Арител®

General characteristics. Structure:

Active agent: bisoprolola of a fumarat of 5 or 10 mg

Excipients: potato starch, povidone (kollidon-30), lactose, cellulose microcrystallic, silicon dioxide colloid, magnesium stearate, gipromelloz, macrogoal (polyethyleneglycol 400, 4000), titanium dioxide, talc, ferrous oxide yellow, ferrous oxide red

Description
Tablets, film coated light-orange color round, biconvex form. On cross section two layers are visible.

Pharmacological properties:

The selection beta1 — adrenoblocker, without own sympathomimetic activity, has no clinically significant membrane stabilizing properties. Reduces activity of a renin of plasma, reduces the need of a myocardium for oxygen, reduces the heart rate (HR) (at rest and at loading). Has hypotensive, antiarrhytmic and anti-anginal effect. Blocking in low doses beta1 — heart adrenoceptors, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action, oppresses conductivity and excitability, reduces contractility of a myocardium.

The general peripheric vascular resistance at the beginning of drug use, in the first 24 h, increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation beta2-adrenoceptors) which in 1–3 days is returned to initial, and at long appointment decreases.

The hypotensive effect is connected with reduction of minute volume of blood, sympathetic stimulation of peripheral vessels, decrease of the activity a system renin-angiotenzinovoy (is of great importance for patients with initial hypersecretion of a renin), recovery of sensitivity in response to a lowering of arterial pressure (ABP) and influence on the central nervous system (CNS). At arterial hypertension the effect occurs in 2–5 days, stable action — in 1–2 months.

The anti-anginal effect is caused by reduction of need of a myocardium for oxygen as a result of an urezheniye of heart rate and decrease in contractility, lengthening of a diastole, improvement of perfusion of a myocardium. 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.

The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of atrioventricular (AV) carrying out (it is preferential in antegrade and, to a lesser extent, in retrograde the directions through an AV node) and on additional ways.

At use in average therapeutic doses, unlike non-selective beta adrenoblockers, exerts less expressed impact on the bodies containing beta2-adrenoceptors (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism, does not cause a delay of ions of sodium (Na+) in an organism; expressiveness of atherogenous action does not differ from effect of propranolol. At use in high doses (200 mg and more) the blocking effect renders on both subtypes of beta adrenoceptors, mainly, in bronchial tubes and unstriated muscles of vessels.

Pharmacokinetics. Absorption — 80 — 90%, meal does not influence absorption. The maximum concentration in a blood plasma is observed in 1–3 h, communication with proteins of a blood plasma about 30%. Permeability through a blood-brain barrier and a placental barrier - low, secretion with breast milk — low.
The elimination half-life of 10 - 12 hours is metabolized in a liver. It is removed by kidneys — 50% in an invariable look, less than 2% with bile.

Indications to use:

- chronic heart failure (CHF);
- arterial hypertension;
- coronary heart disease: prevention of attacks of stable stenocardia.

Route of administration and doses:

Inside, in the morning on an empty stomach, without chewing, 5 mg once. If necessary the dose is increased to 10 mg of 1 times a day. The maximum daily dose — 20 mg/days.
Patients with a renal failure at clearance of creatine have less than 20 ml/min. or with the expressed abnormal liver functions the maximum daily dose — 10 mg.

Features of use:

Control of the patients accepting Aritel® has to include measurement of ChSS and the ABP (in an initiation of treatment — daily, then 1 time in 3–4 months), carrying out an ECG, blood glucose definition 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.

Before an initiation of treatment it is recommended to conduct a research of function of external respiration at patients with the burdened bronchopulmonary anamnesis.

Approximately at 20% of patients with stenocardia beta adrenoblockers are inefficient. The main reasons — heavy coronary atherosclerosis with a low threshold of ischemia (ChSS less

100 уд. / min.) and the increased final diastolic volume of a left ventricle breaking a subendocardial blood stream.

At "smokers" efficiency of beta adrenoblockers is lower.

The patients using contact lenses have to consider that against the background of treatment reduction of products of the lacrimal liquid is possible.

When using patients with a pheochromocytoma have a risk of development of paradoxical arterial hypertension (if it is previously not reached effective alpha адреноблокада).

At a thyrotoxicosis of Aritel® can disguise 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 concentration of glucose in blood to normal level does not detain.

At a concomitant use of a clonidine its reception can be stopped only in several days after Aritel's cancellation ®.

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.

In case of need performing planned surgical treatment carry out drug withdrawal for 48 h prior to the beginning of the general anesthesia. If the patient accepted drug before operation, it should pick up medicine for the general anesthesia with minimum negative inotropic effect.

Reciprocal activation of a vagus nerve can be eliminated with intravenous administration of atropine (1–2 mg).

The medicines reducing stocks of catecholamines (including, 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.

Patients with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines. The overdose is dangerous by development of a bronchospasm.

In case of identification at patients of advanced age of the accruing bradycardia (less than 50 уд. / min.), the expressed decrease in the ABP (systolic the ABP is lower than 100 mm hg), AV of blockade, it is necessary to reduce a dose or to stop treatment.

It is recommended to stop therapy at development of a depression.

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 within 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 vanilinmindalny acid; credits of antinuclear antibodies.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the central nervous system: increased fatigue, weakness, dizziness, a headache, frustration of a dream, a depression, concern, confusion of consciousness or short-term loss of memory, a hallucination, an adynamy, a myasthenia, paresthesias in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), a tremor.

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

From cardiovascular system: a sinus bradycardia, heartbeat, disturbance of conductivity of a myocardium, AV blockade (up to development of total cross block and a cardiac standstill), arrhythmias, easing of contractility of a myocardium, development (aggravation) of chronic heart failure (puffiness of anklebones, feet; asthma), decrease in the ABP, orthostatic hypotension, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, cold snap of the lower extremities, Reynaud's syndrome), stethalgia.

From the alimentary system: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain, locks or diarrhea, abnormal liver functions (dark urine, yellowness of scleras or skin, cholestasia), taste changes.

From respiratory system: a nose congestion, difficulty of breath at appointment in high doses (selectivity loss) and/or at predisposed patients — laringo-and a bronchospasm.

From endocrine system: a hyperglycemia (at patients with an insulinonezavisimy diabetes mellitus), a hypoglycemia (at the patients receiving insulin), a hypothyroid state.

Allergic reactions: skin itch, rash, small tortoiseshell.

From integuments: sweating strengthening, dermahemia, dieback, psoriazopodobny skin reactions, aggravation of symptoms of psoriasis.

Laboratory indicators: thrombocytopenia (unusual bleedings and hemorrhages), agranulocytosis, leukopenia, change of activity of enzymes of a liver (increase in ALT, nuclear heating plant), level of bilirubin, triglycerides.

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

Others: dorsodynia, arthralgia, weakening of a libido, decrease in a potentiality, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP).

Interaction with other medicines:

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 at the patients receiving бисопролол.

Yodosoderzhashchy X-ray contrast medicines for intravenous administration increase risk of development anaphylactic reactions.

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

Changes efficiency of insulin and peroral hypoglycemic medicines, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP). Reduces clearance of lidocaine and xanthines (except Diphyllinum) and increases their concentration in plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.

Hypotensive effect non-steroidal anti-inflammatory drugs (Na delay + and prostaglandin synthesis blockade by kidneys) weaken, glucocorticosteroids and estrogen (a delay of ions of Na+).

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of "slow" calcium channels (verapamil, diltiazem), Amiodaronum and other antiarrhytmic medicines increase risk of development or aggravation of bradycardia, AV of blockade, a cardiac standstill and heart failure.

Nifedipine can lead to considerable decrease in the ABP.

Diuretics, clonidine, sympatholytics, гидралазин and other hypotensive medicines can lead to excessive decrease in the ABP.

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.

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 a bisoprolola has to make not less than 14 days.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.

Ergotamine increases risk of development of disturbance of peripheric circulation; Sulfasalazinum increases concentration of a bisoprolol in plasma; rifampicin shortens an elimination half-life.

Contraindications:

Hypersensitivity to components of drug and other beta adrenoblockers, shock (including cardiogenic), a collapse, a fluid lungs, acute cordial insufficiency, chronic heart failure in a stage of a decompensation, AV blockade of the II-III Art., sinuatrial blockade, a sick sinus syndrome, the expressed bradycardia, Printsmetal's stenocardia, a cardiomegaly (without symptoms of heart failure), arterial hypotension (systolic the ABP less than 100 mm rt.st., especially at a myocardial infarction); bronchial asthma and a chronic obstructive pulmonary disease in the anamnesis; a concomitant use of inhibitors of a monoaminooxidase (MAO) (except for MAO-B), late stages of disturbance of peripheric circulation, a Raynaud's disease), a pheochromocytoma (without simultaneous use of alpha adrenoblockers), a metabolic acidosis, age up to 18 years (efficiency and safety are not established).

With care: a liver failure, a chronic renal failure, a myasthenia, a thyrotoxicosis, a diabetes mellitus, an atrioventricular block of the I degree, a depression (including in the anamnesis), psoriasis, advanced age.

Use at pregnancy and in the period of a lactation perhaps if the advantage for mother exceeds risk of development of side effects in a fruit and the child.

Overdose:

Symptoms: arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, AV blockade, the expressed decrease in the ABP, chronic heart failure, cyanosis of nails of fingers or palms, breath difficulty, a bronchospasm, dizziness, unconscious states, spasms.

Treatment: a gastric lavage and purpose of the adsorbing medicines; symptomatic therapy: at the developed AV to blockade - intravenous (in/in) 1–2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction — lidocaine (the drugs Ia of a class are not used); at decrease in the ABP — the patient has to be in the provision of Trendelenburga; if there are no fluid lungs signs — intravenously plasma substituting solutions, at inefficiency — introduction of Epinephrinum, dopamine, Dobutaminum (for maintenance of chronotropic and inotropic action and elimination of the expressed decrease in the ABP); at heart failure — cardiac glycosides, diuretics, a glucagon; at spasms — intravenously diazepam; at a bronchospasm — beta2 — adrenostimulyator it is inhalation.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. In the place, unavailable to children. Period of validity 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 5 mg, 10 mg.
On 10, 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 3, 5, 10 blister strip packagings on 10 tablets or 1 blister strip packaging on 30 tablets with the application instruction in a pack from a cardboard.