Арител® Plus

General characteristics. Structure:

Active agents for a dosage of 5 mg + 6,25 mg — a bisoprolola of a fumarat (a bisoprolol of a gemifumarat) of 5 mg and a hydrochlorothiazide of 6,25 mg;

active agents for a dosage of 10 mg +6,25 mg — a bisoprolol of a fumarat (a bisoprolol of a gemifumarat) of 10 mg and a hydrochlorothiazide of 6,25 mg;

excipients — silicon dioxide colloid (aerosil), starch corn (C*Pharm 93000 starch), lactose (sugar milk), magnesium stearate, cellulose microcrystallic;

structure of a film cover — Selekout of AQ-02140 [a gipromelloz (gidroksipropilmetiltsellyuloz), a macrogoal (polyethyleneglycol 400), a macrogoal (polyethyleneglycol 6000), titanium dioxide, dye a sunset yellow].

Description: Tablets, film coated yellow-orange color, round, biconvex. On cross section two layers: cover

yellow-orange color, kernel of white color.

Pharmacological properties:

Pharmacodynamics. Арител® Plus is the combined means which part are бисопролол and a hydrochlorothiazide.

Bisoprolol — the selection beta1-adrenoblocker without internal sympathomimetic activity. Has hypotensive, antiarrhytmic and anti-anginal effect. Blocking heart beta1-adrenoceptors in low doses, reduces stimulated catecholamines formation of cyclic adenosinemonophosphate (tsAMF) from adenosinetriphosphate (ATP), reduces intracellular current of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat the heart rate (HR), oppresses cordial conductivity, reduces excitability and contractility of a myocardium). At increase in a dose blocks beta2-adrenoceptors.

The general peripheric vascular resistance at the beginning of use of beta adrenoblockers, in the first 24 h increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors), 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, suppression of sympathetic stimulation of peripheral vessels, decrease of the activity system renin-angiotensin-aldosteronovoy by inhibition of beta adrenoceptors of the juxtaglomerular device of kidneys (that leads to reduction of secretion of a renin), recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to a lowering of arterial pressure) and influence on the central nervous system. At arterial hypertension the effect develops in 2–5 days, stable action — in 1–2 months.

Hydrochlorothiazide — thiazide diuretic. Reduces a reabsorption of ions of sodium in a cortical segment of a Henle's loop, without influencing its site passing in a kidney medulla. Blocks a karboangidraza in proximal department of gyrose renal tubules, strengthens removal by kidneys of potassium ions, hydrocarbonates and phosphates. Practically does not influence an acid-base state. Strengthens removal by kidneys of ions of magnesium; detains in an organism calcium ions and slows down removal of urates. The diuretic effect develops in 1–2 h, reaches a maximum in 4 h, remains during 6–12 h. Diuretic action decreases at reduction in the rate of glomerular filtering and stops at the size of its less than 30 ml/min.

Pharmacokinetics. Bisoprolol

After intake absorption makes 80–90% of digestive tract. Meal does not influence extent of absorption. Time of achievement of the maximum concentration in a blood plasma makes 2–4 h. Communication with proteins of a blood plasma makes about 30%.

Badly gets through a blood-brain and placental barrier. Secretion with breast milk — insignificant. It is metabolized in a liver.

The elimination half-life makes 9–12 h. It is removed by kidneys (50% — in not changed look), less than 2% — through intestines.

Hydrochlorothiazide

At intake it is soaked up quickly, but it is incomplete. Time of achievement of the maximum concentration in a blood plasma makes about 4 h. Bioavailability of a hydrochlorothiazide — 60 - 80%. Communication with proteins of a blood plasma makes 40%.

Gets through a placental barrier, and it is allocated in breast milk. It is not metabolized. It is removed by kidneys generally in not changed look by means of glomerular filtering and active canalicular secretion. The elimination half-life makes about 8 h.

Indications to use:

Arterial hypertension of soft and moderate severity.

Route of administration and doses:

Арител® Plus is recommended to be accepted in the morning (during meal). Tablets should be swallowed entirely, without chewing, washing down with a small amount of liquid, 1 time a day.

The dose of drug should be selected individually.

In an initiation of treatment it is necessary to accept on 1 tablet of the drug Aritel® Plus containing 5 mg bisoprolola/6,25 mg of a hydrochlorothiazide of 1 times/days. At insufficient expressiveness of therapeutic effect in 2 weeks the dose can be increased, accepting on 1 tablet of the drug Aritel® Plus containing 10 mg bisoprolola/6,25 mg of a hydrochlorothiazide, 1 times/days.

The patient with abnormal liver functions, and also correction of the mode of dosing is not required to patients of advanced age.

At patients with heavy abnormal liver functions and kidneys (KK more than 30 ml/min.) the maximum daily dose of a bisoprolol should not exceed 10 mg.

Features of use:

During therapy by the drug Aritel® Plus control of ChSS and the ABP (in an initiation of treatment — daily, then — 1 time in 3–4 months), behind the content of glucose in blood at patients with a diabetes mellitus is necessary (1 time in 4–5 months). At elderly patients it is recommended to control function of kidneys (1 times in 4–5 months). It is necessary to train the patient in a technique of calculation of ChSS. It is necessary to reduce doses of the drug Aritel® Plus (due to reduction of maintenance of a bisoprolol in it) from 10 to 5 mg if ChSS at rest does not exceed 50–55 beats/min.

During therapy by the drug Aritel® Plus it is also necessary to control indicators of an acid-base state and level of electrolytes (potassium, sodium, calcium).

At patients it is necessary to be careful with disturbances of peripheric circulation at purpose of the drug Aritel® Plus.

At a thyrotoxicosis of Aritel® Plus (due to the maintenance of a bisoprolol in it) can mask clinical signs of a disease (for example, tachycardia).

Patients with a pheochromocytoma should not appoint Aritel® Plus until treatment is appointed alpha adrenoblockers. At the same time it is necessary to control the ABP. It is recommended to stop therapy by the drug Aritel® Plus at development of the depression caused by reception

beta adrenoblocker (due to maintenance of a bisoprolol in it).

At patients of advanced age treatment by the drug Aritel® Plus should be begun with the dosage form of drug containing a low dose of a bisoprolol (5 mg). At the same time regular control of a condition of patients is necessary.

The special attention is required in cases of carrying out surgical intervention under the general anesthesia at the patients accepting beta adrenoblockers. Such patients should cancel Aritel® Plus in 48 hours prior to an operative measure, to warn the anesthesiologist that the patient accepts the means drug Aritel® Plus as for the general anesthesia it is necessary to choose drug with the minimum negative inotropic effect.

Against the background of therapy by beta adrenoblockers the aggravation of a course of psoriasis is possible. Patients with this disease of Aritel® should appoint Plus with care.

At instructions in the anamnesis on anaphylactic reactions, irrespective of the reason of their emergence, especially when performing the desensibilizing therapy, treatment by the drug Aritel® Plus (due to the maintenance of a bisoprolol in it) can increase risk of emergence of allergic reactions and promote development of resistance to treatment by Epinephrinum (adrenaline) in usual doses.

The patients using contact lenses should be careful at use of the drug Aritel® Plus as

beta adrenoblockers can reduce products of the lacrimal liquid.

At patients with a hyperuricemia the risk of development of attacks of an exacerbation of gout is increased. In this case the dose of the drug Aritel® Plus should be selected individually under control of level of uric acid in blood serum. Before a research of function of epithelial bodies treatment by the drug Aritel® Plus needs to be stopped as against the background of its reception there can be a tranzitorny hypercalcemia.

Athletes should be informed that Aritel® contains Plus бисопролол which can yield false positive results when carrying out a drug test.

Influence on ability to driving of motor transport and to control of mechanisms: Арител® Plus should be applied with care at control of vehicles and mechanisms in connection with a possibility of development of dizziness.

Side effects:

From the central and peripheral nervous system: dizziness, headache, adynamy, sleep disorders, depression; increased fatigue, hallucinations, "dreadful" dreams, spasms; cold sense and numbness in extremities.

From cardiovascular system: bradycardia, orthostatic hypotension, disturbance of atrioventricular conductivity, ventricular premature ventricular contraction, aggravation of a course of chronic heart failure.

From respiratory system: a bronchospasm (at predisposed patients).

From the alimentary system: nausea, vomiting, diarrhea, lock, dryness of a mucous membrane of an oral cavity; hepatitis.

From a musculoskeletal system: muscular weakness, systremmas, arthralgia.

From sense bodys: a hearing disorder, decrease in products of the lacrimal glands (it is necessary to consider to the patients using contact lenses), a vision disorder.

From reproductive system: disturbances of a potentiality it is (very rare).

From system of a hemopoiesis: leukopenia, thrombocytopenia.

Allergic reactions: skin itch, rash, erubescence of the person, allergic rhinitis.

From integuments: the increased perspiration, an alopecia, an exacerbation of psoriasis.

From laboratory indicators: increase in activity of "hepatic" transaminases, a gipertriglitseridemiya, a hypercholesterolemia, a hyperglycemia, a glucosuria, a hyperuricemia, reversible increase in content of creatinine and urea in a blood plasma.

Interaction with other medicines:

At simultaneous use of the drug Aritel® Plus with Phenytoinum (at intravenous administration) and medicines for inhalation general anesthesia (derivatives of hydrocarbons) expressiveness of cardiodepressive action and probability of excessive decrease in the ABP can amplify (due to maintenance as a part of drug of a bisoprolol).

The clearance of lidocaine and xanthines can decrease in connection with possible increase in their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline (due to maintenance as a part of drug of a bisoprolol).

At simultaneous use of drugs of calcium and/or vitamin D in high doses the hypercalcemia can develop and the risk of emergence of a metabolic acidosis increases (due to maintenance as a part of hydrochlorothiazide drug).

Арител® Plus is contraindicated to use in a combination with floktafeniny, sultopridy, MAO inhibitors (except for MAO inhibitors of V type).

Strengthening of hypotensive effect of the drug Aritel® Plus at simultaneous use with antidepressants, neuroleptics, blockers of "slow" calcium channels (BMKK) (amlodipiny, felodipiny, nifedipine, nikardipiny, nimodipiny, nitrendipiny), angiotensin-converting enzyme inhibitors (including captopril, enalapril), irbesartany, diuretics, a clonidine, sympatholytics, gidralaziny and other antihypertensives is possible.

Weakening of hypotensive effect of the drug Aritel® Plus at co-administration with glucocorticosteroids (for system use), estrogen, non-steroidal anti-inflammatory drugs (indometacin, piroxicam, Naproxenum, phenylbutazone) and tetrakozaktidy is possible.

At simultaneous use with the drug Aritel® Plus action of not depolarizing muscle relaxants and anticoagulating effect of coumarinic derivatives can amplify. Cardiac glycosides, Methyldopum, Reserpinum, гуанфацин, BMKK (verapamil, diltiazem, амлодипин, фелодипин, nifedipine, никардипин, нимодипин, нитрендипин), antiarrhytmic means, and also means which can initiate arrhythmias like "pirouette" (астемизол, bepridit, erythromycin, галофантрин, pentamidine, спарфлоксацин, терфенадин), increase risk of development and/or strengthening of bradycardia, an atrioventricular block and chronic heart failure. At simultaneous use with sotaloly the hypopotassemia and development of ventricular arrhythmia like "pirouette" is possible.

At simultaneous use of the drug Aritel® Plus with salts of lithium increase in concentration of the last in blood to toxic level is possible.

Efficiency of insulin and hypoglycemic means for intake can decrease.

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

At simultaneous use of the drug Aritel® Plus with the allergens used for an immunotherapy or with extracts of allergens for skin tests, and also with Allopyrinolum or with yodosoderzhashchy X-ray contrast diagnostic intravenous agents, the risk of development of allergic reactions increases.

At co-administration of the drug Aritel® Plus with meflokhiny development of bradycardia is possible; with carbamazepine — hyponatremias; with cyclosporine — increase in content of creatinine in blood serum is possible.

Sulfasalazinum increases concentration of a bisoprolol in a blood plasma; rifampicin — shortens an elimination half-life of a bisoprolol.

Contraindications:

Hypersensitivity to a bisoprolol and other components of drug;
hypersensitivity to a hydrochlorothiazide and other sulfonamides.
bronchial asthma;
chronic obstructive pulmonary disease;
cardiogenic shock;
sick sinus syndrome (including sinuatrial blockade);
atrioventricular block of II and III degrees without artificial pacemaker;
the expressed bradycardia (ChSS less than 50 уд. / min.);
alternative stenocardia (Printsmetal's stenocardia);
pheochromocytoma (without simultaneous use of alpha adrenoblockers);
unmanageable diabetes mellitus;
late stages of disturbance of peripheric circulation (including Reynaud's syndrome);
the expressed arterial hypotension;
refractory hypopotassemia, hyponatremia, hypercalcemia;
metabolic acidosis;
hypovolemia;
acute renal failure;
chronic renal failure (clearance of creatinine (CC) less than 30 ml/min.);
simultaneous use with floktafeniny, sultopridy.
concomitant use of inhibitors of a monoaminooxidase (MAO) (except for MAO inhibitors of V type);
age up to 18 years (efficiency and safety are not established).
lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption;
pregnancy;
lactation period.

With care it is necessary to apply at an atrioventricular block of the I degree, coronary heart disease, liver failure, renal failure (KK more than 30 ml/min.); a thyrotoxicosis, a pheochromocytoma (against the background of treatment by alpha adrenoblockers), water and electrolytic disturbances (a hyponatremia, a hypopotassemia, a hypercalcemia); depressions (including in the anamnesis), a myasthenia, gout, psoriasis, and also at patients of advanced age.

Overdose:

Symptoms: the expressed decrease in the ABP, bradycardia, an acute heart failure, ventricular premature ventricular contraction, an atrioventricular block, spasms, a bronchospasm.

Treatment: a gastric lavage, purpose of the adsorbing means, symptomatic therapy. In case of the expressed decrease in the ABP it is necessary to give to the patient horizontal position with the raised legs, to make completion of volume of the circulating blood. At bradycardia atropine in a dose of 1-2 mg, a glucagon in a dose of 1 mg (slowly bolyusno), if necessary — in the form of infusion in a dose of 1-10 mg/h is intravenously entered. In the subsequent Epinephrinum (adrenaline) in a dose of 15-85 mkg (which introduction can be repeated, but its total quantity should not exceed 300 mkg) or a dopamine in a dose is appointed

2,5–10 mkg/kg/min. At an acute heart failure cardiac glycosides, diuretics, a glucagon are shown. If there are no fluid lungs signs, then plasma substituting solutions are intravenously appointed, at their inefficiency — Epinephrinum, a dopamine, Dobutaminum. At ventricular premature ventricular contraction lidocaine is applied. At the developed atrioventricular block it is necessary to enter intravenously 1–2 mg of atropine, Epinephrinum or to establish a temporary pacemaker. At spasms diazepam intravenously is recommended. At a bronchospasm it is inhalation beta2-adrenomimetik are entered.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 5 mg +6,25 mg and 10 mg +6,25 mg.

On 10, 15 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 1, 3, 6 blister strip packagings on 10 tablets or on 2, 4 blister strip packagings on 15 tablets, or on 1, 2 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.