Nebilet Nebivolol 5mg Menarini treatment for hypertension and chronic heart failure (2 blisters x 14 tablets)

Dosage form Box of 2 blisters x 14 tablets
Specifications Nebivolol

Ingredient

Composition informationContent
Nebivolol5mg

Uses

indications

Nebilet drug indicated in the following cases:

  • Hypertension: Treatment of idiopathic hypertension.

    ATC code: C07AB12.

    Nebivolol is a mixture of two types of optical isomers, SRRR-nebivolol (or D-nebivolol) and RSSS-Nebivolol (or L-Nebivolol). The drug combines two pharmacological effects:

    It is a selective and competitive beta receptor receptor: This effect is of SRRR-Enantiomer isomers (D-Enantiomer).

    It has a lightweight stretching properties due to interaction with the L-Arginine/Nitric Oxide NO road.

    Use nebivolol single dose or repeat dose to reduce heart rate and lower blood pressure when resting and when exercising, in people with normal blood pressure and patients with hypertension. Hypotension effect is maintained when long -term treatment.

    In the treatment dose, Nebivolol has no antagonistic effect on the alpha-adrenergic system.

    During the short treatment and long -term treatment with Nebivlol for patients with hypertension, body resistance decreases. Although the heart rate decreases, the cardiac amount when resting and when physical activity is not hill due to increasing the volume of the squeeze. Clinical studies on hemodynamic differences when compared to other beta receptor antagonists have not been fully set.

    For patients with hypertension, Nebivolol increases the vascular stretching of NO intermediaries for acetylcholine, which is usually reduced in endothelial dysfunction patients.

    Regarding mortality and disease rates, in a clinical trial compared to the placebo, on 2128 patients ≥ 70 years old (the average age is 75.2) with chronic heart failure stable or without decreased blood rate of left ventricle (LVEF average: 36 ± 12.3%, with the following distribution: LVEF 45% in 19% of patients) are monitored for an average of 20 months, Nebivolol, belonging to the best therapeutic group, prolonged the death of death or hospitalized for cardiovascular reasons with a relatively 14% risk reduction rate (absolute risk reduction rate of 4.2%). The risk of decrease after 6 months of treatment and maintenance during treatment (average is 18 months). The effectiveness of Nebivolol does not depend on the age, gender or LVEF of the research object. Benefits of reducing death due to no different causes are statistically significant when compared to placebo (reducing absolute death rate 2.3%).

    The rate of death decreases when treating Nebivolol for patients (4.1%compared to 6.6%, relatively 38%decrease).

    In vitro and in vivo tests in animals show that Nebivolol has no effect of endogenous sympathy (Intrinsic Sympathicomimetic Activity).

    In vitro and in vivo tests in animals show that Nebivolol is used in pharmacological doses without membrane stability.

    In healthy volunteers, Nebivolol does not have a significant impact on maximum effort or durability.

    Clinical and preclinical evidence existing in patients with hypertension does not show that Nebivolol has an adverse effect on erectile function.

    pharmacokinetics

    Nebivolol optical isomers are absorbed quickly after drinking. Nebivolol's absorption is not affected by food; Nebivolol can be used or not with food.

    Nebivolol is widely metabolized, largely into activated hydroxy metabolites. Nebivolol is metabolized through the saturated and aromatic cyclic cyclicization, reducing alkyl and glucuronide, in addition, glucuronide of hydroxyl metabolites is also formed. Nebivolol's metabolites by hydroxylation of aromatic rings due to enzyme CYP2D6 depend on genetic oxidation. The average bioavailability of Nebivolol after drinking is 12% with fast metabolites and almost entirely with poor metabolites.

    In the same stable state and the dose is the same, the peak concentration of Nebivolol's plasma does not change in poor metabolic form with a concentration of about 23 times higher than in the form of rapid metabolism. When comparing drugs that have not metabolized and active metabolites, the difference in the peak concentration in plasma is 1.3 - 1.4 times. Because of the difference in metabolic speed, Nebilet dose is always adjusted for each patient object: those who are less than a lower dose.

    With fast metabolites, the semi -elimination time of nebinolol isomers is 10 hours. With slow metabolites, the time will last 3-5 times. When rapid metabolism, the plasma concentration of the RSSS isomer is slightly higher than the SRRR isomer. When the metabolism is slow, this difference will be greater. When rapid metabolism, the half -life of the hydroxyl metabolites of the two types of isomer is 24 hours, and when the metabolism is slow, this time lasts 2 times.

    In most research objects (fast metabolic form) of plasma concentrations in a stable state within 24 hours for nebivolol and a few days for hydroxyl metabolites.

    Plasma concentration in plasma is proportional to the dose from 1mg to 30mg. Nebivolol's pharmacokinetics are not affected by age.

    In plasma, both optical isomers of Nebivolol are mainly connected to albumin.

    The cohesion with plasma proteins is 98.1% for SRRR isomers and 97.9% for RSSS isomers.

    A week after the drug, 38% of the dosage excreted in the urine and 48% excreted in feces. Nebivolol excreted urine in the form of no metabolism under

    Clinical safety data

    Prelisors shows that Nebivolol is not at risk of special harm to people based on conventional studies on genetic toxicity, reproductive ability and development and cancer. Adultery effects on reproductive function are only recorded at high doses, exceeding many times compared to the maximum recommended dose for people.

  • Before taking Nebilet Nebivolol 5mg Menarini treatment for hypertension and chronic heart failure (2 blisters x 14 tablets)

    How to use

    Nebilet drugs for oral use

    Nebilet can be taken during meals.

    Dosage

    Hypertension

    Adults

    Use 1 tablet/day (5 mg), preferably oral at the same time per day.

    Hypotension effects will be clear after 1-2 weeks of treatment. Sometimes, the maximum efficiency is only achieved after 4 weeks.

    Coordinate with other anti -hypertension drugs

    Beta inhibitors can be used alone or in combination with other hypertension medications. So far, the effectiveness of hypotension has been enhanced when Nebilet 5 mg is in combination with hydrochlorothiazide 12.5 - 25 mg.

    Patients with renal failure

    For patients with renal failure, the initial starting dose is 2.5 mg/day. If necessary, the dose can be increased to 5 mg/day.

    Patients with liver failure

    Data for patients with liver dysfunction or liver failure is limited. Therefore, contraindicated use of Nebilet for these patients.

    Elderly

    In patients over 65 years old, the starting dose is 2.5 mg/day. If necessary, the dose can be increased to 5 mg. However, there is little experience in using drugs for patients over 75 years old, must be cautious and strict control when taking drugs for this group of patients.

    Children

    There is no data on Nebilet's safety and effectiveness in children and teenagers under 18 years old. Therefore, do not recommend taking medicine for children and teenagers.

    chronic heart failure

    To treat chronic heart failure stability, the dose should be increased slowly until the optimal dose for each patient.

    Patients with stable chronic heart failure are patients who do not suffer from acute heart failure occurred within 6 weeks. The treatment doctor must be experienced in the treatment of chronic heart failure.

    For patients who are taking cardiovascular medications, including diuretics and/or digoxin and/or ACE enzyme inhibitors and/or Angiotensin II antagonists, should maintain the dose of these drugs for 2 weeks before starting treatment with Nebilet.

    Adjustment increasing the dose should be conducted every step later, with the distance between the dose increase is 1-2 weeks depending on the response of the patient:

    1.25 mg Nebivolol, up to 2.5 mg of Nebivolol used once a day, then 5 mg x 1 time/day, then 10 mg x 1/day.

    The maximum dose is 10 mg x 1 time/day.

    When starting to treat and every time the dose increases should be closely monitored by an experienced doctor for at least 2 hours to ensure that clinical states are still stable (namely blood pressure, heart rate, conduction disorders, signs of severe heart failure).

    The appearance of unwanted side effects can make patients unable to be treated at maximum dose. If necessary, the maximum dose can also decrease step by step and re -use the appropriate dose.

    During the dose adjustment process, if the heart failure is worse or the patient is intolerant to the drug, the first is to reduce the dose of Nebivolol or stop the drug immediately if necessary (in case of severe hypotension, more severe heart failure accompanied by acute pulmonary edema, heart shock, symptom heart rate, atrial bloc).

    Treatment of chronic heart failure with Nebivolol is often long -term treatment.

    Do not stop treating Nebivolol suddenly because it can lead to a worse heart failure. If stopping the drug is necessary, it is necessary to reduce the dose slowly every week.

    Patients with renal failure

    No need to adjust the dose for patients with mild to medium mild renal impairment because the maximum increase is adjusted to each patient. There is no experience in treating patients with severe renal impairment (serum creatinine ≥ 250 µmol/l). Therefore, Nebivolol should not be used for these patients.

    Patients with liver failure

    Data for patients with liver failure is limited. Therefore contraindicated use of Nebilet for these patients.

    Elderly

    No need to adjust the dose because the maximum tolerance has been adjusted for each patient.

    Children

    There is no data on Nebilet's safety and effectiveness in children and teenagers under 18 years old. Therefore, do not recommend taking medicine for children and teenagers.

    Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What do

    do when using overdose?

    Symptoms

    Symptoms of overdose when using beta inhibitors are: slow heart rate, hypotension, bronchospasm and acute heart failure.

    Treatment

    In case of overdose or hypersensitivity, the patient must be closely monitored and treated at the Department of Active Care. Should check blood sugar levels. The absorption of the remaining medication in the stomach can be prevented by gastrointestinal and active carbon or laxative. Artificial respiration can sometimes be required. Bradycardia or vagus reaction can be treated by using atropine or methylatropine. Hypotension and shock can be treated by plasma infusion/or plasma replacement solutions and if can use catecholamine.

    The effect of beta inhibitors can be antagonistic by being slow intravenous transmission isoprenaline hydrochloride, starting at a dose of about 5 Ug/min, or Dobutamine, starting at a dose of about 2.5 µg/minute, until the required effect is achieved. If the required effect is still required, isoprenaline can be used with dopamine. If the desired effect has not been achieved, Glucagons intravenously can be considered at a dose of 50 - 100 µg/kg. If necessary, the injection repeats within 1 hour, then, if necessary, the glucagon 70 intravenously can be transmitted µg/kg/h. In some rare cases of anti -treatment heart rate, the pacemaker can be used.

    In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

    What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

    Side Effects

    The other undesirable effects listed below are independent of the effect of lowering blood pressure and chronic heart failure because there is a difference in accompanying pathological condition.

    Hypertension

    The unwanted effects have been reported, most of the cases are light to medium, listed in the table below, classified by body systems and frequency order:

    Agency system

    popular

    (≥ 1/100 -

    Unsatisfactory

    (1/1,000 -

    Very rare

    (≤ 1/10,000)

    Feeling
    return) Vomus, vomiting force
    Flipped, cold/cyanotic, Raynaud's syndrome, dry eyes, toxicity on Practolol eye mucosa.

    Chronic heart failure

    Data on unwanted effects for patients with heart failure are statistically made from a clinical trial compared to placebo over 1067 patients using Nebivolol and 1061 patients with placebo. In this study, there were a total of 449 patients using Nebivolol (42.1%) with unwanted effects that could be related to drug use compared to 334 patients using placebo (31.5%). Unwanted effects mainly in patients using Nebivolol are slow and dizziness, occurring in about 11% of patients. The frequency corresponding to the placebo group is about 2% and 7%.

    The rate of unwanted effects is listed below (capable of drug use), especially related to patients treated with chronic heart failure.

    Heart failure is more severe occurring in 5.8% of patients using Nebivolol compared to 5.2% of patients with placebo.

    Hypotension is reported in 2.1% of patients using Nebivolol compared to 1.0% of patients using placebo.

    Integrated drugs are reported in 1.6% of patients using Nebivolol compared to 0.8% of patients with placebo.

    Atrial-level 1-level bloc is reported in 1.4% of patients using Nebivolol compared to 0.9% of patients using placebo.

    The lower limb is reported in 1.0% of patients using nebivolol compared to 0.2% of the placebo.

    Report cases suspected of harmful reactions

    Reporting cases suspected of harmful reactions after licensing of drug circulation is important. This allows to monitor the balance between the benefits/risks of the drug. Health workers are required to report any case of suspicion of a harmful reaction through the national reporting system.

    Warnings

    Before using the drug you need to read the instructions carefully and refer to the information below.

    contraindicated

    Nebilet drugs contraindicated in the following cases:

  • Hypersensitivity to active ingredients or any excipients.

    In addition, like other beta inhibitors, contraindicated use of Nebilet in the following cases:

  • Sinus node impairment syndrome, including sinus - atrial bloc. At the beginning of treatment).

    Caution when using

    The following caution and warnings are applied to all beta inhibitors in general:

    Anesthesia

    Continue treatment with beta inhibitors reduces the risk of arrhythmia during anesthesia and intubation. If you stop taking beta inhibitors before surgery, it should be stopped at least 24 hours earlier.

    Be cautious when using some anesthesia because it can reduce myocardial strength.

    Atropine intravenous injection can help patients avoid the vagus reaction.

    Cardiovascular

    In general, beta inhibitors should not be used for patients with congestive heart failure, unless untreated, unless the heart failure has been stable.

    For patients with ischemic heart anemia, the treatment with beta inhibitors should be stopped slowly, for example, over 1-2 weeks. If necessary, should start treatment with other drugs at the same time to stop the drug to avoid overeating chest pain.

    Beta inhibitors may slow down the heart rate. If the heart rate is below 50 - 55 BPM when resting and/or patients with symptoms suggesting the slow heart rate, the dose should be reduced.

    Should use beta inhibitors with the following caution:

    In patients with peripheral circulatory disorders (Raynaud's disease or syndrome, limp), because these disorders may be more serious.

    In patients with cardiac grounds 1, because of the effect of slowing the transmission time of beta inhibitors.

    In patients with Prinzmetal angina due to the effect of alpha receptor antagonism causing coronary spasms; Beta inhibitors may increase the frequency and time of angina.

    In general, the coordination between Nebivolol with Calcium inhibitors of Verapamil and Diltiazem groups, anti -arrhythmic drugs group I, antihypertensive drugs acting on the central is not recommended.

    Metabolism/endocrine

    Nebilet does not affect blood sugar levels in diabetes patients.

    However, caution when taking drugs for patients with diabetes because Nebivolol can cover some signs of hypoglycemia (such as fast heartbeat, chest drum).

    Beta inhibitors can cover heart beat symptoms in patients with hyperthyroidism.

    Sudden stopping of drugs may increase symptoms.

    Respiratory

    In patients with chronic obstructive pulmonary disease, beta inhibitors can be used but must be cautious because it may increase respiratory spasms.

    Other

    Patients with a history of psoriasis are only used for beta inhibitors when they have considered the kidneys.

    Beta inhibitors can cause increased sensitivity to allergens and worsen hypersensitivity reactions.

    It is necessary to control regularly at the beginning of the treatment of chronic heart failure with Nebivolol. Do not suddenly stop pesticides when indicated clearly.

    This drug contains lactose. Patients with genetic (rare) Galactose intolerance, Lapp-Lactase deficiency or Glucose-Galactose should not take this drug.

    The effect of the drug on the ability to drive and operate machinery

    There has been no research and effects of the drug on the ability to drive and operate machinery. Pharmacological studies show that Nebilet 5 mg does not affect mental function. When driving and operating machinery, attention should be paid that dizziness and fatigue can sometimes occur.

    Use drugs for women during pregnancy and lactation

    Used for pregnant women:

    Nebivolol can be harmful to pregnancy and/or fetus/infant. In general, beta inhibitors reduce the circulatory flow through the placenta, so the fetus is underdeveloped, the fetal death, miscarriage or early labor. Other unwanted side effects (eg hypotension and slow heart rate) may occur for fetus and infants. If the treatment with beta inhibitors is necessary, it is advisable to use selective inhibitors on the beta receptor 1.

    Do not use nebivolol during pregnancy unless really necessary. If the treatment with Nebivolol is necessary, it is necessary to closely monitor the blood flow to the uterus - each other and the development of the fetus. In case of harm to the mother and the fetus, it is advisable to consider using other drugs. Babies must be closely monitored. Symptoms of hypotension and slow heart rate often occur in the first 3 days.

    Use drugs for breastfeeding women:

    Animal studies show that Nebivolol is excreted through milk. On the body, it is unknown whether this drug will be secreted into the mother's milk or not. Most beta inhibitors, especially fat -soluble preparations like Nebivolol and its active metabolites excrete in breast milk, although different levels. Due to the could not rule out risks for infants/young children, mothers who are using nebivolol should not breastfeed.

    Reproduction:

    Nebivolol does not affect the mouse's fertility except at a much higher dose than the maximum recommended dose for people when observing the side effects on the reproductive organ of the rats and rats in both males and females. The influence of nebivolol on human fertility has not been known.

    Drug interaction

    Pharmacological interaction

    The following interactions are applied to beta inhibitors in general.

    Do not be proposed:

    It is necessary to control regularly at the beginning of the treatment of chronic heart failure with Nebivolol. Do not suddenly stop pesticides when indicated clearly.

    This drug contains lactose. Patients with genetic (rare) Galactose intolerance, Lapp-Lactase deficiency or Glucose-Galactose should not take this drug.

    interact with other drugs or other types of interactions

    Pharmacological interaction

    The following interactions are applied to beta inhibitors in general.

    Do not be proposed:

    Group I anti -arrhyths (Quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone): Slow atrial transmission time and reduce the contraction of myocardial muscle contraction.

    Verapamil/ditiazem calcium inhibitors: reduce the heart muscle contraction and inhibit the atrial - ventricular conduction. Verapamil intravenous injection for patients being treated with beta inhibitors can lead to excessive hypotension and atrial - ventricular bloc.

    Hematoplasty drugs acting on the middle (clonidine, guanfacin, moxonidine, methyldopa, rilmenidine): The combination of simultaneous use with blood pressure drugs acting on the central can worsen the heart failure due to reducing the force of the central sympathetic nervous nervous nervous nervous nervous nervousness (reducing the heart rate and cardiac output, sudden stops, if it has stopped using the previous medication, if it has stopped using the previous inhibition of inhibitors. Beta, which can increase the risk of "hypertension backward".

    Cautions must be cautious:

  • Anti -arrhythmia group III (amiodarone): can affect the time of the atrial - ventricular. Simultaneous use of beta inhibitors and anesthesia can reduce reflected tachycardia and increase the risk of hypotension. According to the general principle, avoid sudden stops of beta inhibitors. Anesthesia should be notified to the patient who is taking Nebilet. Simultaneously with medication for hypertension causes increased hypotension effect, therefore should adjust the dose of antihypertensive drugs.
  • The combination should consider:

  • Supported glycosides: simultaneous use can increase the time of the atrial - ventricular transmission. Clinical studies with Nebivolol does not show any clinical evidence of drug interactions. Nebivolol does not affect Digoxin's dynamics. Patients with heart failure. Cuong sympathize: simultaneous use may lose the effect of beta inhibitors. Beta inhibitors can stimulate Alpha adrenergic effects of sympathetic drugs with both alpha and beta - adrenergic system (risk of hypertension, bradycardia and cardiac bloc).
  • Pharmacokinetic interactions

    Because the metabolism of Nebivolol contacts the ISOENZYM CYP2D6, therefore, the use of drugs simultaneously with these enzyme inhibitors, especially Paroxetine, Fluoxetine, Thioridazine and Quinidine may increase Nebivolol levels in plasma, increasing the risk of excessive slow heart rate and other undesirable side effects.

    Use Nebivolol simultaneously with cimetidine, increasing the concentration of Nebivolol in plasma but does not change the effect on the forest. Simultaneous use with Ranitidine does not affect the pharmacokinetics of Nebivolol. As long as taking Nebilet during meals, or using antacids between meals, these two drugs can be used together.

    Nebivolol combination with nicardipine increases the concentration of both drugs in plasma but does not change the clinical effect. Using drugs with alcohol, Furosemide or hydrochlorothiazide does not affect the pharmacokinetics of Nebivolol. Nebivolol does not affect the pharmacokinetics and pharmacology of Warfarin.

    Storage

    Store at a temperature not exceeding 30 ° C in the original packaging, avoid moisture and avoid light.

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