Aritel Plus - instructions for use, doses, side effects, contraindications

Excipients: pregelatinized starch 17 mg; silicon dioxide colloid (Aerosil) 1.5 mg; lactose monohydrate (sugar milk) 40 mg; magnesium stearate 0.75 mg; microcrystalline cellulose 32 mg;

composition of film shell: Selekoate AQ-02140/A 3 mg, [hypromellose (hydroxypropylmethylcellulose) 1.65 mg, macrogol (polyethylene glycol 400) 0.27 mg, macrogol (polyethylene glycol 6000) 0.42 mg, titanium dioxide 0.63 mg, dye sunset yellow, 0.03 mg].

Description:

The tablets covered with a film cover of yellow-orange color, round, biconcave with crosswise risk. On the cross-section, two layers: the inner layer is almost white.

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

ATX: & nbsp

C.07.B.B.07 Bisoprolol in combination with thiazides

Pharmacodynamics:

Aritel® Plus is a combined preparation that includes bisoprolol and hydrochlorothiazide.

Bisoprolol

Selective β₁-adrenoceptor without internal sympathomimetic activity. Has antihypertensive, antiarrhythmic and antianginal action. It blocks at low doses β₁(adenosine triphosphate (ATP)), reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect , reduces the excitability and contractility of the myocardium). As the dose increases, β blocks2-adrenoceptors.

The total peripheral vascular resistance at the beginning of the use of β-blockers in the first 24 hours increases (as a result of the reciprocal increase in α-adrenergic receptor activity and elimination of β stimulation2-adrenoreceptors), after 1-3 days it returns to the initial, and with a long-term administration decreases.

The hypotensive effect is associated with a decrease in the minute volume of blood, suppression of sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system by inhibiting the β-adrenoreceptors of the juxtaglomerular renal apparatus (which leads to a decrease in renin secretion), restoration of the sensitivity of the aortic arch baroreceptors activity in response to a decrease in blood pressure) and influence on the central nervous system. With arterial hypertension, the effect develops in 2-5 days, stable effect - after 1-2 months.

Hydrochlorothiazide

Thiazide diuretic. Reduces the reabsorption of sodium ions in the cortical segment of the Henle loop, without affecting its area passing through 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. Increases the excretion of magnesium ions by the kidneys; It detains calcium ions in the body and inhibits the excretion of urates.The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, persists for 6-12 hours. The diuretic effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min.

Pharmacokinetics:

Bisoprolol

After ingestion, absorption from the gastrointestinal tract is 80-90%.

Eating does not affect the degree of absorption. The time to reach the maximum concentration in the blood plasma is 2-4 hours. The connection with plasma proteins is about 30%. Poorly penetrates the blood-brain and placental barrier. Secretion of breast milk is insignificant. Metabolised in the liver.

The half-life is 9-12 hours. It is excreted by the kidneys (50% - unchanged), less than 2% - through the intestine.

Hydrochlorothiazide

When ingested, absorbed quickly, but incomplete. The time to reach the maximum concentration in the blood plasma is about 14 hours. Bioavailability of hydrochlorothiazide - 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 by the kidneys mainly unchanged through glomerular filtration and active tubular secretion.The half-life is about 8 hours.

Indications:

Arterial hypertension of mild to moderate severity.

Contraindications:

- Hypersensitivity to bisoprolol and other components of the drug;

- hypersensitivity to hydrochlorothiazide and other sulfonamides;

- bronchial asthma;

- chronic obstructive pulmonary disease;

- Decompensated chronic heart failure (CHF);

- cardiogenic shock;

- syndrome of weakness of the sinus node (including sinoatrial blockade);

- atrioventricular blockade of II and III degree without artificial pacemaker;

- pronounced bradycardia (heart rate less than 50 beats per minute);

- Variable angina pectoris (Prinzmetal angina);

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

- hard-to-control diabetes mellitus;

- severe peripheral circulatory disorders (including Raynaud's syndrome);

- severe arterial hypotension (systolic blood pressure less than 100 mm Hg);

- refractory hypokalemia, hyponatremia, hypercalcemia;

- metabolic acidosis;

- hypovolemia;

- acute renal insufficiency;

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

- simultaneous application with floktaphenin, sultopride;

- simultaneous reception of antiarrhythmic drugs;

- simultaneous reception of lithium preparations;

- simultaneous administration of monoamine oxidase inhibitors (MAO) (with the exception of MAO type B inhibitors);

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

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- pregnancy;

- lactation period.

Carefully:

Conducting desensitizing therapy, atrioventricular blockade of the first degree, psoriasis, ischemic heart disease, hepatic insufficiency, renal failure (QC more than 30 ml / min), thyrotoxicosis, pheochromocytoma (against treatment with α-adrenoblockers), hyperthyroidism, water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia), gout, restrictive cardiomyopathy, congenital heart disease or heart valve flaw with severe hemodynamic disorders, severe diet, depression (including in anamnesis), miast in elderly patients.

Dosing and Administration:

Aritel® Plus is recommended in the morning, during meals. Tablets should be swallowed whole, not liquid, squeezed with a small amount of water. The recommended initial dose is 2.5 mg bisoprolol + 6.25 mg hydrochlorothiazide once a day.

For individual dose selection, Aritel® Plus is available in the following dosages containing:

- 2.5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide

- 5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide

- 10 mg of bisoprolol and 6.25 mg of hydrochlorothiazide

Each subsequent increase in the dose should be carried out at least two weeks later.

If the increase in the dose of the drug is poorly tolerated by the patient, a dose reduction is possible.

Patients with moderate impairment of liver function, moderate impairment of renal function, and also in elderly patients do not need dose adjustment.

In patients with severe impairment of liver and kidney function (creatinine clearance more than 30 ml / min), the maximum daily dose of bisoprolol should not exceed 10 mg.

The duration of the course is set by the doctor.

Side effects:

From the central and peripheral nervous system: increased fatigue, asthenia, anxiety,dizziness, headache, drowsiness or insomnia, depression, memory / attention disorder, fainting, vertigo, sensation of cold and numbness of limbs, convulsions, paresthesia, hypoesthesia, hyperesthesia, hallucinations, nightmares.

From the cardiovascular system: sinus bradycardia, marked decrease in arterial pressure, violation of atrioventricular conduction, ventricular extrasystole, orthostatic hypotension, exacerbation of chronic heart failure, peripheral edema.

From the respiratory system: in predisposed patients, laryngo- and bronchospasm, shortness of breath, rhinitis, sinusitis, pharyngitis, nasal congestion.

From the digestive system: abdominal pain, peptic ulcer, gastritis, dyspepsia, dryness of the oral mucosa, nausea, vomiting, diarrhea, constipation, hepatitis, jaundice.

From the musculoskeletal system: muscle weakness, spasms of the calf muscles, arthralgia, including pain in the chest, back, neck, intermittent claudication.

From the sense organs: visual impairment, hearing impairment, decreased lacrimal gland production (patients,using contact lenses), dryness and soreness of the eyes, conjunctivitis.

From the genitourinary system: violation of potency / libido, cystitis, renal colic, polyuria, interstitial nephritis.

From the endocrine system: hyperglycemia (in patients with insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin).

Allergic reactions: skin rash, hives, purpura, photosensitivity, anaphylaxis.

From the skin: rashes, acne, itchy skin, increased sweating, skin hyperemia, exfoliative dermatitis, exacerbation of psoriasis symptoms, alopecia.

Laboratory indicators: increased activity of "liver" transaminases, hypertriglyceridemia, hypercholesterolemia, hyperglycemia, glucosuria, hyperuricemia, reversible increase in the concentration of creatinine and urea in the blood plasma, water-electrolyte balance disorders, metabolic alkalosis, thrombocytopenia, leukopenia, agranulocytosis.

Influence on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: gout, withdrawal syndrome (hypertension), weight gain.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, acute heart failure, ventricular extrasystole, atrioventricular block, convulsions, bronchospasm.

Treatment: gastric lavage, the appointment of absorbents, symptomatic therapy.

In the case of a pronounced decrease in blood pressure, it is necessary to give the patient a horizontal position with elevated legs, to replenish the volume of circulating blood.

When bradycardia is intravenously administered atropine in a dose of 1-2 mg, glucagon in a dose of 12 mg (slowly bolus), if necessary - as an infusion at a dose of 1-10 mg / hour.

In the subsequent it is appointed epinephrine (epinephrine) at a dose of 15-85 μg (the administration of which can be repeated, but its total amount should not exceed 300 μg) or dopamine in a dose of 2.5-10 μg / kg / min.

In acute heart failure, cardiac glycosides, diuretics, glucagon. If there are no signs of pulmonary edema, then intravenously administered plasma-substituting solutions, if they are ineffective - epinephrine, dopamine, dobutamine.

When ventricular extrasystole is used lidocaine.

With the development of atrioventricular block, intravenous 1-2 mg of atropine, epinephrine, or a temporary pacemaker should be administered.

When convulsions are recommended diazepam intravenously.

In bronchospasm, β₂-adrenomimetics.

Interaction:

With the simultaneous use of the drug Aritel® Plus with phenytoin (with intravenous administration) and drugs for inhalation of general anesthesia (derivatives of hydrocarbons), the cardiopepressive effect and the likelihood of excessive reduction in blood pressure (due to the content of bisoprolol) may increase.

The clearance of lidocaine and xanthine may decrease due to a possible increase in their concentrations in the blood plasma, especially in patients with initially elevated clearance of theophylline (due to the content of bisoprolol in the formulation).

With the simultaneous use of calcium and / or vitamin preparations D in high doses, hypercalcemia may develop and the risk of metabolic acidosis (due to the content of the drug hydrochlorothiazide) increases.

Aritel® Plus is contraindicated for use in combination with floktaphenin, sultopride, MAO inhibitors (with the exception of MAO type B inhibitors). It is possible to strengthen the antihypertensive effect of the drug Aritel® Plus with simultaneous use with antidepressants, antipsychotics,blockers "slow" calcium channel (BCCI) (amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), inhibitors of angiotensin converting enzyme (including captopril, enalapril), irbesartan, diuretic, clonidine, sympatholytic, hydralazine, and other antihypertensive agents.

It is possible to weaken the hypotensive effect of the drug Aritel®. Plus with simultaneous administration with glucocorticosteroids (for systemic use), estrogens, nonsteroidal anti-inflammatory drugs (indomethacin, piroxicam, naproxen, phenylbutazone) and tetracosactide.

With simultaneous use with the drug Aritel® Plus, the effects of nondepolarizing muscle relaxants and the anticoagulant effect of coumarin derivatives may be enhanced Cardiac glycosides, methyldopa, reserpine, guanfacine, BCCC (verapamil, diltiazem, amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), antiarrhythmics, as well as agents that can initiate arrhythmias such as pirouettes (astemizole, beprideil, erythromycin, halofantrine, pentamidine, sparfloxacin, terfenadine), increase the risk of developing and / or strengthening bradycardia, atrioventricular blockade and chronic heart failure. With simultaneous application with sotalol hypokalemia and development of ventricular arrhythmia such as "pirouette" is possible. With the simultaneous use of the drug Aritel® Plus with lithium salts, it is possible to increase the concentration of the latter in the blood to a toxic level.

The effectiveness of insulin and hypoglycemic agents for oral administration may be reduced. Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

With the simultaneous use of the preparation Aritel® Plus with allergens used for immunotherapy, or with allergen extracts for skin tests, as well as with allopurinol or with iodine-containing radiopaque diagnostic agents for intravenous administration, the risk of allergic reactions increases.

With the simultaneous administration of the drug Aritel® Plus with mefloquine, bradycardia may develop; with carbamazepine - hyponatremia; with cyclosporine - an increase in serum creatinine is possible.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma; rifampicin - shortens the half-life of bisoprolol.

Bisoprolol and hydrochlorothiazide should not be combined with other drugs from the group of β-blockers.

Special instructions:

During the therapy with Arilit® Plus, heart and heart rate control is necessary (at the beginning of treatment, every day, then every 3-4 months), and for glucose in the blood of patients with diabetes mellitus (once every 4-5 months). In elderly patients, therapy should begin with a dosage form of the drug containing a low dose of bisoprolol. In this case, regular monitoring of the patients' condition is necessary, it is also recommended to monitor the kidney function (once every 4-5 months). It is necessary to teach the patient how to calculate heart rate. In the period of therapy with the drug Aritel® Plus, it is also necessary to monitor the parameters of the acid-base state and the level of electrolytes (potassium, sodium, calcium).

It is necessary to reduce the dose of the drug Aritel® Plus (by reducing the content of bisoprolol), if the heart rate at rest does not exceed 50-55 beats per minute.

In the period of therapy with the drug Aritel® Plus, it is also necessary to monitor the parameters of the acid-base state and the level of electrolytes (potassium, sodium, calcium).

Bisoprolol: discontinue treatment should be gradual, especially in coronary heart disease (concomitant CHD). The dose is reduced within two weeks. If necessary, conduct appropriate therapy to prevent attacks of angina pectoris.

In bronchial asthma and chronic obstructive pulmonary disease (COPD), treatment starts with a minimal dose. Preliminary exercise of functional respiratory tests. With the development of bronchospasm, β-adrenomimetics are prescribed.

In chronic heart failure (concomitant CHF) treatment is carried out under the supervision of a doctor, in minimum doses.

Given the negative dromotropic effect of β-blockers, they should be administered with caution to patients with AV blockade of the I st.

In patients with peripheral circulatory disorders (Raynaud's disease), β-adrenoblockers can cause an exacerbation of the course of the disease, so the drug is contraindicated in such patients (see "Contraindications").

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

Patients with pheochromocytoma should not be prescribed a drug until treatment with α-blockers is performed. During the treatment, blood pressure control (BP) is necessary.

It is recommended to stop therapy with Arilit® Plus in the development of depression caused by the adrenoblocker (due to the content of bisoprolol in it).

In elderly patients, treatment starts with a low dose, under the control of the patient's condition.

Patients with concomitant diabetes should be aware of the possibility of hypoglycemia and the need for regular monitoring of blood glucose (especially in the case of hypokalemia). Bisoprolol can mask signs of hypoglycemia (tachycardia, palpitations, sweating).

Patients who use contact lenses should be careful when using Arilit® Plus, since β-adreno-blockers can reduce the production of the lacrimal gland.

Therapy with β-blockers can aggravate the course of psoriasis.

In patients who had a history of anaphylactic reactions (especially flockafenin or desensitizing drugs), treatment with β-blockers can exacerbate these reactions and lead to the development of resistance to epinephrine in usual doses.

Athletes should be informed that this drug can give false positive results in doping tests.

Hydrochlorothiazide: it is necessary to control sodium in the blood (especially in the elderly and with cirrhosis of the liver). It is necessary to monitor the concentration of potassium in the blood in elderly patients, with simultaneous treatment with thiazide and thiazide-like diuretics, with cirrhosis accompanied by edema, ascites, with coronary artery disease or CHF, with an elongated interval Q-T. Hypokalemia increases the risk of arrhythmias, increases the toxicity of cardiac glycosides. The first determination of the concentration of potassium in the blood should be done during the first week of treatment.

Thiazide diuretics can reduce the excretion of calcium in the urine, which leads to temporary hypercalcemia. Temporary hypercalcemia may be associated with undiagnosed hyperparathyroidism. Before the study of parathyroid function, treatment with thiazides should be discontinued.

In patients with hyperuricemia, the risk of developing gout attacks is increased (the dose is selected individually under the control of the level of uric acid in the blood serum).Before the study of the function of parathyroid glands, treatment with the drug Aritel® Plus should be discontinued, as against the background of its reception, transient hypercalcemia may occur.

Thiazide diuretics are effective at normal or slightly reduced (creatinine concentration less than 25 mg / ml or 220 μmol / L) of kidney function.

Hypovolemia leads to a decrease in glomerular filtration, which leads to an increase in urea and creatinine in the blood in patients with normal renal function. Patients with chronic renal failure may have an increase in existing disorders.

Form release / dosage:Tablets, film-coated, 2.5 mg + 6.25 mg.

Packaging:

(10) - a contour mesh package (1) / 1 contour pack together with the instruction for use is placed in a pack of cardboard / - a cardboard package
(10) - a contour cell package (10) / 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard / - a cardboard package
(10) - a contour mesh package (2) / 2 contour packagings together with the instruction for use are placed in a pack of cardboard / - a cardboard package
(10) - a contour mesh package (3) / 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard / - a cardboard package
(10) - a contour mesh package (5) / 5 contour mesh packages together with the instructions for use are placed in a pack of cardboard / - a cardboard package
(30) - a contour mesh package (1) / 1 contour pack together with the instruction for use is placed in a pack of cardboard / - a cardboard package
(30) - a contour mesh package (3) / 3 contour packagings together with the instruction for use are placed in a pack of cardboard / - a cardboard package
(7) - a contour mesh package (1) / 1 contour pack together with the instruction for use is placed in a pack of cardboard / - a cardboard package
(7) - a contour mesh package (2) / 2 contour mesh packages together with the instruction for use are placed in a pack of cardboard / - a pack of cardboard
(7) - contour pack (4) / 4 contour packs together with instructions for use are placed in a pack of cardboard / - cardboard pack

Storage conditions:In a dry, dark place, at a temperature of no higher than 25 FROM.

Keep out of the reach of children.

Shelf life:2 years.

Terms of leave from pharmacies:On prescription

Registration number:LP-000649

Date of registration:28.09.2011

Date of cancellation:2016-09-28

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp27.11.2015

Illustrated instructions

Instructions

Aritel® Plus (Arital® Plus)