Nebitrend

Nebitrend is a selective agent that blocks the activity of β-adrenergic receptors.

Indications Nebitrenda

It is used to treat primary hypertension, and also as an additional agent together 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 a blister plate (there are 4 such plates in a pack). Also, a blister plate can contain 10 tablets - there are 3 such plates in a box.

Pharmacodynamics

Nebivolol is a racemate substance that includes 2 enantiomers: nebivolol of the SRRR type (D-nebivolol) and nebivolol of the RSSS type (L-nebivolol). It combines the following therapeutic properties: the D-enantiomer has a selective competitive blockade of β1-adrenergic receptor activity, and the L-enantiomer has a mild vasodilatory effect, provided by metabolic interaction with the substance L-arginine/NO.

After a single and repeated use of the drug, the heart rate decreases during exercise and at rest (in people with normal blood pressure and in people with elevated values).

The hypotensive effect of the drug continues to be maintained during long-term therapy. Medicinal doses do not cause the development of α-adrenergic antagonism. With short-term and long-term therapy in individuals with elevated blood pressure, systemic vascular resistance is weakened. Although the heart rate values are reduced, the weakening of cardiac output at rest or under load is limited due to an increase in stroke volume.

The clinical significance of hemodynamic differences compared to other β-adrenergic blocking drugs has not yet been adequately studied. In people with elevated blood pressure, the drug enhances the vascular response to acetylcholine, which occurs via nitrogen monoxide. In people with endothelial dysfunction, this response is weakened.

When Nebitrend is used as an additional substance in the standard treatment of CHF with or without a weakened left ventricular ejection fraction, the time to hospitalization or death due to cardiovascular disease is significantly prolonged.

A reduction in the incidence of sudden death was observed in people taking the drug.

Pharmacokinetics

When taken orally, the absorption of nebivolol enantiomers occurs at a high rate. Food intake does not affect absorption, which allows the drug to be used without reference to food intake.

The metabolic processes of the drug occur in the liver; in this case, hydroxymetabolites with medicinal activity are formed. The bioavailability values of orally administered nebivolol average 12% in people with a high metabolic rate and almost the full value in people with a low rate. Given the difference in the speed of these processes, the dose of the drug must be selected taking into account the individual characteristics of the patient (people with a low metabolic rate should be prescribed lower dosages).

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

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

In most patients (with a high metabolic rate), equilibrium plasma values of the active substance are observed after 24 hours, and hydroxymetabolite values after several 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

The drug should be taken orally, with a tablet washed down with plain water. Taking the drug is not tied to food intake.

Primary hypertension.

It is necessary to take 1 tablet of the medicine (5 mg of the 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 some cases the result must be expected within 1 month.

The drug can be used as monotherapy, and also in combination with other antihypertensive drugs. It should be taken into account that additional hypotensive effect was noted only when the drug was combined with hydrochlorothiazide (12.5-25 mg dose).

Patients with CHF.

Therapy for CHF should be started with slow titration until the optimal maintenance dose is obtained for the patient. This treatment is intended for people with CHF without episodes of acute decompensation over the past 1.5 months. The attending physician should have experience in CHF therapy.

People using other medications to improve the functioning of the cardiovascular system (dioxin with diuretics, ACE inhibitors, as well as angiotensin II receptor antagonists) need to adjust the dose of this drug during the last 14 days before starting to use Nebitrend.

The initial dosage titration is performed according to the scheme below, observing intervals of 1-2 weeks, and also taking into account the patient's tolerance of this dosage: with a dose of 1.25 mg of the drug once a day, it is allowed to increase it to 5 mg of the drug per day. Then the dosage is increased to 10 mg with a single dose per day. The last dosage indicated is the maximum permissible dose per day.

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

If necessary, the dosage already received can be gradually reduced or returned to again.

If signs of heart failure or hypersensitivity to the drug increase during titration, the dose of nebivolol should first be reduced or, if necessary, its administration should be stopped immediately (if signs of heart failure occur, accompanied by acute pulmonary edema, blood pressure readings decrease sharply, symptomatic bradycardia, cardiogenic shock or AV block develop). Often, the drug must be used for a long time to treat CHF.

Therapy using the drug should not be stopped suddenly, because it may result in potentiation of signs of heart failure. If necessary, it is necessary to stop using the drug, reducing the dose gradually - reducing it by half every week.

People with renal insufficiency.

It is required to take 2.5 mg of the substance per day. If necessary, the daily dosage can be increased to 5 mg.

Elderly people (> 65 years).

At first, you need to use 2.5 mg of the drug per day, and then, if necessary, increase the dose to 5 mg. Also, due to the fact that for people over 75 years of age, the experience of using the drug is insufficient, therapy in this age group must be carried out with great caution and only under medical supervision.

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Use Nebitrenda during pregnancy

The therapeutic effect of nebivolol can provoke a negative impact on the course of pregnancy, as well as on the fetus and newborn. For this reason, in this period it is used only in cases where the benefit to the woman is more likely than the occurrence of complications in the fetus.

Contraindications

Main contraindications:

• the presence of intolerance to the active element of the drug or other components;
• liver failure or liver dysfunction;
• untreated pheochromocytoma;
• acute cardiac failure, as well as cardiogenic shock or episodes with the development of decompensation, in which it is necessary to administer active elements that have a positive isotropic effect;
• SSSU (this also includes sinoauricular block) and 2nd-3rd degree AV block (pacemaker is absent);
• history of bronchospasms or bronchial asthma;
• acidosis of metabolic nature;
• bradycardia (before the start of therapy, heart rate values are <60 beats/minute);
• reduced blood pressure (systolic blood pressure level is <90 mm Hg), as well as severe disorders of peripheral blood flow processes.

Side effects Nebitrenda

Side effects that occur in people with primary hypertension include:

• mental disorders: sometimes depression develops or nightmares appear;
• disorders of the nervous system function: paresthesia, dizziness and headaches often occur. Fainting occurs sporadically;
• problems with the visual organs: sometimes visual disturbances are observed;
• lesions affecting the respiratory system: dyspnea often occurs. Sometimes bronchial spasms occur;
• digestive disorders: nausea, constipation or diarrhea often occur. Sometimes vomiting, dyspepsia or bloating develop;
• symptoms on the epidermis and subcutaneous tissues: sometimes erythematous rashes or itching occur. Occasionally, psoriasis worsens;
• disorders in the functioning of the cardiovascular system: sometimes heart failure, bradycardia, decreased blood pressure, inhibition of AV conduction or AV block, as well as intermittent claudication develop;
• systemic manifestations: swelling and increased fatigue are often observed;
• immune disorders: possible development of intolerance or Quincke's edema;
• dysfunction of the reproductive organs and mammary glands: sometimes impotence occurs.

There are also data on the development of disorders provoked by individual β-blockers: psychosis with hallucinations, cyanosis in the extremities, a feeling of confusion, Raynaud's disease, toxic damage to the ocular mucosa (similar to the effects of practolol) and dry eye mucosa.

Disorders occurring in individuals with CHF.

The most common side effects observed with Nebitrend include dizziness or bradycardia.

Also noted are the following negative symptoms (which may be associated with the use of drugs), which are considered to be the most frequently occurring during therapy during CHF:

• potentiation of signs of heart failure;
• orthostatic collapse;
• AV block of the 1st degree;
• swelling in the legs;
• allergic reaction to a drug.

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Overdose

In case of intoxication with β-blockers, bronchospasm, bradycardia, acute cardiac failure and a decrease in blood pressure occur.

To treat the disorder, you must first wash out the stomach, and then prescribe the victim laxatives with activated carbon. In addition, it is necessary to monitor blood sugar levels. If necessary, intensive therapy is carried out in the hospital: if increased vagotonia or bradycardia develops, atropine is administered, and in case of shock or low blood pressure, catecholamines with plasma substitutes are used.

The development of the β-blocking effect can be stopped by administering isoprenaline hydrochloride at a low rate (starting with a dose of 5 mcg/minute) or dobutamine (starting with a dose of 2.5 mcg/minute) until the desired result is achieved.

If there is no result after using the above measures, glucagon should be used at a dosage of 50-100 mcg/kg. After that, if necessary, the injection is repeated for 60 minutes, and an infusion of the substance is performed in a portion of 70 mcg/kg/hour.

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

Interactions with other drugs

It is prohibited to combine Nebitrend with sultopride and floctafenine.

In addition, combinations of the drug with first-line antiarrhythmic drugs (including quinidine, lidocaine, and propafenone with flecainide, as well as hydroquinidine, cibenzoline, and mexiletine with disopyramide), drugs that block Ca channels (including verapamil with diltiazem), and antihypertensive drugs with a central effect (including clonidine, rilmenidine, moxonidine with methyldopa, and guanfacine) are also prohibited.

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

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Storage conditions

Nebitrend should be kept in a place closed to small children. The room temperature is standard.

Shelf life

Nebitrend is allowed to be used within 36 months from the date of manufacture of the drug.

Application for children

Tests regarding the use of Nebitrend in pediatrics have not been carried out, which is why it is not prescribed to this age group.

Analogues

Analogues of the drug are Nebival, Nebitenz, Nebilet with Nebivolol Orion, Nebicard with Nebivolol Sandoz, and also Nebilong and Nebivolol-Teva.