pressure: the patient should be laid in a horizontal position and his legs raised above the level of the head; if required, administer intravenous fluids and vasopressors;
- bradycardia: 0.5–2 mg of atropine is injected intravenously; in the absence of a positive effect, it is possible to install an intracardiac or transvenous electrostimulator;
- AV-blockade of II – III degree: β-adrenostimulants are injected intravenously; in the absence of a positive effect, an artificial pacemaker can be installed;
- heart failure: cardiac glycosides and diuretics are administered, in the absence of a positive effect, it is advisable to administer dobutamine, dopamine or vasodilators;
- bronchospasm: β-adrenomimetics are administered intravenously;
- ventricular premature beats: lidocaine is administered (class IA antiarrhythmics cannot be administered);
- convulsions: diazepam is administered intravenously;
- hypoglycemia: intravenous glucose (dextrose) may be needed.
special instructions
Abrupt cessation of β-blockers, including nebivolol, is unacceptable, therapy should be completed gradually, over 10 days (for patients with coronary artery disease - up to 14 days).
Controlling blood pressure and heart rate at the beginning of treatment is required daily.
Elderly patients need to monitor renal function once every 4–5 months.
The selection of the dose of nebivolol in patients with exertional angina should ensure the heart rate at rest - 55–60 beats / min, under load - ≤ 110 beats / min.
Β-blockers can cause bradycardia, and the dose of nebivolol should be reduced when the heart rate is <50–55 bpm.
For patients with psoriasis, the drug is prescribed with caution, after a careful assessment of the ratio of the expected benefits of therapy with the possible risk of exacerbation of the course of psoriasis.
When using contact lenses, it must be borne in mind that due to the use of β-blockers, the production of tear fluid may decrease.
Before surgical interventions, it is required to warn the anesthesiologist about the intake of β-blockers.
Nebivolol has no effect on plasma glucose levels in diabetic patients. But when treating such patients, care should be taken, since a β-blocker can mask some symptoms of hypoglycemia (tachycardia, heart palpitations) caused by oral intake of hypoglycemic agents and the use of insulin. In diabetes mellitus, the concentration of glucose in the blood plasma should be monitored at least once every 4–5 months.
In patients with hyperfunction of the thyroid gland, β-blockers are able to mask tachycardia.
Β-blockers are recommended to be used with caution in patients with COPD (chronic obstructive pulmonary disease), since they can increase bronchospasm.
If you are prone to allergies, it is important to consider that β-blockers can increase sensitivity to allergens, as well as the severity of anaphylaxis.
In smoking patients, the effectiveness of β-blockers is lower than in nonsmokers.
Influence on the ability to drive vehicles and complex mechanisms
During treatment with Nebivolol (due to possible adverse reactions), care should be taken when driving vehicles and complex mechanisms, as well as performing potentially dangerous types of work that require increased concentration of attention and rapid psychomotor reactions.
Application during pregnancy and lactation
According to the instructions, Nebivolol during pregnancy is prescribed only according to strict indications, provided that the benefits for the mother exceed the risk for the fetus, since drug therapy can contribute to delayed growth and development of the fetus, premature labor, the development of a decrease in blood pressure in a newborn, bradycardia, hypoglycemia, paralysis respiration, as well as intrauterine fetal death. Taking tablets should be discontinued 48–72 hours before the onset of labor, and if this is not possible, monitor uteroplacental blood flow, as well as strict observation of the newborn during the first 3 days after birth.
In animal studies, it was found that nebivolol passes into breast milk. If it is necessary to take the drug during lactation, breastfeeding must be interrupted.
Pediatric use
The use of Nebivolol in children and adolescents under the age of 18 is contraindicated due to insufficient data on safety and efficacy.
With impaired renal function
Caution should be exercised in the treatment of arterial hypertension and ischemic heart disease in patients with impaired renal function of any severity, as well as in the treatment of CHF with mild to moderate renal failure.
Due to the lack of experience in the use of nebivolol for the treatment of CHF in severe renal dysfunction with CC <20 ml per minute, its use is not recommended.
For violations of liver function
Due to the limited experience of using Nebivolol for mild to moderate liver dysfunction, it should be prescribed with caution, the dose should be selected individually, with a gradual increase to the maximum tolerable. There is no experience with nebivolol therapy in severe hepatic impairment; the drug is contraindicated.
Use in the elderly
Caution should be exercised in the treatment of hypertension and coronary artery disease in elderly patients.
There is no need for dose adjustment in the treatment of CHF in elderly patients; it should be selected individually, gradually increasing to the maximum tolerable.
Drug interactions
Pharmacodynamic interaction:
- verapamil and diltiazem - BMCC (slow calcium channel blockers): β-blockers increase their negative effect on myocardial contractility and AV conduction; intravenous verapamil is contraindicated when taking nebivolol;
- antihypertensive drugs, nitroglycerin: the development of severe arterial hypotension is possible (special care should be taken when combined with prazosin);
- BMCC dihydropyridine series (amlodipine, nitrendipine, nifedipine, lacidipine, nicardipine, nimodipine, felodipine): the likelihood of arterial hypotension may increase; in patients with CHF, the possibility of a further decrease in the contractility of the heart muscle cannot be excluded;
- centrally acting antihypertensive drugs (methyldopa, clonidine, moxonidine, guanfacine, rilmenidine): heart failure may worsen due to a decrease in sympathetic tone (decrease in heart rate and decrease in cardiac output, symptoms of vasodilation); with abrupt withdrawal of these drugs, especially before the withdrawal of nebivolol, the development of rebound arterial hypertension is possible;
- amiodarone, class I antiarrhythmics (hydroquinidine, quinidine, propafenone, flecainide, cybenzoline, lidocaine, disopyramide, mexiletine): it is possible to increase their negative inotropic effect and lengthen the time of excitation through the atria;
- cardiac glycosides: suppression of atrioventricular conduction is possible;
- means for general anesthesia: suppression of reflex tachycardia and an increase in the risk of developing arterial hypotension is likely;
- NSAIDs (non-steroidal anti-inflammatory drugs): no clinically significant drug interaction with nebivolol has been established;
- acetylsalicylic acid: can be used with nebivolol as an antiplatelet drug;
- tricyclic antidepressants, barbiturates and phenothiazine derivatives, anxiolytics, hypnotics, ethanol: may enhance the hypotensive effect of nebivolol;
- insulin and oral hypoglycemic agents: nebivolol can mask symptoms of hypoglycemia (palpitations, tachycardia);
- floctaphenin: nebivolol may inhibit the compensatory reactions of the cardiovascular system associated with arterial hypotension or shock, which floktaphenin can cause (concomitant use is contraindicated);
- baclofen, amifostine: possible increased arterial hypotension;
- sultopride: the risk of pirouette-type ventricular arrhythmias increases (simultaneous administration with nebivolol is contraindicated).
Pharmacokinetic interaction:
- serotonin reuptake inhibitors, other drugs that biotransform with the participation of the isoenzyme CYP2D6: increase the plasma concentration of nebivolol, slow down its metabolism, as a result of which bradycardia may develop;
- digoxin: nebivolol has no effect on its pharmacokinetic parameters;
- cimetidine: increases the plasma concentration of nebivolol (no data on the effect on pharmacological efficacy);
- rifampicin: increases the metabolism of nebivolol;
- ranitidine: does not affect the pharmacokinetics of nebivolol;
- nicardipine: plasma concentrations of active substances increase slightly, which does not have a clinically significant effect;
- ethanol, furosemide, hydrochlorothiazide: do not alter the pharmacokinetic parameters of nebivolol;
- warfarin: no clinically significant interaction with nebivolol has been established;
- sympathomimetic agents: inhibit the pharmacological activity of nebivolol.
Analogs
Analogues of Nebivolol are: Binelol, Bivotenz, Nebivolol Sandoz, Nebivolol Canon, Nebivolol Stada, Nebivolol-Nanolek, Nebivolol-SZ, Nebivolol-Teva, Nebivolol-Chaykapharma, Nebivator, Nebikor Adipharm, Nebiletan, NevotenzDevotenz dr.
Terms and conditions of storage
Store at temperatures up to 25 ° C in a dark place. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Nebivolol
According to reviews, Nebivolol is a fairly effective drug that eliminates pressure problems, and also normalizes the pulse, but at the same time it can cause many and often manifested side reactions.
The price of Nebivolol in pharmacies
The price of Nebivolol depends on the manufacturer and the number of tablets in the package and can be approximately: for 14 tablets - 165–214 rubles, 28 tablets - 190–280 rubles.
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Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
