Nebitred

Non -bitrand is an elective that blocks the activity of β-adrenergic receptors.

Indications Nebitrenda

It is used for the treatment of primary hypertension, and also as an additional remedy with standard drugs for CHF in the elderly (over 70 years old). 

Release form

The release is made in tablets packed in 7 pieces inside the blister plate (the pack contains 4 such plates). Also in the blister plate can contain 10 tablets - these plates in the box 3 pieces.

Pharmacodynamics

Nebivolol is a racemate substance containing 2 enantiomers: nebivolol type SRRR (D-nebivolol), and nebivolol type RSSS (L-nebivolol). It combines such therapeutic properties: the D-enantiomer has a selective competitive blocking of the activity of β1-adrenergic receptors, and the L-enantiomer has a mild vasodilating effect, provided by metabolic interaction with the L-arginine / NO substance.

After a 1-time and repeated use of drugs, the HR index decreases with loads and in a calm state (in people with normal blood pressure and in individuals with elevated values).

The hypotensive effect of the drug continues to persist with prolonged therapy. Medicinal portions do not cause the development of α-adrenergic antagonism. With a short and prolonged therapy in persons with elevated BP indices, systemic vascular resistance is weakened. Although the heart rate decreases, the attenuation of cardiac output in a calm state or load is limited, due to an increase in the impact volume.

What is the clinical significance of hemodynamic differences in comparison with the indices when using other drugs that block β-adrenergic receptors has not been studied enough so far. In people with elevated blood pressure, the drug enhances the vascular response to the effect of acetylcholine, which occurs through nitrogen monoxide. In people with problems in the work of the endothelium, this reaction is weakened.

When using Non-Tribend in the form of an additional substance in the standard treatment of CHF with a weakening fraction of left ventricular ejection (or without it), the period of hospitalization or death due to SSS disease is significantly prolonged.

People who took the medicine had a decrease in the incidence of sudden-onset deaths.

Pharmacokinetics

When administered orally, the absorption of the enantiomers of nebivolol occurs at a high rate. The intake of food has no effect on absorption, which makes it possible to apply the drug without being tied to food.

Exchange processes of the medicine occur inside the liver; at the same time hydroxymetabolites possessing medicinal activity are formed. Values of bioavailability of ingested nebivolol on average are 12% in people with a high rate of metabolic processes and almost a full rate in people with low rates. Given the difference in the speed of these processes, it is necessary to select a portion of the drug taking into account the individual characteristics of the patient (people with a lower metabolic rate should be assigned lower dosages).

In people with a high metabolic rate, the half-life of enantiomers is on average 10 hours, and in people with a slow rate this rate is higher (3-5 times). Plasma values, which are within the range of 1-30 mg of the substance, are proportional to the size of the dose.

After 7 days from the moment of taking drugs, the substance is excreted (with urine - 38%, and with faeces - 48%). In the unchanged state with urine nebivolol is excreted only less than 0.5% of the portion.

Equilibrium plasma values of the active substance in most patients (with a high metabolic rate) are noted after 24 hours, and indicators of hydroxy metabolites - after a few days.

Enantiomers are synthesized with proteins (mainly with albumin). In this case, SRRR-nebivolol is synthesized by 98.1%, and RSSS-nebivolol - by 97.9%.

Dosing and administration

Use the drug orally, taking the pill with plain water. Drug reception is not tied to eating.

Primary hypertension.

It is required to take 1 tablet of medicine (5 mg of substance) per day. It is recommended to do this at the same time of day.

The optimal antihypertensive effect develops after 1-2 weeks of therapy, but in individual cases the result should be expected during the first month.

The drug can be used as a monotherapy, and in addition in combination with other antihypertensive medications. It should be borne in mind that additional antihypertensive effect was noted only when combined with hydrochlorothiazide (portion 12.5-25 mg).

Patients with CHF.

Therapy for CHF is required to start with a slow dosage titration - until the optimum support portion for the patient is obtained. Such treatment is provided for people with CHF without episodes of decompensation in acute form during the last 1.5 months. The attending doctor should have experience of CHF therapy.

People who use other drugs to improve the work of CCC (dioxin with diuretics, ACE inhibitors, as well as antagonists of angiotensin 2 endings), it is necessary to choose a dose of this drug for the last 14 days before using Non-Grad.

The initial dosing titration is carried out according to the scheme below, observing intervals of 1-2 weeks, and also taking into account the tolerance of this dosage by the patient: with a dose of 1.25 mg of LS, 1 day per day, it is allowed to increase to 5 mg of the drug per day . Further, the dosage is increased to 10 mg with 1-time administration per day. The indicated dosage is the maximum allowable for administration per day.

At the initial stage of therapy, as well as every increase in the dose, the patient should be at least 2 hours under the supervision of an experienced doctor to confirm that his clinical condition remains stable (in particular, this is important for values of blood pressure and heart rate, myocardial conductivity disorders, and together with this in potentiating the signs of heart failure).

If required, the dosage already received can be gradually phased out or returned to it again.

When potentiating the signs of heart failure or hypersensitivity to drugs at the stage of titration, the portion of nebivolol should first be reduced or, if necessary, immediately abolished its administration (if there are manifestations of heart failure accompanied by acute pulmonary edema, the blood pressure decreases sharply, a symptomatic bradycardia develops, cardiogenic shock or AV blockade). Often, for the treatment of CHF medication should be used for a long time.

Therapy with the use of medication can not be stopped suddenly, because as a result, signs of a heart failure may be potentiated. If need is necessary to abolish the use of drugs, reducing the portion in stages - every week reducing by half.

People with kidney failure.

For a day you need to take 2.5 mg of the substance. If necessary, the dosage for the day can be increased to 5 mg.

Elderly people (> 65 years old).

First you need to use 2.5 mg of medication per day, and then, if necessary, increase the dose to 5 mg. Also, in connection with the fact that experience of using drugs is inadequate for people over 75 years of age, treatment with this age group is necessary with very great care and only under medical supervision.

[2]

Use Nebitrenda during pregnancy

The therapeutic effect of nebivolol can provoke a negative effect on the course of pregnancy, as well as on the fetus and the newborn. Because of this, in this period it is used only in cases where the benefits for women are more likely than the appearance of complications in the fetus. 

Contraindications

The main contraindications:

• the presence of intolerance with respect to the active element of the drug or other components;
• insufficiency of hepatic activity or a disorder in the functioning of the liver;
• untreated pheochromocytoma;
• heart failure in the acute stage, as well as cardiogenic shock or episodes with the development of decompensation, in which it is necessary to introduce active elements that have a positive isotropic effect;
• SSSU (this includes also a blockade of the sinouauric nature) and AV blockade of the 2-3rd degree (no pacemaker);
• bronchial spasms or asthma, available in history;
• acidosis, which has a metabolic character;
• bradycardia (before the start of therapy, heart rate is <60 beats / minute);
• reduced blood pressure (systolic blood pressure is <90 mm Hg), as well as disorders of peripheral blood flow in a severe degree.

Side effects Nebitrenda

Side-effects that occur in people with primary hypertension:

• mental disorders: sometimes depression develops or nightmares appear;
• disorders of the NA function: often there are paresthesias, dizziness and headaches. Single fainting occurs;
• problems with visual organs: sometimes visual disturbances are observed;
• lesions affecting the respiratory system: dyspnea often appears. Sometimes spasms of bronchi arise;
• disorders of digestive activity: often there is nausea, constipation or diarrhea. Sometimes, vomiting, dyspepsia or bloating develops;
• symptoms on the epidermis and subcutaneous tissues: sometimes there are eruptions of the erythematous nature or itching. There is an exacerbation of psoriasis;
• disorders in the work of the CCC: sometimes develop heart failure, aetiology, lowering the level of AD, inhibition of AV-conductivity or AV-blockade, as well as intermittent claudication;
• systemic manifestations: often there are swelling and increased fatigue;
• immune lesions: may develop intolerance or edema Quincke;
• violations of the function of the reproductive organs and mammary glands: sometimes there is impotence.

There are also data on the development of disorders caused by individual β-blockers: psychoses with hallucinations, cyanosis in the limbs, confusion, Raynaud's disease, toxic eye mucosa (similar to pratolol) and dry eye mucosa.

Disorders occurring in individuals with CHF.

Most often with the use of Nebitendra, there was an appearance of dizziness or the development of bradycardia.

There are also negative symptoms (which may be associated with the use of drugs), which are considered to be the most common during therapy during CHF:

• potentiation of signs of heart failure;
• orthostatic collapse;
• AV blockade, having the 1st degree;
• swelling in the legs;
• an allergic reaction to the drug.

[1]

Overdose

In the case of intoxication with β-adrenoblockers, there is a spasm of bronchi, a bradycardia, an incomplete heart failure and a decrease in the level of blood pressure.

To treat the disorder, you must first rinse the stomach, and then appoint the recipient to take laxatives with activated charcoal. In addition, it is required to monitor blood sugar values. If necessary, intensive therapy is performed at the hospital: with the development of enhanced vagotonia or bradycardia, atropine is administered, and in the shock state or reduced values of blood pressure, catecholamines with plasma substitutes are used.

The development of the β-blocking effect can be stopped by injecting isoprenaline hydrochloride at low speed (starting at 5 μg / minute) or dobutamine (starting at a dose of 2.5 μg / minute) until the desired result is obtained.

If there is no result after using the above measures, glucagon should be applied at a dosage of 50-100 μg / kg. After this, if necessary, the injection is repeated for 60 minutes, and also perform the infusion of the substance in a dose of 70 μg / kg / h.

In extreme situations, artificial pulmonary ventilation is performed, and a pacemaker is connected.

Interactions with other drugs

It is forbidden to combine Nebitrend with sultopride, as well as floktaphenin.

In addition, among the forbidden combinations of the drug with anti-arrhythmic drugs of the first series (among them quinidine, lidocaine and propafenone with flecainide, and in addition, hydroquinidine, cibenzoline and mexiletine with disopyramide), drugs blocking the Ca channels (in this list verapamil with diltiazem) , as well as antihypertensive medications with a central effect (among them clonidine, rilmenidine, moxonidine with methyldopa and guanfacine).

Simultaneous use of the drug and furosemide, hydrochlorothiazide or alcoholic beverages does not affect its pharmacokinetic characteristics.

[3], [4]

Storage conditions

Non-grant is required to be kept in a place that is closed from small children. The room temperature is standard.

Shelf life

Non -bitrand is allowed to be used within 36 months from the date of release of the medicinal product.

Application for children

Tests regarding the use of Non-Graduate in pediatrics were not carried out, because of which this age category is not assigned.

Analogues

Analogues of the medication are Nebival, Nebitens, Nebilot with Nebivolol Orion, Nebikard with Nebivolol Sandoz, and also Nebilong and Nebivolol Teva.