Instruction for use: Arital Plus

Active substance Bisoprolol + Hydrochlorothiazide

ATX Code C07BB07 bisoprolol in combination with thiazide

Pharmacotherapeutic group:

Hypotensive combined tool (beta1-selective blocker + thiazide diuretic) [Beta-blockers in combination]

The nosological classification (ICD-10)

I10 Essential (primary) hypertension

Hypertension, Arterial hypertension, Arterial hypertension crisis course, Essential Hypertension

Primary hypertension, Arterial hypertension, complications of diabetes, hypertension, The sudden increase in blood pressure, Hypertensive disorders of blood circulation, hypertensive condition, hypertensive crises, hypertension, arterial Hypertension, malignant Hypertension, Hypertonic disease, Hypertensive crisis, Hypertension, accelerated hypertension, malignant hypertension, The aggravation of hypertensive disease, Transient hypertension, Isolated systolic hypertension

I15 Secondary hypertension

Arterial hypertension, complications of diabetes, hypertension, The sudden rise in blood pressure, Hypertensive disorders of blood circulation, hypertensive condition, hypertensive crises, hypertension, arterial hypertension, malignant hypertension, Hypertensive crisis, Hypertension, accelerated hypertension, malignant hypertension, hypertensive crisis, The aggravation of hypertensive disease, Transient hypertension, hypertension, Arterial hypertension, Arterial hypertension crisis course, renovascular hypertension, symptomatic hypertension, renal hypertension, Renovascular hypertension, Symptomatic hypertension

Structure and Composition

Tablets, film-coated Table 1.

active substance:

bisoprolol fumarate (bisoprolol hemifumarate) 2.5 mg

6.25 mg hydrochlorothiazide

excipients: pregelatinized starch - 17 mg; colloidal silicon dioxide (Aerosil) - 1.5 mg; monohydrate lactose (milk sugar) - 40 mg; magnesium stearate - 0.75 mg; MCC - 32 mg

shell film: Selekoat AQ-02140 / A (Valium - hydroxypropyl - 1.65 mg macrogol - polyethylene glycol 400 - 0.27 mg macrogol - polyethylene glycol 6000 - 0.42 mg of titanium dioxide - 0.63 mg dye "Sunny sunset "yellow - 0.03 mg) - 3 mg

Tablets, film-coated Table 1.

active substance:

bisoprolol fumarate (bisoprolol hemifumarate), 5 mg

6.25 mg hydrochlorothiazide

Additional ingredients: colloidal silicon dioxide (Aerosil) - 2.1 mg; pregelatinized corn starch (starch C * Rharm 93000) - 23.9 mg; lactose (milk sugar) - 70 mg; magnesium stearate - 0.75 mg; MCC - 32 mg

shell film: Selekoat AQ-02140 (hypromellose - hydroxypropyl - 2.2 mg, macrogol - polyethylene glycol 400 - 0.36 mg macrogol - polyethylene glycol 6000 - 0.56 mg titanium dioxide - 0.84 mg dye "sunset" yellow - 0.04 mg), - 4 mg

The drug forms

Tablets, 2.5 mg + 6.25 mg: film-coated yellow-orange color, round, biconcave, with cross mark. In cross section: two layers, the inner layer nearly white.

Tablets 5 mg + 6.25 mg: film-coated yellow-orange color, round, biconcave. In cross section: two layers, the shell of yellow-orange, white core.

pharmachologic effect

antianginal, diuretic, hypotensive, antiarrhythmic, beta-adrenoceptor blocking.

pharmacodynamics

Aritel® Plus - combined preparation, which consists of bisoprolol and hydrochlorothiazide.

bisoprolol

Selective β1-blocker without intrinsic sympathomimetic activity. It has antihypertensive, antiarrhythmic and antianginal effects. Lock in low doses β1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effects (heart rate slows, inhibits cardiac conduction, reduces the excitability and myocardial contractility) . With increasing doses of β2-adrenergic receptors blocks.

PR at the beginning of the use of β-blockers in the first 24 hours is increased (as a result of reciprocal increase in the activity of α-adrenoceptor stimulation and removal of β2-adrenergic receptors), after 1-3 days back to the original, but with long-term appointment is reduced.

The hypotensive effect was associated with reduced cardiac output, the suppression of the sympathetic stimulation of peripheral blood vessels, reduction in activity of the RAAS by inhibiting the β-adrenoceptor juxtaglomerular kidney machine (which leads to a decrease in renin secretion), restoration of the sensitivity of the baroreceptors of the aortic arch (not occurs enhancing their activity in response to a decrease AD) and the influence of the central nervous system. When hypertension effect develops after 2-5 days, stable operation - through 1-2 months.

hydrochlorothiazide

Thiazide diuretics. It reduces the reabsorption of sodium in the cortical segment of the loop of Henle, without affecting its portion extending into the renal medulla. Blocks carbonic anhydrase in the proximal convoluted tubule, increases the excretion of kidney potassium ions, phosphates and bicarbonates. Virtually no effect on acid-base status. Increases renal excretion of magnesium ions; delays in the body of calcium ions and inhibits the excretion of urate. The diuretic effect develops in 1-2 hours, reaches a maximum after 4 hours, maintained for 6-12 hours. The diuretic effect decreases with a decrease in glomerular filtration rate, and it stops at the value of less than 30 ml / min.

Pharmacokinetics

bisoprolol

After oral absorption from the gastrointestinal tract is 80-90%. Food does not affect the extent of absorption. Plasma Tmax is 2-4 hours. Communication plasma proteins about 30%. Poor penetrate the BBB and placental barrier. The secretion of breast milk is insignificant. It is metabolized in the liver. T1 / 2 -. 9-12 hours excreted by the kidneys (50% - unchanged), less than 2% - through the intestines.

hydrochlorothiazide

If ingestion is rapidly absorbed, but incomplete. Tmax in the blood plasma is about 4 hours Bioavailability -. 60-80%. Communication to plasma proteins is 40%. It penetrates through the placental barrier and is excreted in breast milk. Do not metabolized. It reports the news, largely unaltered by glomerular filtration and active tubular secretion. T1 / 2 - about 8 hr.

Indications of the drug Aritel® Plus

Hypertension mild to moderate severity.

Contraindications

Hypersensitivity to bisoprolol and other ingredients;

hypersensitivity to hydrochlorothiazide or other sulfonamides;

bronchial asthma;

chronic obstructive pulmonary disease;

decompensated chronic heart failure (CHF);

cardiogenic shock;

syndrome sick sinus (including sinoatrial block);

AV blockade II and III level without pacemaker;

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

variant angina (Prinzmetal angina);

pheochromocytoma (without α-blockers simultaneous use);

unmanageable diabetes;

The expressed disturbances of peripheral circulation (including Raynaud's syndrome);

severe hypotension (Sad less than 100 mm Hg..);

Refractory hypokalaemia, hyponatraemia, hypercalcaemia;

metabolic acidosis;

hypovolemia;

acute renal failure;

chronic renal failure (Cl creatinine less than 30 ml / min);

simultaneous use with floctafenine, sultopride;

concomitant use of antiarrhythmic drugs;

concomitant use of drugs lithium;

simultaneous MAO inhibitors (except for MAO-B inhibitors);

lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

pregnancy;

lactation;

age of 18 years (effectiveness and safety have been established).

Precautions: conducting desensitizing therapy; AV block of I degree; psoriasis; cardiac ischemia; liver failure; renal failure (Cl creatinine more than 30 ml / min); hyperthyroidism; pheochromocytoma (during treatment with α-blockers); hyperthyroidism; water and electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia); gout; restrictive cardiomyopathy; congenital heart defect or heart valve with severe hemodynamic impairment; strict diet; depression (including history); myasthenia gravis; Elderly patients.

Pregnancy and breast-feeding

Contraindicated in pregnancy and during breastfeeding.

Side effects

From the central and peripheral nervous system: fatigue, asthenia, anxiety, dizziness, headache, drowsiness or insomnia, depression, memory / attention disorder, syncope, vertigo, feeling cold and numb limbs, convulsions, paraesthesia, hypoesthesia, hyperesthesia, hallucinations , nightmares.

From the CCC: sinus bradycardia, marked reduction in blood pressure, disturbance of AV conduction, ventricular arrythmia, postural hypotension, worsening of heart failure flow, peripheral edema.

The respiratory system: in predisposed patients - laryngo and bronchospasm, dyspnea, rhinitis, sinusitis, pharyngitis, nasal congestion.

From the digestive system: abdominal pain, peptic ulcer, gastritis, dyspepsia, dry 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 senses: blurred vision, impaired hearing, reduced production of lachrymal glands (to be considered in patients who use contact lenses), dryness and soreness of eyes, conjunctivitis.

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

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

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

For the skin: rash, acne, pruritus, increased sweating, flushing of the skin, exfoliative dermatitis, exacerbation of psoriasis, alopecia.

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

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

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

Interaction

With the simultaneous use of the drug Aritel® Plus with phenytoin (with on / in the introduction) and drugs for inhalation general anesthesia (derivatives of hydrocarbons) can amplify the severity cardiodepressive action and the probability of excessive reduction of blood pressure (due to the content in the composition of the drug bisoprolol).

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

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

Plus Aritel® contraindicated for use in combination with floctafenine, sultopride, MAO inhibitors (MAO inhibitors with the exception of type B).

Perhaps strengthening the hypotensive effect of the drug Aritel® Plus, while the use of antidepressants, neuroleptics, CCB (amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), ACE inhibitors (including captopril, enalapril), irbesartan, diuretics, clonidine, sympatholytic, hydralazine and other antihypertensives.

Possible weakening of the hypotensive effect of the drug Aritel® Plus, while the appointment with corticosteroids (for regular use), estrogens, NSAIDs (indomethacin, piroxicam, naproxen, phenylbutazone) and tetrakozaktidom.

While the use of the drug Aritel® Plus may increase the effects of non-depolarizing muscle relaxants and anticoagulant effect of coumarin derivatives.

Cardiac glycosides, methyldopa, reserpine, guanfacine, CCB (verapamil, diltiazem, amlodipine, felodipine, nifedipine, nicardipine, nimodipine, nitrendipine), antiarrhythmic agents, as well as tools that can initiate arrhythmia type "pirouette" (astemizole, erythromycin, pentamidine, sparfloxacin, terfenadine), increase the risk of development and / or enhancement of bradycardia, AV block, and heart failure.

In an application with sotalol possible hypokalemia and development of "pirouette" type of ventricular arrhythmia.

With the simultaneous use of the drug Aritel® Plus with lithium salts may increase the concentration of the latter in the blood to toxic levels.

The effectiveness of insulin and hypoglycemic agents for the reception may fall into.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

With the simultaneous use of the drug Aritel® Plus allergens used for immunotherapy, or allergen extracts for skin tests, as well as with allopurinol or iodine radiopaque diagnostic tools for the in / in the introduction, the risk of allergic reactions.

When concomitant administration of the drug Aritel® Plus with mefloquine may develop bradycardia; carbamazepine - hyponatremia; with cyclosporine - elevation of serum creatinine.

Sulfasalazine increases the concentration of bisoprolol in blood plasma; rifampicin - shortens the T1 / 2 bisoprolol.

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

Dosing and Administration

Inside, swallowing whole, without chewing, with a small amount of water. Aritel® Plus is recommended to take in the morning, during a meal.

The recommended starting dose is 2.5 mg bisoprolol + hydrochlorothiazide 6.25 mg 1 time per day.

For individual adjustment of the dosage Aritel® Plus is available in the following doses: 2.5 mg bisoprolol and 6.25 mg hydrochlorothiazide; Bisoprolol 5 mg and 6.25 mg of hydrochlorothiazide.

Each subsequent increase in dose should be carried out not less than 2 weeks.

If an increase in the dose of the drug is poorly tolerated by the patient, the dose may be reduced.

Patients with moderately impaired liver and kidney function and elderly patients dose adjustment is required.

In patients with severely impaired liver and kidney (Cl creatinine more than 30 ml / min) the maximum daily dose of bisoprolol should not exceed 10 mg.

Course duration is set by your doctor.

Overdose

Symptoms: marked reduction of blood pressure, bradycardia, congestive heart failure, ventricular premature beats, AV block, convulsions, bronchospasm.

Treatment: gastric lavage, the appointment of absorbent, symptomatic therapy. In the case of pronounced reduction in blood pressure is necessary to give the patient a horizontal position with raised legs, to take measures to compensate for the BCC. Bradycardia / v atropine at a dose of 1-2 mg, glucagon in a dose of 12 mg (slow bolus), if necessary - as an infusion at a dose of 1.10 mg / hr. Subsequently assigned epinephrine (adrenaline) at a dose of 15-85 mg (introduction which can be repeated, but the total should not exceed 300 micrograms) or dopamine at a dose of 2.5-10 mg / kg / min. In acute heart failure shows the cardiac glycosides, diuretics, glucagon. If there are no signs of pulmonary edema, the I / appointed plazmozameschayuschie solutions at their inefficiency - epinephrine, dopamine, dobutamine. When ventricular arrhythmia applied lidocaine. In which developed AV blockade should be in / to enter the 1-2 mg of atropine, epinephrine, or install a temporary pacemaker. In convulsions diazepam recommended I / O. When bronchospasm inhaled β2-agonists are administered.

special instructions

During therapy with Aritel® Plus requires monitoring of heart rate and blood pressure (at the beginning of treatment - daily, then - 1 every 3-4 months), the blood glucose in patients with diabetes (1 every 4-5 months). Elderly patients should be started with the formulation of the preparation containing a low dose of bisoprolol. This requires regular monitoring of patients, it is also recommended to monitor renal function (1 every 4-5 months). It is necessary to train the patient's heart rate calculation method.

It is necessary to reduce the dose Aritel® Plus (by reducing the content in the bisoprolol) if resting heart rate is less than 50-55 u. / Min.

During therapy with Aritel® Plus must also monitor the performance of acid-base status and electrolytes (potassium, sodium, calcium).

Particular attention is required in cases of surgery under general anesthesia in patients receiving β-blockers. Such patients should be abolished Aritel® Plus 48 hours before surgery, to prevent an anesthesiologist that the patient takes the drug Aritel® Plus. As a means for general anesthesia should choose the drug with minimal negative inotropic effect.

bisoprolol

Discontinuation of therapy should be gradual, particularly with concomitant coronary heart disease. Reduce the dose over 2 weeks. If necessary, carry out the appropriate therapy to prevent strokes.

In bronchial asthma and COPD treatment is initiated with a minimum dose. Pre conduct functional respiratory tests. With the development of bronchospasm prescribed β-agonists.

When concomitant heart failure treatment is carried out under the supervision of a doctor, in minimal doses.

Given the negative effect of dromotropic β-blockers should be used with caution in patients with AV blockade of I degree.

In patients with peripheral circulatory disorders (Raynaud's disease) β-blockers may exacerbate the disease, so the drug is contraindicated in these patients (see. "Contraindications").

When thyrotoxicosis Aritel® Plus (due to content in the bisoprolol) may mask clinical signs (eg tachycardia).

Patients with pheochromocytoma should not be prescribed the drug as long as not been treated α-blockers. During treatment requires monitoring of blood pressure.

It is recommended to discontinue therapy with Aritel® Plus in the development of depression caused by taking β-blockers (due to content in the bisoprolol). Elderly patients are treated with a low dose, the patient under control.

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

Patients who use contact lenses, you should be careful when using the drug Aritel® Plus, as β-blockers may reduce the production of the lacrimal gland.

Therapy β-blockers may exacerbate psoriasis.

Patients who have a history of anaphylactic reactions (especially floctafenine or desensitizing drugs), β-blocker treatment can exacerbate these reactions and lead to the development of resistance to conventional doses of epinephrine.

Athletes should be informed that this drug may produce false-positive results during doping tests.

hydrochlorothiazide

Necessary to control the level of sodium in the blood (especially in the elderly and in liver cirrhosis). It is necessary to control the concentration of potassium in the blood of elderly patients with cirrhosis, accompanied by edema, ascites, coronary artery disease or heart failure, with prolonged QT interval. Hypokalemia increases the risk of arrhythmias, increases the toxicity of cardiac glycosides. The first definition of the concentration of potassium in the blood must be held during the 1st week of treatment.

Thiazides may decrease urinary excretion of calcium, which leads to a temporary hypercalcemia. Temporary hypercalcemia may be related to undiagnosed hyperparathyroidism.

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

Thiazide diuretics are effective at normal or slightly reduced (creatinine concentration less than 25 mg / ml, or 220 mmol / l) renal function.

Hypovolemia leads to the reduction of glomerular filtration, which leads to an increase in urea and creatinine in the blood of patients with normal renal function. In patients with chronic renal failure may increase the existing violations.

It is necessary to cancel prior to the study in blood and urine catecholamines and Normetanephrine vanillylmandelic acid; titers of antinuclear antibodies.

Effects on ability to drive and use machines. During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.

release Form

Tablets, film-coated, 2.5 mg + 6.25 mg. In blisters made of PVC film and aluminum foil printed patent for 7, 10 or 30 pieces. 1, 2, 4 blisters on 7 pcs. or 1, 2, 3, 5, 10 contour of cellular packages 10 pcs. or 1, 3 blisters to 30 pcs. a stack of cardboard.

Tablets, film-coated, 5 mg + 6.25 mg. In blisters made of PVC film and aluminum foil printed lacquered 10, 15 or 30 pieces. 1, 3, 6 contour cell packages of 10 pieces. or 2, 4 blisters to 15 pcs. or 1, 2 blisters to 30 pcs. a stack of cardboard.

Conditions of supply of pharmacies

On prescription.

Storage condition

In a dry, dark place at a temperature no higher than 25 ° C.

Keep out of the reach of children.

Shelf-life

2 years.

Do not use beyond the expiration date printed on the package.