Bisangil - instructions for use, dose, side effects, contraindications

auxiliary substances (core): Monohydrate lactose (milk sugar) 62.0 mg Microcrystalline cellulose 18.0 mg Croscarmellose sodium 2.0 mg, 4.75 mg corn starch, povidone (polyvinylpyrrolidone) 3.5 mg Magnesium stearate 1.0 mg;

auxiliary substances (shell): 1.65 mg of hypromellose, macrogol 4000 0.45 mg titanium dioxide 0.9 mg.

Each tablet of 5.0 mg + 6.25 mg contains:

active substances: bisoprolol fumarate 5.0 mg and hydrochlorothiazide 6.25 mg;

auxiliary substances (core): monohydrate lactose (milk sugar) 130.25 mg Microcrystalline cellulose 36.0 mg Croscarmellose sodium 4.0 mg, 9.5 mg of corn starch, povidone (polyvinylpyrrolidone) 7.0 mg Magnesium stearate 2.0 mg;

auxiliary substances (shell): hypromellose, 3.3 mg, macrogol 4000 0.9 mg, titanium dioxide 1.8 mg.

Description:

Round tablets of biconvex form, covered with a film coat of white or almost white color.

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

ATX: & nbsp

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

Pharmacodynamics:

Bisoprolol - selective beta₁-adrenoceptor without internal sympathomimetic activity. Has antihypertensive, antiarrhythmic and anti-anginal action. Blocking in low doses of beta₁(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, beta blocks₂-adrenoceptors. The total peripheral vascular resistance at the beginning of beta-blockers application increases in the first 24 hours (as a result of the reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of beta stimulation₂-adrenoreceptors), after 1-3 days it returns to the initial, and with a long-term administration decreases.

The antihypertensive 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 beta-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 after 2-5 days, stable effect - after 1-2 months of therapy.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic, it disrupts the reabsorption of sodium, chlorine, potassium, magnesium ions in the distal nephron, delays the excretion of calcium, uric acid. The increase in renal excretion of these ions is accompanied by an increase in the amount of urine (due to the osmotic binding of water). Hydrochlorothiazide reduces the volume of blood plasma, increases the activity of renin in the blood plasma and the secretion of aldosterone.When taken in high doses hydrochlorothiazide increases the excretion of bicarbonates, with prolonged intake reduces calcium excretion.

Antihypertensive effect develops due to a decrease in the volume of circulating blood (BCC), changes in the reactivity of the vascular wall, decrease of the pressor influence of vasoconstrictive amines (epinephrine, norepinephrine): and intensification of the depressor effect on the ganglion. Does not affect normal blood pressure (BP). Diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours.

Antihypertensive effect occurs in 3-4 days, but to achieve the optimal therapeutic effect, 3-4 weeks is necessary.

Pharmacokinetics:

Bisoprolol

Bisoprolol is almost completely absorbed in the gastrointestinal tract, eating does not affect absorption. The effect of "primary passage" through the liver is negligible, which leads to high bioavailability (about 90%).

Bisoprolol metabolized along the oxidative pathway without subsequent conjugation. All metabolites have a strong polarity and are excreted by the kidneys. The main metabolites found in blood plasma and urine,do not show pharmacological activity. Data obtained as a result of experiments with microsomes of human liver in vitro, show that bisoprolol is metabolized primarily by isoenzyme CYP3A4 (about 95%), and isoenzyme CYP2D6 plays only a minor role.

The connection with blood plasma proteins is about 30%. The volume of distribution is 3.5 l / kg. The total ground clearance is approximately 15 l / h. The maximum concentration in the blood plasma is determined after 2-3 hours. Permeability through the blood-brain barrier and the placental barrier is low.

The half-life of blood plasma (10-12 hours) provides efficacy in for 24 hours after taking a single daily dose.

Bisoprolol is excreted from the body in two ways, 50% of the dose is metabolized in the liver with the formation of inactive metabolites. About 98% is excreted by the kidneys, of which 50% is excreted unchanged; less than 2% - through the intestines (with bile).

Since excretion takes place in the kidneys and in the liver equally, patients with a dysfunction of the liver or with renal insufficiency do not need to adjust the dose. The pharmacokinetics of bisoprolol is linear and does not depend on age.

Hydrochlorothiazide

After ingestion, the absorption and bioavailability of hydrochlorothiazide is about 70%. Connection with blood plasma proteins - 60-80%.

When ingestion of 12.5 mg of hydrochlorothiazide, the maximum plasma concentration is achieved after 1.5-4 hours and is 70 ng / ml, and when administered 25 mg of hydrochlorothiazide, the maximum plasma concentration is reached after 2-5 hours and is 142 ng / ml.

In the therapeutic range of doses, the average area under the "concentration-time" curve (AUC) increases in direct proportion to the increase in dose, with the appointment of once a day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. The half-life (T_1/2) - 5-6 hours Hydrochlorothiazide slightly metabolized in the liver. Hydrochlorothiazide is excreted almost completely (more than 95%) by the kidneys in unchanged form, 50-70% of the dose taken inside is excreted within 24 hours.

Indications:

Arterial hypertension of mild and moderate severity.

Contraindications:

- Hypersensitivity to bisoprolol and other components of the drug;

- hypersensitivity to hydrochlorothiazide and other sulfonamide derivatives;

- severe forms of bronchial asthma and chronic obstructive pulmonary disease;

- acute heart failure or chronic heart failure in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

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

- atrioventricular block II and III degree without an artificial pacemaker;

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

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

- difficultly controlled diabetes mellitus;

- late stages of peripheral circulatory disorders (including Raynaud's syndrome);

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

- refractory hypokalemia, hyponatremia, hypercalcemia;

- metabolic acidosis;

- acute renal insufficiency;

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

- severe violations of the liver, including coma and precoma;

- simultaneous application with floktaphenin, sultopride;

- 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:

With caution should be used for heart failure, atrioventricular blockade of the first degree, prinzmetal angina, peripheral circulation disorders, coronary heart disease, hepatic insufficiency, renal failure (QC more than 30 ml / min); hyperthyroidism, pheochromocytoma (against the background of treatment with alpha-adrenoblockers), water-electrolyte disorders (hyponatremia, hypokalemia, hypercalcemia); depression, including a history, myasthenia gravis, gout, psoriasis, as well as in elderly patients, hyperuricemia, diabetes mellitus with significant fluctuations in blood glucose concentration, strict diet, hypovolemia, bronchial asthma, bronchospasm (in anamnesis), desensitizing therapy.

Pregnancy and lactation:

The use of Bisangyl is contraindicated in pregnancy.

At the present time, it is not known whether bisoprolol with breast milk.

Diuretics from the group of thiazides are excreted in breast milk and therefore breast-feeding during treatment with Bisangyl is not recommended. If the drug is needed during lactation, breastfeeding should be discarded.

Dosing and Administration:

Bisangil is recommended in the morning (during meals). Tablets should be swallowed whole, not liquid, squeezed with a small amount of liquid, once a day.

The dose of the drug should be selected individually.

The initial dose of the drug Bisangil - 1 tablet 2.5 mg / 6.5 mg (bisoprolol 2.5 mg / hydrochlorothiazide 6.25 mg) once a day. If the antihypertensive effect is insufficient dose increase (after 2 weeks) - 1 tablet 5 mg / 6.25 mg (bisoprolol 5 mg / hydrochlorothiazide 6.25 mg) once a day.

Patients with impaired liver function, as well as patients of advanced age, do not need to adjust the dosage regimen.

In patients with impaired renal function (QC more than 30 ml / min.), The maximum daily dose of bisoprolol should not exceed 10 mg.

Side effects:

Bisoprolol

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): very often - not less than 10%; often - not less than 1%,but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including individual reports.

From the side of the heart and blood vessels: very often - a decrease in heart rate (bradycardia, especially in patients with chronic heart failure (CHF)); a feeling of palpitations; often a marked decrease in blood pressure (especially in patients with CHF), manifestation of angiospasm (increased peripheral circulatory disturbances, sensation of coldness in the extremities (paresthesia), infrequent infringement of atrioventricular (AV) conduction (up to the development of complete transverse blockade and cardiac arrest), arrhythmias, orthostatic hypotension, aggravation of CHF flow with development of peripheral edema (swelling of the ankles, stop, shortness of breath), chest pain.

From the nervous system: often - dizziness, headache, asthenia, fatigue, sleep disorders, depression, anxiety; rarely - confusion or short-term memory loss, "nightmarish" dreams, hallucinations, myasthenia gravis, tremor, muscle cramps. Usually, these phenomena are of an easy nature and usually take place within 1-2 weeks after the start of treatment.

From the sense organs: rarely - impaired vision, reduced tearing (should be taken into account when wearing contact lenses), tinnitus, hearing loss, ear pain; very rarely - dryness and soreness of the eyes, conjunctivitis, taste disorders.

From the respiratory system: infrequently bronchospasm in patients with bronchial asthma or obstructive airway disease; rarely allergic rhinitis; nasal congestion.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dryness of the oral mucosa, abdominal pain; rarely - hepatitis, increased activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase), increased bilirubin concentration, change in taste.

From the musculoskeletal system: infrequently - arthralgia, pain in the back.

From the genitourinary system: very rarely - a violation of potency, a weakening of the libido.

Laboratory indicators: rarely - an increase in the concentration of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis, and leukopenia.

Allergic reactions: rarely - skin itching, rash, urticaria

From the skin: rarely - increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions; very rarely - alopecia, beta-adrenoblockers can aggravate the course of psoriasis.

Other: syndrome of "withdrawal" (increased frequency of angina attacks, increased blood pressure).

Hydrochlorothiazide

Violation of the water-electrolyte balance: hypokalemia, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis: dryness of the oral mucosa, thirst, irregular heart rhythm, changes in mood or psyche, convulsions and muscle pain, nausea, vomiting, unusual fatigue or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia: confusion, convulsions, lethargy, slowing the process of thinking, increased fatigue, excitability, muscle cramps.

Metabolic disorders: hyperglycemia, glucosuria, hyperuricemia with the development of an attack of gout.

Treatment with thiazides can impair glucose tolerance, and latent diabetes mellitus can manifest. When using high doses, lipid concentrations in the serum can increase.

From the digestive system: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the side of the heart and blood vessels: arrhythmias, orthostatic hypotension, vasculitis.

From the nervous system: dizziness, temporarily blurred vision, headache, paresthesia.

From the hematopoiesis: very rarely - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Allergic reactions: urticaria, purpura, necrotizing vasculitis, syndrome Stevens-Johnson, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.

Other phenomena: decreased potency, impaired renal function, interstitial nephritis.

Overdose:

Bisoprolol

The most frequent symptoms of beta-adrenoblocker overdose are: marked decrease in blood pressure, bradycardia, atrioventricular blockade, bronchospasm, acute heart failure and hypoglycemia.

Hydrochlorothiazide

Clinical manifestations of acute or chronic overdose of hydrochlorothiazide are due to a significant loss of fluid or electrolytes.

The most frequent symptoms of hydrochlorothiazide overdose: dizziness, nausea, drowsiness, hypovolemia, marked decrease in blood pressure, hypokalemia.

Treatment:

In case of an overdose, first of all, it is necessary to stop taking the drug, rinse the stomach, prescribe adsorptive agents and begin to maintain maintenance symptomatic therapy.

With a pronounced bradycardia: intravenous administration of atropine. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With a pronounced decrease in blood pressure: intravenous injection of plasma-substituting solutions.

With atrioventricular blockade (II and III degree): patients should be under constant supervision, it is possible to prescribe epinephrine, if necessary - staging an artificial pacemaker.

With exacerbation of chronic heart failure: intravenous injection of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

When bronhospazme: bronchodilators, beta₂symmetrimimetics and / or aminophylline.

When hypoglycemia: intravenous administration of a solution of dextrose (glucose).

Interaction:

Bisoprolol

Combinations, the use of which is contraindicated

In the case of shock or arterial hypotension caused by the use of floktaphenina, beta-adrenoblockers cause a decrease in compensatory cardiovascular reactions.

Bisoprolol should not be used concomitantly with sultopride, since there is a high risk of ventricular arrhythmias, including pirouettes.

MAO type A inhibitors should not be taken concomitantly with bisoprolol, since there is a risk of developing a hypertensive crisis.

Unrecommended combinations

Antiarrhythmic drugs of the first class (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone) with simultaneous application with bisoprolol may reduce AV conduction and contractility of the heart.

Blockers of "slow" calcium channels (BCCC) such as verapamil and to a lesser extent, diltiazem, with simultaneous application with bisoprolol may lead to a decrease in myocardial contractility and disruption AV conductivity. In particular, intravenous administration of verapamil to patients taking beta-blockers,can lead to severe arterial hypotension and AV blockade.

Hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in the central sympathetic tone. Abrupt abolition of antihypertensive agents of central action, especially before the abolition of beta-blockers may increase the risk of developing "ricochet" arterial hypertension.

Combinations that require caution

Antiarrhythmic drugs of the III class (for example, amiodarone) can increase the violation AV conductivity.

The action of beta-blockers for topical application (eg, eye drops for the treatment of glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, decreasing heart rate).

Parasympatomimetics with simultaneous use with bisoprolol may increase the disruption AV conductivity and increase the risk of developing a bradycardia.

Simultaneous use of Bisangyl with beta-adrenomimetics (for example, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs.The combination of bisoprolol with adrenomimetics, affecting beta and alpha-adrenoreceptors (for example, norepinephrine, epinephrine), may enhance the vasoconstrictor effects of these agents that occur with alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using nonselective beta-blockers.

Mefloquine with simultaneous application with bisoprolol may increase the risk of developing bradycardia.

Allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving bisoprolol.

Iodine-containing radiopaque diagnostic tools for intravenous administration increase the risk of anaphylactic reactions.

Phenytoin with intravenous administration, means for inhalation anesthesia (derivatives of hydrocarbons) increase the severity of cardiodepressive action and the likelihood of lowering blood pressure.

The effectiveness of insulin and hypoglycemic agents for oral administration may change with treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

The clearance of lidocaine and xanthines (except theophylline) may decrease due to a possible increase in their concentration in the blood plasma, especially in patients with initially elevated clearance of theophylline under the influence of smoking.

Antihypertensive effect weaken non-steroidal anti-inflammatory drugs (NSAIDs) (sodium ion delay and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (sodium ion delay).

Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers of "slow" calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade, cardiac arrest and heart failure.

Antiarrhythmic drugs that can cause tachycardia such as "pirouette" (class IA, eg, quinidine, hydroquidin, disopyramide and class III, for example, amiodarone, dofetilid, ibutilid) and sotalol: hypokalemia can provoke the appearance of tachycardia such as "pirouette".

Other arrhythmic agents that can cause tachycardia as pirouettes (for example, astemizole, erythromycin for intravenous administration, halofantrine, pentamidine, sparfloxacin, terfenadine, wincamine): hypokalemia can provoke the development of tachycardia such as "pirouette".

Nifedipine can lead to a significant reduction in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensives can lead to excessive blood pressure lowering.

The effect of nondepolarizing muscle relaxants and the anticoagulant effect of coumarins during treatment with bisoprolol may be prolonged.

Tricyclic and tetracyclic antidepressants, antipsychotics (antipsychotics), ethanol, sedatives and hypnotics increase the inhibition of the central nervous system.

It is not recommended simultaneous use with MAO inhibitors due to a significant increase in antihypertensive action. A break in treatment between taking MAO inhibitors and bisoprolol should be at least 14 days.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

Ergotamine increases the risk of peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens the half-life of bisoprolol.

Hydrochlorothiazide

With thiazide diuretics, such medicines as ethanol, barbiturates and narcotics, can potentiate the risk of developing orthostatic hypotension.

Hypoglycemic agents (for oral administration and insulin) - dosage correction of hypoglycemic agents may be required.

Other antihypertensives - additive effect.

Kolestyramine and colestipol - in the presence of anion-exchange resins, absorption hydrochlorothiazide but is violated. Kolestyramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, ACTH (adrenocorticotropic hormone) or glycyrrhizic acid (found in licorice root) - a marked decrease in the electrolyte content, in particular, the risk of hypokalemia.

Pressor amines (e.g., epinephrine, norepinephrine) - a decrease in the severity of response to the reception of pressor amines.

Muscle relaxants of nondepolarizing action type (eg, tubocurarine) - strengthening the effect of muscle relaxants.

Lithium - diuretics reduce renal clearance of lithium and increase the risk of toxic action of lithium; simultaneous use is not recommended.

Non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclooxygenase-2 inhibitors (COX-2)) - can reduce diuretic, natriuretic and anti-hypertensive effect of diuretics,

In some patients with impaired renal function (eg, elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, including COX-2 inhibitors, treatment with angiotensin II receptor antagonists or ACE inhibitors may cause further impairment of renal function, including development of acute renal failure. These effects are reversible. The simultaneous use of these drugs should be conducted with caution in patients with impaired renal function.

In connection with the effect on calcium metabolism, their reception may distort the results of the study of parathyroid gland function.

Special instructions:

During the period of therapy with Bisangil, blood pressure and blood pressure control is necessary (at the beginning of treatment - daily, then - once every 3-4 months), blood glucose concentrations in diabetic patients (1 every 4-5 months). In elderly patients it is recommended to monitor kidney function (1 time in 4-5 months).It is necessary to teach the patient how to calculate heart rate.

During the period of therapy with Bisangyl, it is also necessary to monitor the acid-base state and the content of electrolytes (potassium, sodium, calcium). More frequent monitoring of potassium in patients at high risk is needed.

In patients with peripheral circulatory disorders, caution should be exercised when prescribing Bisangyl.

In thyrotoxicosis, Bisangyl (due to its bisoprolol content) can mask the clinical signs of the disease (for example, tachycardia).

Patients with pheochromocytoma should not be prescribed Bisangil until treatment with alpha-blockers is prescribed. In this case, it is necessary to monitor blood pressure.

In patients with mild bronchial asthma or chronic obstructive pulmonary disease, treatment is started with a minimal dose.

It is recommended to stop therapy with Bisangyl with the development of depression caused by taking a beta-blocker (due to the content of bisoprolol in it).

In elderly patients, treatment with Bisangyl should be started with a drug dosage form,containing a low dose of bisoprolol (2.5 mg). Regular monitoring of the patients' condition is necessary.

Do not abruptly discontinue therapy, especially in patients with coronary heart disease. The dose should be reduced gradually within two weeks. If necessary, simultaneous initiation of appropriate antianginal therapy should be initiated.

Particular attention is required in cases of surgical intervention under general anesthesia in patients taking beta-blockers. Such patients should cancel the Bisangil drug 48 hours before surgery, warn the anesthesia surgeon that the patient is taking the drug Bisangil. As a means for general anesthesia, a drug with a minimum negative inotropic effect should be chosen.

On the background of therapy with beta-blockers, the exacerbation of psoriasis is possible. Patients with this disease Bisangil should be administered with caution.

In case of anamnesis, anaphylactic reactions, regardless of the cause of their occurrence, especially when conducting desensitizing therapy,treatment with Bisangyl (due to the content of bisoprolol in it) can increase the risk of allergic reactions and promote the development of resistance to epinephrine (adrenaline) treatment in usual doses.

Patients who use contact lenses should be careful when using Bisangyl, since beta-blockers can reduce the production of tears.

In patients with hyperuricemia, the risk of exacerbation of gout is increased. In this case, the dose of Bisangyl should be selected individually under the control of the concentration of uric acid in the serum.

Before the study of the function of parathyroid glands, treatment with Bisangyl should be stopped, as transient hypercalcemia may occur on the background of its administration.

Athletes should be informed that the drug Bisangil contains bisoprolol, which can give false positive results in the conduct of doping control.

Effect on the ability to drive transp. cf. and fur:

Bisangyl should be used with caution in the management of vehicles and mechanisms in connection with the possibility of developing dizziness.

Form release / dosage:

Tablets, film-coated, 2.5 mg + 6.25 mg and 5 mg + 6.25 mg.

Packaging:

For 10, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50 or 100 tablets into a polymer container for medicines.

One container or 1, 2, 3, 4, 5 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001447

Date of registration:23.01.2012

Expiration Date:23.01.2017

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Bisangil (Bisangil)