Atenolol Belupo

General characteristics. Structure:

Active agent: атенолол 25 mg; 50 mg; 100 mg

Excipients: tablet kernel: MKTs, lactoses monohydrate, povidone, starch corn, talc, silicon dioxide colloid, croscarmellose sodium, magnesium stearate  

Tablet cover: a gipromelloza 5 спз, a gipromelloza 15 спз, talc, titanium dioxide, dinatrium of an edetat a dihydrate, wax of karnaubskiya (for tablets on 100 mg).

Pharmacological properties:

Has anti-anginal, anti-hypertensive and antiarrhytmic effect. Has no membrane stabilizing and internal sympathomimetic activity. Reduces stimulated catecholamines formation of tsAMF from ATP.
In the first 24 h after oral administration against the background of decrease in cordial emission reactive increase in the general peripheric resistance of vessels which expressiveness during 1-3 days gradually decreases is noted.
The hypotensive effect is connected with reduction of cordial emission, decrease of the activity a renin-angiotenzinovoy of system, sensitivity of baroreceptors and influence on TsNS. Hypotensive action is shown as in decrease in the systolic, and diastolic ABP, reduction of shock and minute volumes. In average therapeutic doses does not exert impact on a tone of peripheral arteries. The hypotensive effect proceeds 24 h, at regular use is stabilized by the end of the second week of treatment.
The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of ChSS (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to impact of sympathetic stimulation. Urezhayet ChSS at rest and at an exercise stress. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with chronic heart failure.
Antiarrhytmic action is shown in suppression of sinus tachycardia and is connected with elimination of aritmogenny sympathetic influences on the carrying-out system of heart, reduction of speed of spread of activation through a sinuatrial node and lengthening of the refractory period. Carrying out impulses in antegrade and to a lesser extent - in retrograde the directions through an AV node and on additional ways of carrying out oppresses.
The negative chronotropic effect is shown in 1 h after reception, reaches a maximum later 2-4 h, proceeds to 24 h.
Reduces automatism of a sinus node, urezhat ChSS, slows down AV conductivity, reduces contractility of a myocardium, reduces the need of a myocardium for oxygen. Reduces excitability of a myocardium.
At use in average therapeutic doses exerts less expressed impact on smooth muscles of bronchial tubes and peripheral arteries, than non-selective beta adrenoblockers.

Pharmacokinetics. Absorption from a GIT bystry, incomplete (50-60%). Bioavailability - 40-50%. Time of achievement of Cmax in a blood plasma - 2-4 h Badly gets through GEB, passes in insignificant quantities through a placental barrier and in breast milk. Communication with proteins of a blood plasma - 6-16%.

Practically it is not metabolized in pecheni.t1/2 - 6-9 h (increases at patients of advanced age). It is removed by kidneys by glomerular filtering (85-100% - in not changed look).

The renal failure is followed by lengthening of T1/2 and cumulation: at KK it is lower than 35 ml/min. / 1.73 of sq.m of T1/2 makes 16-27 h, at KK it is lower than 15 ml/min. / 1.73 of sq.m - more than 27 h (reduction of doses is necessary). It is removed during a hemodialysis.

Indications to use:

— arterial hypertension;
— prevention of attacks of stenocardia (except for Printsmetal's stenocardia);
— disturbances of a cordial rhythm: sinus tachycardia, prevention of supraventricular tachyarrhythmias, ventricular premature ventricular contraction;
— an acute myocardial infarction with stable hemodynamic indicators.

Route of administration and doses:

Inside, before food, without chewing, washing down with a small amount of liquid.

Arterial hypertension: treatment is begun with 50 mg of 1 times a day. Achievement of stable hypotensive effect requires 1–2 weeks of reception. At insufficient expressiveness of hypotensive effect the dose is raised to 100 mg in one step. Further increase in a dose is not recommended since it is not followed by strengthening of clinical effect.

Stenocardia: the initial dose makes 50 mg/days. If within a week do not reach optimum therapeutic effect, increase a dose to 100 mg/days.

Correction of the mode of dosing is necessary for patients of advanced age and patients with disturbances of secretory function of kidneys. In the presence of a renal failure recommend dose adjustment depending on clearance of creatinine. Patients with a renal failure, at Cl values of creatinine is higher than 35 have some / 1,73м2 (normal values make 100–150 ml/min. / 1,73 sq.m) of considerable cumulation of Atenolol Belupo does not occur.

The recommended maximum doses for patients with a renal failure are presented in the table:

Cl of creatinine, ml/min. / 1,73 sq.m	Atenolol's T1/2, h	Maximum dose of Atenolol
15–35	16–27	50 mg a day or 100 mg every other day
less than 15	more than 27	50 mg every other day or 100 mg of 1 times in 4 days

The patient who is on a hemodialysis, Atenolol Belupo appoint 50 mg/days right after carrying out each dialysis that needs to be carried out in stationary conditions since decrease in the ABP can take place.

For elderly patients: an initial single dose — 25 mg (it can be increased under control of the ABP, ChSS).

Acute myocardial infarction with stable hemodynamic indicators — 100 mg of 1 times a day or on 50 mg 2 times a day within 6–9 days or to an extract from a hospital (under control of the ABP, an ECG, glucose level in blood). Increase in a daily dose over 100 mg is not recommended since the therapeutic effect amplifies, and the probability of development of side effects increases.

Features of use:

Control of the patients accepting Atenolol Belupo has to include observation of ChSS and the ABP (in an initiation of treatment - daily, then 1 time in 3-4 months), the content of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months). At elderly patients it is recommended to monitor function of kidneys (1 times in 4-5 months).

It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS less than 50 уд. / min.

At a thyrotoxicosis атенолол can mask certain clinical signs of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology. At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers, practically does not strengthen the hypoglycemia caused by insulin and recovery of content of glucose in blood to normal concentration does not detain.

With an ischemic heart disease sharp cancellation of beta adrenoblockers can cause increase in frequency or weight of anginal attacks therefore the termination of reception of an atenolol at ischemic heart disease patients needs to be carried out gradually in patients.

In comparison with non-selective beta adrenoblockers, cardioselective beta adrenoblockers possess smaller impact on function of lungs, nevertheless, at obstructive respiratory diseases Atenolol Belupo appoint only in case of absolute indications. In need of their appointment in certain cases it is possible to recommend use of beta2-adrenomimetik.

Patients with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines, but at the same time it is necessary to watch a dosage strictly. The overdose is dangerous by development of a bronchospasm.

The special attention is necessary in cases if surgical intervention under anesthetic is required from the patients accepting атенолол. Administration of drug should be stopped for 48 h before intervention. As anesthetic it is necessary to choose drug with perhaps minimum negative inotropic effect.

At simultaneous use of an atenolol and clonidine reception of an atenolol is stopped for several days before a clonidine for the purpose of avoidance of a symptom of cancellation of the last.

Strengthening of expressiveness of hypersensitivity reaction and lack of effect of usual doses of Epinephrinum against the background of the burdened allergological anamnesis is possible.

The medicines reducing stocks of catecholamines (for example, Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of medicines have to be under constant observation of the doctor regarding identification of the expressed decrease in the ABP or bradycardia.

In case of emergence in patients of advanced age of the accruing bradycardia (less than 50 уд. / mines), arterial hypotension (systolic the ABP is lower than 100 mm hg), AV blockade, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions and kidneys it is necessary to reduce a dose or to stop treatment.

It is recommended to stop therapy at development of the depression caused by reception of beta adrenoblockers.

In case of need intravenous administration of verapamil it should be done not less than in 48 h after reception of an atenolol.

At use of an atenolol reduction of products of the lacrimal liquid is possible that matters at the patients using contact lenses.

It is impossible to interrupt sharply treatment because of danger of development of heavy arrhythmias and a myocardial infarction. Cancellation is carried out gradually, reducing a dose during 2 weeks and more (lower a dose by 25% in 3-4 days).

It is necessary to cancel before a research of content in blood and urine of catecholamines, a normetanefrin and vanililmindalny acid; credits of antinuclear antibodies.

At smokers efficiency of beta adrenoblockers is lower.

Influence on ability to driving of motor transport and to control of mechanisms
During treatment it is necessary to refrain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From cardiovascular system: development (aggravation) of symptoms of chronic heart failure (puffiness of anklebones, feet; an asthma), disturbance of atrioventricular conductivity, arrhythmia, bradycardia, the expressed decrease in the ABP, orthostatic hypotension, heartbeat, disturbance of conductivity of a myocardium, easing of contractility of a myocardium, manifestation of a vasomotor spasm (a pokholodeniye of the lower extremities, Reynaud's syndrome), a vasculitis, a stethalgia.

From TsNS and peripheral nervous system: dizziness, decline in the ability to concentration of attention, reduction in the rate of reaction, drowsiness or sleeplessness, a depression, hallucinations, increased fatigue, a headache, weakness, dreadful dreams, concern, confusion of consciousness or short-term loss of memory, paresthesia in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), muscular weakness, spasms.

From the alimentary system: dryness in a mouth, nausea, vomiting, a diarrhea, an abdominal pain, a lock, taste change.

From respiratory system: диспноэ, bronchospasm, apnoea, nose congestion.

Hematologic reactions: platelet purpura, anemia (aplastic), thrombosis.

From endocrine system: a gynecomastia, decrease in a potentiality, decrease in a libido, a hyperglycemia (at patients with a non-insulin-dependent diabetes mellitus), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Metabolic reactions: lipidemia.

Skin reactions: urticaria, dermatitis, itch, photosensitivity, strengthening to a potootda line, dermahemia, aggravation of a course of psoriasis, reversible alopecia.

Sense bodys: vision disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis.

Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.

From laboratory indicators: agranulocytosis, leukopenia, increase in activity of liver enzymes, hyperbilirubinemia, thrombocytopenia (unusual bleedings and hemorrhages).

Others: dorsodynia, arthralgia, withdrawal (strengthening of attacks of stenocardia, increase in the ABP).

Frequency of by-effects increases at increase in a dose of drug.

Interaction with other medicines:

At simultaneous use of an atenolol with insulin, peroral hypoglycemic medicines their gipoglikemiziruyushchy action amplifies.

At combined use to anti-hypertensive means of different groups or nitrates there is strengthening of hypotensive action. Simultaneous use of an atenolol and verapamil (or diltiazem) can cause mutual strengthening of cardiodepressive action.

The hypotensive effect is weakened by estrogen (a sodium delay), NPVS, GKS.

At simultaneous use of an atenolol and cardiac glycosides the risk of development of bradycardia and disturbance of AV conductivity increases.

At a concomitant use of an atenolol with Reserpinum, metildopy, a clonidine, verapamil developing of the expressed bradycardia is possible.

Simultaneous in/in administration of verapamil and diltiazem can provoke a cardiac standstill; nifedipine can lead to considerable decrease in the ABP.

At a concomitant use of an atenolol with derivatives of ergotamine, xanthine its efficiency decreases.

At the termination of the combined use of an atenolol and a clonidine treatment by a clonidine is continued by some more days after cancellation of an atenolol.

Simultaneous use with lidocaine can reduce its removal and increase risk of toxic effect of lidocaine.

Use together with derivatives of a fenotiazin promotes increase in concentration of each of drugs in blood serum.

Phenytoinum at in introduction, medicines for the general anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.

At combined use with an Euphyllinum and theophylline perhaps mutual suppression of therapeutic effects.

Simultaneous use with MAO inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of MAO inhibitors and an atenolola has to make not less than 14 days.

The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis. Means for an inhalation anesthesia (derivatives of hydrocarbons) increase risk of oppression of function of a myocardium and development of arterial hypertension.

Amiodaronum increases risk of development of bradycardia and oppression of AV conductivity.

Cimetidinum increases concentration in a blood plasma (slows down metabolism).

Iodinated X-ray contrast medicines for in/in introductions increase risk of development of anaphylactic reactions.

Extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.

Rub - and tetracyclic antidepressants, antipsychotic medicines (neuroleptics), ethanol, sedative and somnolent medicines strengthen oppression of TsNS.

At simultaneous use with insulin and peroral hypoglycemic means masks symptoms of the developing hypoglycemia.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of a peripheral krovobrashcheniye.

Contraindications:

— hypersensitivity to drug;
— cardiogenic shock;
— AV blockade of II and III degrees;
— the expressed bradycardia (ChSS less than 45-50 уд. / min.);
— SSSU;
— sinoauricular block;
— acute or chronic heart failure (in a decompensation stage);
— a cardiomegaly without symptoms of heart failure;
— Printsmetal's stenocardia;
— arterial hypotension (in case of use at a myocardial infarction, systolic the ABP less than 100 mm hg);
— lactation period;
— concomitant use of MAO inhibitors;
— age up to 18 years (efficiency and safety are not established).

With care: diabetes mellitus; metabolic acidosis; hypoglycemia; allergic reactions in the anamnesis; chronic obstructive pulmonary disease (including emphysema of lungs); AV blockade of the I degree; the chronic heart failure (compensated); obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome); pheochromocytoma; liver failure; chronic renal failure; myasthenia; thyrotoxicosis; a depression (including in the anamnesis); psoriasis; pregnancy; advanced age.

Use drug ATENOLOL BELUPO at pregnancy and feeding by a breast
Pregnant women should appoint атенолол only when the advantage for mother exceeds potential risk for a fruit.
In need of use of an atenolol in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination (атенолол it is allocated with breast milk).

Use at abnormal liver functions
With care: liver failure.

Use at renal failures
Correction of the mode of dosing is necessary for patients with disturbances of secretory function of kidneys.

In the presence of a renal failure recommend dose adjustment depending on the clearance of creatinine (CC). Patients with a renal failure at KK values have higher than 35 ml/min. / 1.73м2 (normal values make 100-150 ml/min. / 1.73 sq.m) considerable cumulation of Atenolol Belupo does not occur.

The following maximum doses for patients with a renal failure are recommended:

KK (ml/min. / 1.73 sq.m)	T1/2 of an atenolol (h)	Maximum dose
15-35	16-27	50 mg in days or 100 mg every other day
less than 15	more than 27	50 mg every other day or 100 mg of 1 times in 4 days

Use for elderly patients
With care to apply to patients of advanced age.

Use for children
Drug is contraindicated to children up to 18 years.

Overdose:

Symptoms: the expressed bradycardia, AV blockade of the II-III degree, increase of symptoms of heart failure, excessive decrease in the ABP, breath difficulty, a bronchospasm, dizziness, a syncope, arrhythmia, ventricular premature ventricular contraction, cyanosis of nails of fingers or palms, spasms.

Treatment: a gastric lavage and purpose of the adsorbing medicines; at emergence of a bronchospasm it is shown inhalation or in/in introduction of a beta2-adrenomimetik of salbutamol. At disturbance of AV conductivity, bradycardia - in/in introduction of 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction - lidocaine (drugs 1A of a class are not used); at decrease in the ABP in the patient has to be in the provision of Trendelenburga. If there are no fluid lungs signs - in/in plasma substituting solutions, at inefficiency - introduction of Epinephrinum, dopamine, Dobutaminum; at chronic heart failure - cardiac glycosides, diuretics, a glucagon; at spasms - in/in diazepam. Carrying out dialysis is possible.

Storage conditions:

At a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, покр. film cover, 25 mg: 30 pieces.

Tablets, покр. film cover, 50 mg: 30 pieces.

Tablets, покр. film cover, 100 mg: 14 or 28 pieces.