OD-Neb - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate - 83.45 mg, corn starch - 18.00 mg, croscarmellose sodium - 5.40 mg, polysorbate 80 - 0.22 mg, hypromellose - 1.80 mg, silicon dioxide colloid - 0.23 mg, cellulose microcrystalline - 30,00 mg, magnesium stearate - 0,45 mg.

Description:Round, biconvex tablets, almost white, with a cruciform dividing risk on one side.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B.12 Nebivolol

Pharmacodynamics:

Nebivolol is a lipophilic, cardioselective third-generation beta-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 beta₁-adrenoceptors, making them inaccessible to catecholamines, modulates the release of endothelial relaxing factor of nitric oxide (N0).

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

- Dnebivolol is a competitive and, a highly selective blocker beta₁-adrenoceptors (affinity for beta₁-adrenoceptors 293 times higher than to beta₂adrenoreceptors).

- L- Nebivolol has a vasodilating effect due to the modulation of the release of the endothelial relaxing factor of nitric oxide (N0) from the vascular endothelium.

The antihypertensive effect develops on. 2-5 day of treatment, stable action is observed after 1 month. This effect persists with long-term treatment.

Antihypertensive action is also caused by 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 it cuts the heart rate (HR) 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 the ejection fraction, reduces the mass of the myocardium and the mass index of the myocardium.

Reducing the need for myocardium in oxygen (decreasing heart rate, reducing 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 automatism of the heart - (including in the pathological focus) and the slowing of the atrioventricular (AV) conductivity.

Pharmacokinetics:

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% in patients 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.

Connection with blood plasma proteins (mainly with albumin) for DNebivolol is 98.1 %, and for LNebivolol - 97.9 %.

Nebivolol, is actively metabolized, in part with the formation of active hydroxymetabolites. 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 % - through the intestines.

In patients with "fast" metabolism, the values of the half-life (T_1/2) enantiomers of nebivolol from the blood plasma averagely 10 hours. In patients with a "slow" metabolism, these values increase 3-5 times. - In patients with "fast" metabolism, the values T_1/2hydroxymetabolites of both enantiomers from blood plasma averagely 24 hours, in patients with a "slow" metabolism these values are approximately 2-fold increased.

The pharmacokinetics of nebivolol is not affected by age and sex of patients.

Indications:

- Ahyperthermia;

- ischemic heart disease (IHD): prevention of attacks of stable angina pectoris;

- chronic heart failure (CHF) (as part of combination therapy).

Contraindications:

- Hypersensitivity to nebivolol or one of the components of the drug;

- 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);

- bronchospasm and severe forms of bronchial asthma;

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

- depression;

- metabolic acidosis;

- pronounced bradycardia (heart rate less than 50 beats / min); -

- arterial hypotension;

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

- age to 18 years;

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

- simultaneous administration with floktaphenin, sultopride (see.section - "Interaction with other medicinal products").

Carefully:

FROM caution use in patients with severe renal failure (creatinine clearance (CC) of less than 20 ml / min), disorders of the liver of mild to moderate severity, diabetes, hyperthyroidism, conducting desensitizing therapy, psoriasis, atrioventricular block I degree, Prinzmetal angina, chronic obstructive pulmonary disease (COPD), in elderly patients (over 65 years).

Pregnancy and lactation:

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 reception OD-Neb drug is not recommended for women during lactation.If the use of OD-Neb during lactation is necessary, then breastfeeding should be discontinued.

Dosing and Administration:

The drug OD-Neb should be taken inside at the same time of the day, regardless of food intake, without chewing and drinking with a sufficient amount of liquid.

Arterial hypertension and ischemic heart disease

The average daily dose for the treatment of hypertension and IHD 5 mg (1 tablet) 1 time per day. The optimal effect becomes pronounced after 1-2 weeks of treatment, and in some cases - after 4 weeks. It is possible to use the drug in monotherapy, or as part of a combination therapy.

If necessary, the daily dose can be increased to 10 mg (2 tablets of 5 mg at a time). The maximum daily dose is 10 mg.

In patients with renal insufficiency, and such in patients over the age of 65 the initial dose is 2.5 mg / day (1/2 tablet of 5 mg). If necessary, increase the dose to 5 mg.

At the expressed infringements of function of kidneys (KK less than 20 ml / mines) and at patients with serious diseases of a liver the maximum daily dose makes 10 mg. Increasing the dose in these patients should be done with extreme caution.

Chronic heart failure

Treatment of chronic heart failure should begin with a gradual increase in the dose until an individual optimal maintenance dose is reached.

Selection of the dose at the beginning of treatment should be carried out - according to the following scheme, maintaining two-week intervals and based on the tolerance of this dose to the patient: a dose of 1.25 mg of OD-Neb preparation (1/4 tablets of 5 mg) once a day may be was first increased to 2.5-5 mg of OD-Neb preparation (1/2 tablets of 5 mg - 1 tablet), and then to 10 mg (2 tablets of 5 mg) once a day. The patient should be under the supervision of a doctor within 2 hours after taking the first dose of the drug, and also after each subsequent increase in the dose. Each dose increase should be carried out not later than 2 weeks. The maximum recommended dose for CHF therapy is 10 mg OD-Neb once a day. During titration, regular monitoring of blood pressure, heart rate and symptoms of CHF is recommended.

During the titration phase, in case of worsening of the course of chronic heart failure or intolerance of the drug, it is recommended to reduce the dose of OD-Neb preparation or, if necessary, to stop it immediately (in case of pronounced arterial hypotension, worsening of the course of CHF with acute pulmonary edema,in case of development of cardiogenic shock, symptomatic bradycardia or AV blockade).

Side effects:

From the nervous system: headache, dizziness, fatigue, paresthesia, depression, decreased ability to concentrate, drowsiness, insomnia, nightmarish dreams, hallucinations, confusion, fainting.

From the digestive system: nausea, constipation, weatherplasm, diarrhea, dryawn the mucous membrane of the mouth.

From the side of the cardiovascular system: bradycardia, heart failure, AV blockade, orthostatic, hypotension, disturbances, peripheral circulation, shortness of breath, heart rhythm disturbances, Raynaud's syndrome, peripheral edema, cardialgia, worsening of CHF flow¹.

From the skin: cutaneous itching, a rash of erythematous nature.

From the respiratory system: bronchospasm (including in the absence of obstructive pulmonary disease in the anamnesis), bronchospasm in patients with bronchial asthma, or airway obstruction in anamnesis, rhinitis.

Allergic Reagents: angioedema, hives, allergic vasculitis. Other: photodermatosis, hyperhidrosis, exacerbation of psoriasis, dryness, mucous membrane of the eye.

¹ - this side effect predominantly occurs during the titration of the drug dose.

Overdose:

Symptoms: nausea, vomiting, cyanosis, marked decrease in blood pressure, pronounced bradycardia, bronchospasm, AV blockade, cardiogenic shock, acute heart failure, loss of consciousness, coma, cardiac arrest.

Treatment: gastric lavage, reception of activated carbon. In the case of a pronounced reduction of blood pressure should be given to the patient a horizontal position with raised legs, if necessary, intravenously (IV), plasma-substituting solutions and vasopressors are introduced.

With severe bradycardia, I / in 0.5-2 mg of atropine is administered, in the absence of a positive effect, a transvenous artificial pacemaker is possible.

With AV blockade (II-III st.), It is recommended to inject beta-adrenomimetics intravenously, if they are ineffective, consider setting up 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 in / in beta₂-adrenomimetics.

With ventricular extrasystole - lidocaine (antiarrhythmic drugs can not be administered IA class).

Interaction:

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

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

With the simultaneous use of beta-blockers with blockers of "slow" calcium channels (BCC) (verapamil and diltiazem) increased negative effect on myocardial contractility and AV conductivity. Contraindicated in / in the administration of verapamil on the background of nebivolol. When combined with antihypertensive drugs, nitroglycerin or BCCC may develop severe arterial hypotension (special caution is necessary when combined with prazosin).

When used simultaneously with antiarrhythmic drugs of class I. and with amiodarone It is possible to enhance the negative inotropic effect and prolong the time of excitation in the atria.

With the simultaneous use of nebivolol with cardiac glycosides There was no increase in the effect on the deceleration AV conductivity.

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

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

Simultaneous application tricyclic antidepressants, barbiturates and phenothiazine derivatives can enhance the antihypertensive effect of nebivolol.

Pharmacokinetic interaction

With simultaneous application from serotonin reuptake inhibitors, or other biotransforming agents with isoenzyme CYP2D6, the metabolism of nebivolol slows down.

With simultaneous application nebivolol did not affect the pharmacokinetic parameters digoxin.

When used simultaneously with cimetidine the concentration of nebivolol in the blood plasma increases (there is no evidence of an effect on the pharmacological effects of the drug). Simultaneous application ranitideina did not affect the pharmacokinetic parameters of nebivolol.

With the simultaneous use of nebivolol with nicardipine the concentration of active substances in the blood plasma increased slightly, but this has no clinical significance.

Simultaneous reception ethanol, furosemide and hydrochlorothiazide did not affect the pharmacokinetics of nebivolol.

There is no clinically significant interaction between nebivolol and warfarin.

With simultaneous application sympathomimetic drugs inhibit the activity of nebivolol.

Special instructions:

The abolition of beta-adrenoblockers should be carried out gradually, within 10 days (up to 2 weeks in patients with coronary 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 dose of the drug should provide a heart rate at rest within 55-60 beats / min, with a load of not more than 110 beats / min.

Beta-adrenoblockers can cause bradycardia: the dose should be reduced if the heart rate is less than 50-55 beats / min (see section "Contraindications").

When deciding on the use of OD-Neb preparation in patients with psoriasis, the intended use of the drug and the possible risk of exacerbation of psoriasis should be carefully correlated.

Patients using contact lenses should take into account that the use of beta-blockers may reduce the production of tear fluid.

Before performing a surgical procedure, an anesthesiologist should be warned that the patient is taking nebivolol.

OD-Neb does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus. However, care should be taken when treating these patients, since g nebivolol can mask certain symptoms of hypoglycemia (for example, tachycardia) caused by the use of hypoglycemic agents. Control of the concentration of glucose in the blood plasma should be done 1 time per. 4-5 months.(in patients with diabetes mellitus).

Beta-blockers should be used with caution in patients with COPD, as bronchospasm may increase.

With hyperfunction of the thyroid gland, the drug levels tachycardia.

Beta-blockers may increase susceptibility to allergens and the severity of anaphylactic reactions Such patients may be immune to the usual doses of epinephrine used to stop them.

The effectiveness of beta-blockers in smokers is lower than in non-smoking patients.

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

Research work has shown that nebivolol does not affect the speed of psychomotor reactions. Pilots flying crew with arterial hypertension I degree (admitted to flight work), the drug is prescribed in an initial dose of 2.5 mg. In the future (no earlier than 2 weeks) with good tolerability of treatment and sufficient control of blood pressure, a 2.5 mg dose increase is possible. The recommended dose is 5 mg / day. Some patients may experience side effects, most often. dizziness, because of low blood pressure. If such effects occur, the patient should not drive vehicles or engage in potentially hazardous activities requiring special attention and speed of psychomotor reactions.These effects occur most often immediately after the start of treatment or with increasing doses.

Form release / dosage:

Tablets 5 mg.

Packaging:

For 10 or 14 tablets in Al / PVC blister.

For 1 or 2 blisters of 14 tablets in each, along with the instructions for use are placed in a cardboard box.

For 1 or 3 blisters, 10 tablets in each, along with instructions for use, are placed in a cardboard box.

Storage conditions:

In a dry, protected from light 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 shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001023

Date of registration:18.10.2011 / 21.06.2017

Expiration Date:Unlimited

The owner of the registration certificate:Edge Pharma Private LimitedEdge Pharma Private Limited India

Manufacturer: & nbsp

EDGE PHARMA PRIVATE, Limited India

Representation: & nbspEdge Pharma Private Limited Edge Pharma Private Limited India

Information update date: & nbsp17.06.2018

Illustrated instructions

Instructions

OD-Neb (OD-Neb)