Nebilong N - instructions for use, dose, side effects, contraindications

Active substanceHydrochlorothiazide + nebivololHydrochlorothiazide + nebivolol

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Nebilong H

pills inwards

Micro Labs Limited India

Dosage form: & nbspPills.

Composition:

Each tablet contains:

Active substances: Nebivolol hydrochloride in terms of nebivolol - 5,000 mg, hydrochlorothiazide - 12,500 mg;

Excipients: lactose monohydrate 60.440 mg, microcrystalline cellulose 43.868 mg, betadec 30,000 mg, croscarmellose sodium 24,000 mg, docusate sodium -2,000 mg, povidone 5,000 mg, silicon dioxide colloidal anhydrous -2,000 mg, talc 2,000 mg, magnesium stearate - 2,000 mg.

Description:Round flat tablets white or almost white with chamfer, with a risk on one side.

Pharmacotherapeutic group:antihypertensive drug combined (beta 1-blocker selective + thiazide diuretic).

ATX: & nbsp

C.07.B.B.12 Nebivolol in combination with thiazides

Pharmacodynamics:

Niebelong H is a combined means, which includes nebivolol and hydrochlorothiazide.

Nebivolol

Nebivolol is a lipophilic cardioselective beta₁- adrenoblocker with vasodilating properties. It has antihypertensive, anti-anginal and antiarrhythmic effects. Reduces elevated blood pressure (BP) at rest, with physical stress and stress.Competitively and selectively blocks synaptic and postsynaptic bstadrenrenetceptors, making them inaccessible to catecholamines, modulates the release of endothelial vasodilating o factor nitric oxide (N0).

Nebivolol is a racemate consisting of two enantiomers: SRRR- nebivolol (Dnebivolol) and RSSSNebivolol (Lnebivolol). combining two pharmacological actions:

- D-nebivolol is a competitive and highly selective beta1-adrenoreceptor blocker (affinity for beta 1 -adrenoceptors is 293 times higher than for beta2-adrenergic receptors).

- L-nebivolol has a mild vasodilating effect by modulating the release of the relaxing factor from the vascular endothelium.

The antihypergene effect develops on the 2nd-5th day of treatment, a stable effect is observed after 1 month. This effect persists with long-term treatment. Antihypertensive effect is also due to a decrease in the activity of the renin-angiotensin-aldosterone system (does not directly correlate with changes in renin activity in blood plasma).

The use of nebivolol improves the indices of systemic and intracardiac hemodynamics. Nebivolol reduces heart rate and heart rate at rest and under physical exertion, reduces the end-diastolic pressure of the left ventricle, reduces the overall peripheral vascular resistance, improves the diastolic function of the heart (reduces the filling pressure), increases fractions ejection. Reducing the need for myocardium in oxygen (decreasing heart rate, decline preload and afterload), reduces the number and severity of angina attacks and improves the tolerance of exercise.

Antiarrhythmic effect is due to the suppression of the automaticity of the heart (including in the pathological focus) and the slowing of the atrioventricular (AV) conductivity.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions in the cortical segment of the Henle loop, without affecting its area, passing at the medulla of the kidney. It blocks carbonic anhydrase in the proximal part of the convoluted renal tubules, enhances the excretion of potassium ions, hydrocarbonates and phosphates by the kidneys. Virtually does not affect the acid-base state. Enhances excretion Icons of machine ions: It detains calcium ions in the body and inhibits the excretion of urates.

The diuretic effect develops in 1-2 hours, reaches a maximum after 4 hours,

continues to 10-12 hours. The diuretic effect decreases with decrease the glomerular filtration rate and stop at a value of less than 30 ml / min. (reduces the volume of urine and increases its concentration).

Pharmacokinetics:

Nebivolol

After oral administration nebivolol quickly absorbed from the gastrointestinal tract. Eating does not affect suction, so nebivolol can be taken regardless of food intake. Bioavailability averages 12% for nazis with "fast" metabolism and is almost complete in patients with "slow" metabolism. The effectiveness of nebivolol does not depend on the metabolic rate. Clearance in the blood plasma in most patients (with a "fast" metabolism) is achieved within 24 hours, and for hydroxy metabolites - in a few days. Concentrations in blood plasma of 1-30 mcg / l are proportional to the dose.

The connection with blood plasma proteins (mainly with albumin) for D-psbivolol is 98.1%, and for L-nebivolol, 97.9%.

Nebivolol is actively metabolized, in part with the formation of active hydroxymetabolites.Metabolized by acyclic and aromatic hydroxylation, partial N-dealkylation. The metabolic rate of nebivolol by aromatic hydroxylation is genetically determined by oxidative polymorphism and depends on the isoenzyme CYP2D6.

After the administration of 38% (the amount of unchanged active substance is less than 0.5%), the dose is excreted by the kidneys and 48% by the intestine.

In patients with "fast" metabolism, the half-life (T1 / 2) of the enantiomers of nebivolol from plasma is an average of 10 hours. In patients with "slow" metabolism, these values increase 3-5 times.

In patients with "fast" metabolism, the T1 / 2 values of the hydroxy metabolites of both enantiomers from plasma are an average of 24 hours, for the nazis with "slow" metabolism these values are approximately 2-fold increased. The pharmacokinetics of nebivolol is not affected by age and sex of patients.

Hydrochlorothiazide

When ingested, absorbed quickly, but incomplete. The time to reach the maximum concentration in the blood plasma is about 4 hours. The bioavailability of hydrochlorothiazide is 60-80%. The connection with plasma proteins is 40%.

It penetrates the placental barrier, and is excreted into breast milk. It is not metabolized. It is excreted mostly at night in unmodified form through glomerular filtration and active tubular secretion. The half-life is about 8 hours.

Indications:Arterial hypertension (patients who are shown combined therapy).

Contraindications:

- hypersensitivity to nebivolol or one of the components of the drug, as well as to other beta-blockers. hypersensitivity to hydrochlorothiazide and other sulfonamide derivatives;

- severe violations of liver function;

- acute heart failure;

- cardiogenic shock:

- chronic heart failure in the stage of decompensation (requiring inotropic therapy):

- syndrome of weakness of the sinus node, including sinoatrial block;

- atrioventricular blockade of II and III degree (without artificial pacemaker):

- severe forms of bronchial asthma and chronic obstructive pulmonary disease (COPD);

- pheochromocytoma (without simultaneous use of alpha-blockers);

- depression;

- metabolic acidosis;

- bradycardia (heart rate less than 60 bpm);

- severe arterial hypotension (systolic blood pressure less than 90 mm pt st)

- severe violations of peripheral circulation ("intermittent" lameness, Raynaud's syndrome);

- age under 18 years (effectiveness and safety not adopted);

- lactose intolerance, lactase deficiency or glucose-galactose malosorption (the preparation contains lactose);

- simultaneous administration with floktaphenin, sultopride (see Interactions with other drugs);

- hypovolemia;

- hard-to-control diabetes mellitus;

- acute renal insufficiency;

- Addison's disease;

- anuria, chronic renal failure (creatinine clearance (CK) less than 30 ml / min.);

- refractory hypokalemia, hyponatremia, hypercalcemia;

Carefully:

Nebivolol

renal failure, liver disorders, diabetes mellitus, hyperthyroidism, bronchospasm episodes in history, allergic diseases (possibly increased sensitivity to allergens, weighting allergic reactions and reduced therapeutic response to adrenalin), psoriasis, atrioventricular block I degree, Prinzmetal angina, COPD , in elderly patients (over 65 years),peripheral atherosclerosis, pheochromocytoma (against the background of therapy with alpha-blockers).

Hydrochlorothiazide

atrioventricular blockade of the 1st degree, ischemic heart disease, hepatic insufficiency. renal failure (QC more than 30 ml / min.); thyrotoxicosis, pheochromocytoma (against the background of treatment with alpha-adrenoblockers), water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia); depression (including in the anamnesis), myasthenia gravis, gout, psoriasis, advanced age, simultaneous reception of cardiac glycosides.

Pregnancy and lactation:

Nebivolol

In pregnancy, the drug is prescribed only on strict indications, when the benefit to the mother exceeds the risk for the fetus (in connection with the possible development of a newborn bradycardia, arterial hypotension, hypoglycemia and respiratory paralysis). Treatment should be interrupted for 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict observation of the newborn within 48-72 hours after delivery.

There is no data on the isolation of nebivolol in breast milk. Therefore, the drug is not recommended for women during lactation. The drug was administered nebivolol during lactation it is necessary, then breastfeeding should be discontinued.

Hydrochlorothiazide

Hydrochlorothiazide penetrates the placental barrier. Contraindicated use of the drug in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the drug can be prescribed only in case of acute necessity, when the benefit to the mother exceeds the potential risk to the fetus and / or the child. There is a danger of fetal or neonatal jaundice, thrombocytopenia and other consequences.

Hydrochlorothiazide penetrates into breast milk; therefore, if the use of the drug is absolutely necessary, then breast-feeding should be discontinued.

Dosing and Administration:

Inside, it is desirable to take at the same time, 1 time per day, regardless of the time of ingestion, without chewing and drinking with a sufficient amount of liquid. At the beginning of therapy should take 1 tablet a day.

If the therapeutic effect is not enough, after 2 weeks the dose can be increased to 2 tablets.

The maximum daily dose is 2 tablets per day.

Patients with severe impairment of liver function and impaired renal function (QCless than 30 ml / min), the use of the drug is not recommended (see the section "Contraindications").

Side effects:

Nebivolol

The frequency of side effects is presented in the following gradation: very often (10%), frequent (more than 1% and less than 10%), rare (more than 0.1% and less than 1%), rare (more than 0.01% and less than 0.1 %), very rarely (less than 0.01%). including individual messages.

From the nervous system:

Often: headache, dizziness, fatigue, weakness, paresthesia;

Infrequently: depression, bright dreams, confusion, insomnia;

Rarely: syncope, hallucinations, amnesia.

From the gastrointestinal tract:

Often: nausea, constipation, diarrhea;

Infrequently: flatulence, indigestion, vomiting.

From the cardiovascular system:

Infrequently: bradycardia, cardiac failure, heart block, orthostatic hypotension, peripheral circulatory disturbances (sensation of "cold" in the extremities, cyanosis), shortness of breath, heart rhythm disorders, Reynaud's syndrome, peripheral edema, cardialgia, aggravation of chronic heart failure, marked reduction in blood pressure.

From the skin:

Infrequently: skin rash erythematous, itchy skin. hyperemia cutaneous integuments;

Rarely: aggravation of psoriasis, alopecia:

In some cases: angioedema.

From the respiratory system:

Infrequently: bronchospasm (including in the absence of obstructive lung disease history), bronchospasm in patients with bronchial asthma or obstruction respiratory tract in the anamnesis.

Other: photodermatosis, hyperhidrosis, visual impairment (dry eyes), sexual dysfunction.

Hydrochlorothiazide

Violation of the water-electrolyte balance

- Hypokalemia, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis: dryness of the oral mucosa, thirst, irregular heart rhythm, lability of mood or psyche, cramps and muscle pains, nausea, vomiting, unusual fatigue or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

- Hyponatremia: confusion, convulsions, slowing down the process of thinking, increased fatigue, increased excitability, convulsions, lethargy.

Metabolic phenomena: hyperglycemia, glucosuria, hyperuricemia with exacerbation of gout.

Treatment with thiazides can reduce glucose tolerance and latent diabetes mellitus can manifest. When high doses are used, lipid concentrations in the blood serum can increase.

From the digestive tract: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the cardiovascular system: arrhythmias, orthostatic hypotension, vasculitis.

From the nervous system: dizziness, temporarily vague vision, headache, paresthesia.

From the hematopoiesis: (very rarely): leukopenia, agranulocytosis. thrombocytopenia, hemolytic anemia, aplastic anemia.

Allergic reactions: urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.

Other phenomena: decreased potency, impaired renal function, interstitial nephritis.

Overdose:

Nebivolol

Symptoms: marked decrease in blood pressure.bradycardia. severe intracardiac conduction, shock, asystole, respiratory arrest, bronchospasm, unconsciousness, convulsions, coma, nausea, vomiting, cyanosis, hypoglycemia, hyperkalemia, Treatment: gastric lavage, reception of activated charcoal, In the case of a marked decrease in blood pressure, it is necessary to give the patient a horizontal position with raised legs, if necessary with / in the administration of liquid and vasopressors.

With bradycardia, enter / in 0.5-2 mg of atropine. in the absence of a positive effect, a transvenous or virotricide artificial pacemaker can be staged. When AV blockade (II-W), intravenous administration of beta-adrenomimetics is recommended; if they are ineffective, consider the establishment of an artificial pacemaker. With heart failure treatment begins with the introduction of cardiac glycosides and diuretics, in the absence of effect, it is advisable to administer dopamine, dobutamine or vasodilators. When bronhospazme enter intravenously beta2-adrenomimetiki. With convulsions, intravenous diazepam.

With ventricular extrasystole lidocaine (antiarrhythmic drugs of class 1A can not be administered).

Hydrochlorothiazide

The most noticeable manifestation of hydrochlorothiazide overdose is the acute loss of fluid and electrolytes, expressed in the following signs and symptoms: tachycardia, marked decrease in blood pressure, shock, weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, impaired consciousness, increased fatigue. chociota, vomiting, thirst, polyuria, oliguria or anuria (due to hemoconcentration), hypokalemia, hyponatremia, hypochloraemia, alkalosis, increased urea nitrogen in the blood (especially in patients with renal insufficiency).

Treatment: there is no specific antidote.

Induction of vomiting, gastric lavage, reception of activated charcoal. In the case of a marked decrease in blood pressure or shock, the volume of the circulation should be compensatedpthe blood (bcc) and electrolytes (potassium, sodium).

Required control of water-electrolyte balance (especially the content of potassium in the blood serum) and the function of the nights.

Interaction:

Nebivolol

Floktaphenin in the case of shock or arterial hypotension caused by floktaphenin, beta-adrenoblockers weaken the compensatory mechanisms of the cardiovascular system,

Sultopride: increased risk of ventricular arrhythmia, especially as pirouette.

With the simultaneous use of beta-adrenoblockers with blockers of "slow calcium channels (BCC) (verapamil and diltiazem) the negative effect on myocardial contractility and AV conductivity. Ppotivo shown in / in the introduction of verapamil on the background of nebivolol. With simultaneous use with antihypertensive drugs, nitroglycerin or CMCC can develop severe arterial hypotension (special caution is necessary when combined with prazosin). When used simultaneously with antiarrhythmic drugs, the risk of cardiodepressive action and bradycardia increases when combined with any antiarrhythmic drug. Amiodarone also increases the risk of atrioventricular blockade. The risk of ventricular arrhythmia caused by sotalol is increased by amiodarone, dronedarone, procainamide and quinidine (avoid joint application).

With the simultaneous use of nebivolol with cardiac glycosides, no increase in the effect on slowing AV conductivity.

Simultaneous use of nebivolol and preparations for general anesthesiacan cause suppression of reflex tachycardia and increase the risk of developing arterial hypotension.

Clinically significant interactions of nebivolol and nonsteroidal anti-inflammatory drugs (NSAIDs) not installed. Acetylsalicylic acid as an antiplatelet agent can be used concomitantly with nebivolol.

Glucocorticosteroids and estrogens, gestagens weaken the antihypertensive effect of beta adrenoblockers.

Simultaneous the use of tricyclic antidepressants, barbiturates and derivatives of phenothiazine, ethanol, anxiolytics, hypnotics can enhance the antihypertensive effect of nebivolol.

Allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving nebivolol.

Iodine-containing radiopaque agents for intravenous administration increase the risk of anaphylactic reactions.

Pharmacokinetic interaction

When used simultaneously with drugs that inhibit the reuptake of serotonin, or by other means,biotransforming with the participation of isoenzyme СУР2D6. Nebivolol metabolism slows down, which can lead to a risk of bradycardia. With simultaneous application nebivolol no impact on the pharmacokinetic parameters of digoxin.

With simultaneous application with cimetidine, the concentration of nebivolol in the blood plasma increases (there are no data on the effect on the pharmacological effects of the drug). The simultaneous use of ranitidine did not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardinine, concentrations of active substances in the blood plasma increased slightly, but this is not clinically relevant.

Simultaneous administration of ethanol, furosemide or hydrochlorothiazide did not affect the pharmacokinetics of nebivolol.

Clinically significant interactions of nebivolol and warfarin have not been established.

With simultaneous application of sympathomimetic agents suppress activity

nebivolol.

When combined with nebivolol with insulin and hypoglycemic agents for oral administration, symptoms of hypoglycemia (tachycardia, tremor) can be masked. Hydrochlorothiazide

Simultaneous application with:

- Lithium salts (renal clearance of lithium decreases, its toxicity increases). Use with caution with the following preparations:

- hypotensive drugs (their effect is potentiated, there may be a need for dose adjustment)

- cardiac glycosides (giokalemia and hypomagnesemia, associated with the action of thiazide diuretics, may increase the toxicity of cardiac glycosides)

- amiodarone (its use simultaneously with thiazide diuretics can lead to an increased risk of arrhythmias associated with hypokalemia)

- hypoglycemic agents for oral administration (their effectiveness decreases, hyperglycemia may develop)

- corticosteroid drugs, calcitonin (increase the degree of excretion of potassium)

- NSAIDs (can weaken the diuretic and antihypertensive effect of thiazides) with nondepolarizing muscle relaxants (their effect may be enhanced)

- amantadine (clearance of amantadine may be reduced by hydrochlorothiazide, which leads to an increase in the concentration of amantadine in blood plasma and possible toxicity)

- colestyramine, which reduces the absorption of hydrochlorothiazide.

- ethanol, barbiturates and narcotic drugs, which increase the risk of orthostatic hypotension.

Special instructions:

The abolition of beta-blockers should be carried out gradually, within 10 days to 2 weeks in patients with ischemic heart disease.

Control of blood pressure and heart rate at the beginning of the drug should be daily.

Older patients need control of kidney function (1 time in 4-5 months).

With angina pectoris, the selected dose of the drug should provide heart rate in

rest within the limits of 55-60 ud./min., at a load no more than 110 ud./min.

Patients using contact lenses should take into account that the use of beta-blockers may reduce the production of tear fluid. Nebivolol does not affect the concentration of glucose in blood plasma in patients with diabetes mellitus. Nevertheless, care should be taken when treating these natsmen. because the nebivolol can mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents. Control of the concentration of glucose in the blood plasma should be carried out once in 4-5 ms. (in patients with diabetes mellitus).

Beta-adrenoblockers should be used with caution in patients with COPD, as bronchospasm may worsen.

With hyperfunction of the thyroid gland, the drug levels tachycardia. The effectiveness of beta-blockers in smokers is lower than in non-smoking patients. Against the background of beta-adrenoblokagorami therapy may exacerbate the course of psoriasis. Patients with this disease Nebilong H should be administered with caution. During the period of therapy with Nebilong H, it is necessary to monitor the acid-base state and the content of electrolytes (potassium, sodium, calcium). With prolonged course treatment, it is necessary to closely monitor the clinical symptoms of water-electrolyte balance disorders, in the first place. \ patients at high risk: patients with diseases of the cardiovascular system and violations of liver function; in case of severe vomiting or when signs of disturbance of the water-electrolyte balance appear, such as dryness of the mucous membrane of the cavity, thirst, weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, arterial gynotension, oliguria, tachycardia, complaints from the side gastrointestinal tract.

Hypokalemia can be avoided by the use of potassium-containing drugs or a potassium-rich crop (fruits, vegetables), especially in case of increased potassium loss (increased diuresis, prolonged treatment) or simultaneous treatment with cardiac glycosides or corticosteroid drugs.

It is shown that thiazides increase the excretion of magnesium by the kidneys; this can lead to hypomagnesemia.

With reduced renal function, control of creatinine clearance is required. In such patients, the drug can cause azotemia, and cumulative effects can also develop. If the violation of kidney function is obvious, when oliguria comes, one should weigh the possibility of drug cancellation. Patients with impaired liver function or with progressive liver diseases should be cautioned with thiazides, since a small disturbance of the water-electrolyte balance, as well as the content of ammonium in the serum, can cause hepatic coma.

In patients with peripheral circulatory disorders, caution should be exercised when prescribing Nebilong N.

Alcohol, barbiturates, narcotic drugs intensify the orthostatic hypotensive effect of thiazide diuretics.

Thiazides can reduce the amount of iodine that binds to blood serum proteins without manifesting signs of thyroid dysfunction (due to hydrochlorothiazide).

Patients with pheochromocytoma should not be prescribed Nebelong H until treatment with alpha-blockers is prescribed. In this case, it is necessary to monitor blood pressure. It is recommended to stop Nebilong H with the development of depression caused by taking the beta-blocker (due to the content of nebivolol in it). Particular attention is required in cases of surgical intervention under general anesthesia in patients taking beta-blockers. Such Nazis should abolish Nebilong N 48 hours before surgery, warn the anesthesia doctor. that the patient takes the drug Nebilong I. As a means for general anesthesia, a drug with a minimum negative inotropic effect should be chosen. With a history of anaphylactic reactions, regardless of the cause of their occurrence, especially when conducting desensitizing therapy, treatment with Nebilong H (due to the content of nebivolol in it) can increase the risk of allergic reactionsand promote the development of resistance to epinephrine (adrenaline) treatment in usual doses.

In patients with hyperuricemia, the risk of developing attacks of gout aggravation is increased. In this case, the dose of Nebilong H should be selected individually under the control of the concentration of uric acid in the blood serum. Before the study of the function of parathyroid glands, the treatment with Nebilong H should be stopped, as transient hypercalcemia may occur on the background of its administration.

Effect on the ability to drive transp. cf. and fur:

During the period of therapy, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 12.5 mg + 5.0 mg.

Packaging:10 tablets per blister from Al / Al. For 1, 3. 5 or 10 blisters together with instructions but in a cardboard box.

Storage conditions:In a dark place at a temperature of no higher than 25 ° C \ Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001276

Date of registration:25.11.2011

Date of cancellation:2016-11-25

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspMICRO LABS LIMITED MICRO LABS LIMITED India

Information update date: & nbsp10.01.2016

Illustrated instructions

Instructions

Nebilong H (Nebilong N)