Active substanceLercanidipine + EnalaprilLercanidipine + Enalapril
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  • Coripren®
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  • Enap® L Combi
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    KRKA-RUS, LLC     Russia
  • Dosage form: & nbspfilm-coated tablets
    Composition:

    One film-coated tablet contains:

    active ingredients: lercanidipine hydrochloride 10 mg + enalapril maleate 10 mg or lercanidipine hydrochloride 10 mg + enalapril maleate 20 mg;

    Excipients: lactose monohydrate 102 mg / 92 mg, microcrystalline cellulose 40 mg, sodium carboxymethyl starch 20 mg, povidone-K30 8 mg, sodium hydrogen carbonate 8 mg, magnesium stearate 2 mg;

    composition of the shell:

    dosage of 10mg + 10mg: opada white (02F29056) 6 mg [hypromellose-5cP 3.825 mg, titanium dioxide (E171) 1.275 mg, talc 0.3 mg, macrogol-6000 0.6 mg];

    dosage of 10 mg + 20 mg: opada yellow (02F22330) 6 mg [hypromellose-5cP 3.825 mg, titanium dioxide (E171) 1.139 mg, talc 0.3 mg, macrogol-6000 0.6 mg, dye quinoline yellow (E104) 0.121 mg, ferric oxide yellow oxide (E172) 0.015 mg] .

    Description:

    Dosage of 10mg + 10mg: Round biconvex tablets, covered film shell of white color; on the cross-section the nucleus is light yellow in color.

    Dosage of 10 mg + 20 mg: Round biconvex tablets, covered with a film coating of yellow color; on the cross-section the nucleus is light yellow in color.

    Pharmacotherapeutic group:The hypotensive agent combined (angiotensin-converting enzyme inhibitor + blocker of "slow" calcium channels)
    ATX: & nbsp

    C.09.B.B   ACE inhibitors in combination with calcium channel blockers

    C.09.B.B.02   Lercanidipine and enalapril

    Pharmacodynamics:

    The drug is a combination of an angiotensin-converting enzyme (ACE) inhibitor and a blocker of "slow" calcium channels (BCCA).

    Lercanidipine

    Lercanidipine, a dihydropyridine derivative, inhibits the transmembrane flow of calcium into cardiac cells and smooth muscle cells. The mechanism of antihypertensive action is due to direct relaxing action on the smooth muscles of the vessels, as a result of which the overall peripheral resistance of the vessels decreases. Has a prolonged antihypertensive effect. Due to the high selectivity to the smooth muscle cells of the vessels, a negative inotropic effect is absent.

    Enalapril

    Enalapril - ACE inhibitor, inhibits the formation of angiotensin II and eliminates its vasoconstrictive effect. Reduces blood pressure without causing an increase in heart rate and minute volume.Reduces the overall peripheral vascular resistance, reduces afterload and preload on the heart. Reduces pressure in the right atrium and a small circle of blood circulation. Does not affect the metabolism of glucose, lipoproteins, as well as the functions of the reproductive system.

    Pharmacokinetics:

    There are no pharmacokinetic interactions with concurrent use of lercanidipine and enalapril.

    Lercanidipine

    - suction: lercanidipine absorbed completely (in the gastrointestinal tract (GIT)) after ingestion. At "primary passage" through the liver, due to high metabolism, absolute bioavailability after ingestion after eating is approximately 10%, when taken on an empty stomach, bioavailability decreases by 1/3. Bioavailability after lercanidipine is increased 4-fold if the drug is taken no later than 2 hours after ingestion of fatty foods. Therefore, the drug should be taken at least 15 minutes before meals. The maximum concentration of lercanidipine in the blood plasma (Cmah) is observed after 1.5-3 hours. Do not cumulate with repeated use. The duration of the therapeutic action of lercanidipine is 24 hours.

    The concentration of lercanidipine in blood plasma when taken orally is not directly proportional to the dosage (non-linear dependence). When taking 10 mg, 20 mg or 40 mg, the maximum concentration of lercanidipine in the blood plasma was determined in a ratio of 1: 3: 8, respectively, and the area under the concentration-time curve (AUC) - in a ratio of 1: 4: 18, which suggests a progressive saturation in the "primary passage" through the liver. Accordingly, bioavailability increases with increasing dose.

    - distribution: The distribution of lercanidipine from plasma to tissues and organs occurs rapidly and intensively. The binding of lercanidipine to plasma proteins exceeds 98%. In patients with renal and hepatic insufficiency, the plasma protein content is reduced, so the free fraction of lercanidipine can be increased.

    - metabolism: lercanidipine metabolized by the isoenzyme of the liver CYP3A4 with the formation of non-active metabolites.

    - excretion: the drug in an unchanged form is practically not found in urine and feces. About 50% of the accepted dose of lercanidipine is excreted by the kidneys, the average value of the half-life (T1 / 2) of lercanidipine is 8-10 hours.

    In elderly patients and patients with mild or moderate renal failure or with mild or moderate hepatic insufficiency, the pharmacokinetic parameters of lercanidipine are similar to those in the general group of patients. In patients with severe renal failure or in patients on hemodialysis, lercanidipine is excreted by the kidneys in a higher quantity (about 70%). In patients with hepatic insufficiency (from moderate to severe), the systemic bioavailability of lercanidipine is increased, since the drug is metabolized predominantly in the liver.

    Enalapril

    - suction: the percentage of absorption of enalapril after ingestion of about 60%. FROMmenalapril in the blood plasma is observed after 1 hour. Eating does not affect the absorption of enalapril.

    - distribution: when ingested quickly hydrolyzed to enalaprilata, which has an inhibitory effect on ACE. The maximum concentration of enalaprilat in the blood serum is observed 3-4 hours after taking the drug. The binding of enalapril to plasma proteins does not exceed 60%.

    - metabolism: when ingested, it is hydrolyzed to the main metabolite, enalaprilate.

    - excretion: about 40% of enalapril in the form of enalaprilat and about 20% of unaltered enalapril is excreted by the kidneys.

    In patients with renal failure, the duration of the action of enalapril and enalaprilate is increased.

    In patients with mild or moderate renal insufficiency (creatinine clearance 40-60 ml / min) with the intake of 5 mg enalapril once a day, the plateau stage of the area under the concentration-time curve (AUC) Enalaprilat is doubled compared to patients with normal liver function. In patients with severe renal insufficiency (creatinine clearance 30 ml / min), the area under the concentration-time curve increases approximately 8-fold. In this stage of renal insufficiency, T1 / 2 enalaprilat increases with ^ repeated intake of enalapril maleate and the time to reach the plateau stage of the area under the "concentration-time" curve slows down.

    Enalaprilat can be removed from the general blood flow through hemodialysis. The dialysis clearance is 62 ml / min.

    Indications:

    Dosage of 10 mg + 10 mg: essential hypertension (with inefficiency of monotherapy with lercanidipine 10 mg).

    Dosage of 10 mg + 20 mg: essential hypertension (with inefficiency of monotherapy with enalapril 20 mg).

    Contraindications:

    - hypersensitivity to lercanidipine, enalapril or to any other ACE inhibitor and other BCCC derived dihydropyridine, as well as to any other component of the drug;

    - disorders of outflow from the left ventricle, including stenosis of the aortic valve;

    - chronic heart failure in the stage of decompensation;

    - hereditary and / or idiopathic angioedema;

    - unstable angina;

    - the first month after myocardial infarction (within 28 days);

    - severe renal failure (creatinine clearance less than 30 ml / min), including patients on hemodialysis;

    - severe hepatic impairment;

    - simultaneous use with potent inhibitors of isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, ritonavir, troleandomycin), cyclosporine, grapefruit juice;

    - angioneurotic edema from the use of ACE inhibitors (in the anamnesis);

    - presence in the anamnesis of a hereditary or idiopathic edema;

    - deficiency of lactase, lactose intolerance and glucose-galactose malabsorption syndrome;

    - children's age (under 18 years).

    Carefully:

    - syndrome of weakness of the sinus node (without simultaneous application of an artificial pacemaker);

    - a violation of the function of the left ventricle and coronary heart disease;

    - renal failure (creatinine clearance more than 30 ml / min);

    - Renovascular hypertension;

    - condition after kidney transplantation (application experience is limited);

    - liver failure;

    - oppression of bone marrow hematopoiesis;

    - severe autoimmune diseases of connective tissue (including scleroderma, systemic lupus erythematosus);

    - simultaneous use with immunosuppressants, allopurinol, procainamide;

    - diabetes;

    - surgical interventions and general anesthesia;

    - Patients who follow a diet with restricted intake of table salt;

    - hyperkalemia;

    - conditions, accompanied by a decrease in the volume of circulating blood (BCC), including diarrhea, vomiting, primary aldosteronism.

    Pregnancy and lactation:

    The use of the drug Coripren® is not recommended during pregnancy, and not only in the II and III trimesters.

    ACE inhibitors can cause disease or death of the fetus or newborn in appointments in the second and third trimesters of pregnancy.The use of ACE inhibitors during this period was accompanied by a negative impact on the fetus and newborn, including the development of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones in a newborn. Perhaps the development of oligohydramnion, apparently due to a decrease in the function of the kidneys of the fetus. This complication can lead to limb contracture, deformation of the bones of the skull, including its facial part, and lung hypoplasia.

    Teratogenic effect with the use of ACE inhibitors (enalapril) in the first trimester is not proven, but do not exclude this possibility. Patients on therapy with ACE inhibitors in pregnancy planning should switch to alternative regimens of antihypertensive treatment.

    It is not recommended to use the drug in women of childbearing age who do not use reliable contraceptives.

    The use of the drug in the period of breastfeeding is not recommended, since enalapril and its main metabolite - enalaprilate penetrate into breast milk.

    Dosing and Administration:

    Inside, preferably in the morning at least 15 minutes before eating, without chewing, squeezed enough water. You can not drink it grapefruit juice.

    Coryprene® is not intended for the initial treatment of hypertension. Dosage 10 mg + 10 mg: with ineffectiveness of monotherapy with lercanidipine 10 mg, you should start taking Coripren ® 10 mg + 10 mg.

    Dosage of 10 mg + 20 mg: with inefficiency of monotherapy with enalapril 20 mg, you should start taking Coripren ® 10 mg + 20 mg.

    The dose of the drug is selected by the doctor.

    Side effects:

    WHO classification: very often - 1/10 appointments, often - 1/100 appointments, not often - 1/1000 appointments, rarely - 1/10000 appointments, very rarely - less than 1/10000 appointments.

    Lercanidipine + enalapril

    From the central nervous system: often - dizziness; not often - a headache.

    From the side of the psyche: not often - anxiety.

    From the skin: not often - dermatitis, edema of the lips, erythema, urticaria, rash.

    From the genitourinary system: not often - erectile dysfunction.

    From the urinary system: not often - pollakiuria, polyuria, nocturia.

    From the immune system: not often - hypersensitivity to one of the components of the drug, Quincke's edema.

    From the side of metabolism: not often - hypertriglyceridemia.

    From the musculoskeletal system: not often - arthralgia.

    From the digestive system: not often - abdominal pain, nausea, constipation, dyspepsia, glossitis.

    On the part of the hematopoiesis system: not often - thrombocytopenia.

    From the respiratory system: often - cough; not often - dryness in the throat, pharyngeal and throat pain.

    From the cardiovascular system: often - "tides" of blood to the skin of the face; not often - a feeling of palpitations and tachycardia, a pronounced decrease in blood pressure, a circulatory collapse, a congestive cardiac failure.

    From the side of the hearing organ and labyrinthine disorders: often - vertigo, including positional vertigo.

    Laboratory indicators: not often - a decrease in the level of hemoglobin, an increase in ALT (alanine transferase) activity, ACT (asparagine transferase).

    Other: often - peripheral edema, not often - asthenia, increased fatigue, a feeling of heat.

    Enalaprooze

    From the central nervous system: very often - dizziness; often - headache; not often - paresthesia.

    From the side of the psyche: often - depression; not often - confusion, drowsiness, insomnia, nervousness; rarely - pathological dreams, sleep disturbance.

    From the skin: often - a rash; not often - increased sweating, itching, hives, alopecia; rarely - erythema multiforme, exfoliative dermatitis, Stevens-Jones syndrome, Lyell syndrome, pemphigus.

    From the urinary system: not often - renal insufficiency, proteinuria; rarely - oliguria.

    From the genitourinary system: not often - erectile dysfunction; rarely - gynecomastia.

    From the immune system: often - hypersensitivity, angioedema, swelling of the face, extremities, lips, tongue, glottis and / or larynx; rarely - autoimmune disorders.

    From the side of metabolism: not often - hypoglycemia, anorexia.

    From the musculoskeletal system: not often - muscle spasm.

    From the digestive system: very often - nausea; often - diarrhea, abdominal pain, impaired taste; infrequent - intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, dryness of the oral mucosa, stomach pain, stomach or duodenal ulcer; rarely - stomatitis, aphthous stomatitis, glossitis; very rarely - intestinal angioedema.

    From the liver and bile ducts: rarely - liver failure, hepatitis - cholestatic or necrotic, cholestasis.

    On the part of the hematopoiesis system: not often - anemia, including aplastic and hemolytic; rarely - thrombocytopenia, neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, insufficiency of bone marrow hematopoiesis.

    From the respiratory system: very often - cough; often shortness of breath; not often - rhinorrhea, pharyngeal-laryngeal pains, dysphonia, bronchospasm, asthma; rarely - lung infiltration, rhinitis, alveolar allergic / eosinophilic pneumonia.

    From the side of the organ of vision: very often - reduced visual acuity.

    From the side of the hearing organ and labyrinthine disorders: not often - ringing in the ears, vertigo.

    From the cardiovascular system: often - arrhythmia, angina pectoris, tachycardia, myocardial infarction, marked decrease in blood pressure, fainting, stroke, due to excessive lowering of blood pressure in patients with increased risk; not often - a feeling of palpitation, "hot flashes" of blood to the skin of the face, orthostatic hypotension; rarely - Raynaud's syndrome.

    Laboratory indicators: often - hyperkalemia,increase in creatinine in the blood; not often - an increase in urea in the blood, a decrease in the sodium content in the blood; rarely - an increase in the level of hemoglobin and hematocrit, an increase in the number of hepatic enzymes and a decrease in the concentration of bilirubin in the blood.

    Other: very often - asthenia; often - fatigue, chest pain; not often - malaise.

    A symptom complex including facial flushing, nausea, vomiting, and a marked decrease in blood pressure is also described and can develop with concomitant use of ACE inhibitors and a gold preparationsodium aurotomy malate) intravenously.

    Lercanidipine

    From the central nervous system: not often - dizziness, headache.

    From the side of the psyche: rarely - drowsiness.

    From the skin: rarely - a rash.

    From the immune system: very rarely - increased sensitivity.

    From the urinary system: rarely - polyuria.

    From the musculoskeletal system: rarely - myalgia.

    From the digestive system: rarely - nausea, dyspepsia, diarrhea, abdominal pain, vomiting.

    From the cardiovascular system: not often - tachycardia, palpitation, "hot flashes" of blood to the skin of the face; rarely - angina pectoris; very rarely - faint.

    Other: not often - peripheral edema; rarely - asthenia, increased fatigue.

    Overdose:

    There is no information about drug overdose. Presumably, in the case of an overdose, can cause conditions caused by an overdose of any of the active substances.

    Lercanidipine:

    Symptoms: peripheral vasodilation with pronounced lowering of blood pressure and reflex tachycardia, vomiting.

    Treatment: treatment is symptomatic, the choice of method of treatment depends on the degree of overdose and on the observed symptoms. Apply the following methods of medical care: gastric lavage, the intake of high doses of catecholamines, furosemide, cardiac glycosides and plasma substitutes, activated carbon, laxatives and intravenous dopamine. Also, to prevent the development of bradycardia, intravenous administration of atropine is possible.

    Enalapril:

    Symptoms: the main sign of an overdose is a marked decrease in blood pressure, which is accompanied by a blockade of the renin-angiotensin-aldosterone system and tetanus.Also, collapse, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

    Treatment: treatment is symptomatic. In severe cases, intravenous administration of a 0.9% solution of sodium chloride and, if possible, an infusion of angiotensin II and / or catecholamines is recommended. If the symptoms of an overdose develop immediately after taking the drug, then it is necessary to induce vomiting, to wash the stomach and take drugs from the group of adsorbents or sodium sulfate.

    Interaction:

    The antihypertensive effect of the drug can be potentiated with simultaneous use with other drugs with a similar effect, such as diuretics, beta-blockers, alpha-blockers and others. In addition, when combined, the following effects can be observed:

    Lercanidipine:

    The drug should not be taken in combination with inhibitors CYP3A4, such as ketoconazole, itraconazole, erythromycin and others, with cyclosporin and grapefruit juice (increase the concentration in the blood and lead to the potentiation of antihypertensiveeffect).

    Care should be taken when taking drugs with terfenadine, astemisole and III class of antiarrhythmic drugs (for example, amiodarone.) and quinidine. Simultaneous reception with anticonvulsants (for example, phenytoin, carbamazepine) and rifampicin can lead to a decrease in the antihypertensive effect of lercanidipine. Reception digoxin should be carefully monitored to identify clinical signs of digoxin toxicity.

    Taking the drug with midazolam leads to an increase in the absorption of lercanidipine in the gastrointestinal tract and a decrease in the rate of absorption. Metoprolol reduces the bioavailability of lercanidipine by 50%. Cimetidine in a dose of 800 mg per day does not lead to significant changes in the content and concentration of lercanidipine in the blood serum, but this combination requires special care, since with higher doses of cimetidine, the bioavailability of lercanidipine, and hence its antihypertensive effect, may increase. Fluoxetine has no effect on the pharmacokinetics of lercanidipine.In case of taking the drug with simvastatin, the drug should be taken in the morning, and simvastatin in the evening. Taking lercanidipine simultaneously with warfarin does not affect the pharmacokinetics of the latter.

    Enalapril:

    Simultaneous administration of the drug with potassium salts, with potassium-sparing diuretics (spironolactone, triamterene, eplerenone, amiloride), ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs, heparins (low molecular or unfractionated), cyclosporin, tacrolimus and trimethoprim increases the risk of hyperkalemia.

    It is not recommended to apply also together with lithium salts (if this combination is necessary, then carefully monitor the concentration of lithium in the blood plasma).

    Simultaneous reception with antidiabetic drugs (both oral and insulin) can cause the development of hypoglycemia in the first week of treatment. Diuretics ("loop" and thiazide) can cause a decrease in BCC and thus increase the risk of a marked decrease in blood pressure when treated with the drug. Long-term use nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the antihypertensive effect of ACE inhibitors. Both NSAIDs and ACE inhibitors (enalapril) contribute to an increase in potassium content in blood, which can lead to impaired renal function. Baclofen enhances the antihypertensive effect. Cyclosporin increases the risk of hyperkalemia. Ethanol enhances the antihypertensive effect of ACE inhibitors.

    Tricyclic antidepressants / antipsychotics / general anesthetics / narcotic analgesics may lead to a further decrease in blood pressure.

    Corticosteroids (except hydrocortisone as a replacement therapy for Addison's disease) reduce the antihypertensive effect (fluid retention followed by an increase in BCC). A joint application from other antihypertensive agents can enhance the antihypertensive effect of enalapril. Joint application with nitroglycerin and other nitrates and vasodilators leads to an even more pronounced decrease in blood pressure.

    Allopurinol, cytostatics, immunosuppressors, systemic corticosteroids and procainamide may lead to an increased risk of leukopenia.

    Antacids contribute to a decrease in the bioavailability of ACE inhibitors. Sympathomimetics can reduce the antihypertensive effect.

    Enalapril can be used concomitantly with acetylsalicylic acid (as an antiplatelet agent).

    When used simultaneously with the drug of gold (sodium aurotomy malate) intravenous development of side effects is possible.

    Special instructions:

    Particular attention in the treatment of hypertension requires patients:

    - with severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

    - with decompensated heart failure.

    Transient arterial hypotension is not a contraindication to the continuation of treatment, since after replenishment of bcc it is possible to expect an adequate response to taking the drug.

    Particular care should be taken in the initial stages of treatment of patients with mild to moderate renal failure. Patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney are particularly at risk of developing hypotension or renal failure due to the administration of ACE inhibitors. For this group of patients, treatment should be under the strict supervision of a physician,with a careful selection of the dose and the appointment of low doses of the drug. Before and during the treatment it is necessary to monitor the function of the kidneys.

    Particular care should be taken in the initial stages of treatment of patients with mild to moderate degree of liver function deficiency. If there is jaundice and a significant increase in the activity of "liver" enzymes, we urgently need to stop taking ACE inhibitors and consult a doctor.

    Due to the increased risk of anaphylactic reactions, the drug should not be administered to patients on hemodialysis using high-strength polyacrylonitrile membranes (AN69®), undergoing apheresis of low-density lipoproteins with dextran sulfate and immediately prior to the procedure of desensitization to aspen or bee venom.

    Like other ACE inhibitors, it has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races. Due to the use of enalapril, angioedema can develop in the face, limbs, tongue, throat or larynx. In this case, stop taking the medication immediately.Angioedema of the larynx can be lethal. Angioedema, swelling of the tongue, pharynx or larynx can lead to airway obstruction, epinephrine (0.3-0.5 ml epinephrine (adrenaline) solution subcutaneously in a ratio of 1: 1000) and maintain airway patency (incubation or tracheostomy). Among patients of the Negroid race receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of another race of belonging. Patients with an angioneurotic edema in a history not associated with the use of ACE inhibitors have an increased risk of developing angioedema while using any ACE inhibitor. Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors. During surgical interventions and / or general anesthesia in the use of agents that cause arterial hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin.If this results in a pronounced decrease in blood pressure, explained by a similar mechanism, it can be corrected by an increase in BCC.

    Hyperkalemia can develop on the background of therapy with ACE inhibitors, including enalapril. Risk factors for hyperkalemia are renal failure, advanced age, diabetes mellitus, some Concomitant conditions (decrease of BCC, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium or potassium-containing substitutes for common salt and the use of other drugs that increase the potassium content in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. Combined use of the above drugs should be done with caution. It is not recommended to drink alcohol during the period of therapy with the drug.

    There is evidence of reversible biochemical changes in the heads of spermatozoa with the use of calcium channel blockers, which can disrupt their ability to fertilize.

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

    It should be borne in mind the possibility of the appearance of weakness and drowsiness, so care must be taken when performing work requiring attention, especially at the beginning of treatment, with increasing doses of the drug and when driving vehicles.

    Form release / dosage:

    Tablets film-coated 10 mg + 10 mg, 10 mg + 20 mg.

    Packaging:

    By 7, 10, 14, 28, 30, 35, 42, 50 or 56 tablets in a blister of an opaque three-layer PA / Al / PVC film and aluminum foil.

    By 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters together with instructions for use in a cardboard bundle.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001184
    Date of registration:11.11.2011
    The owner of the registration certificate:RECORDATA Ireland Co., Ltd.RECORDATA Ireland Co., Ltd. Ireland
    Manufacturer: & nbsp
    Representation: & nbspRUSFIK LLC RUSFIK LLC Russia
    Information update date: & nbsp13.11.2015
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