Active substanceClopidogrelClopidogrel
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  • Dosage form: & nbspfilm-coated tablets
    Composition:

    1 tablet, film-coated, contains:

    active substance: Clopidogrel 75 mg (in the form of clopidogrel bisulfate);

    Excipients: cellulose powder, magnesium stearate, silicon dioxide colloid, croscarmellose sodium, microcrystalline cellulose;

    sheath: Opadray II YS-30-18056 white (ready-made shell mixture consisting of lactose, hypromellose, titanium dioxide and triacetin), dye Ponso red 4R; Opadry YS-1-7006 transparent (ready-made mixture for the shell, consisting of hypromellose and macrogol), saccharin sodium.

    The drug does not contain gluten.

    Description:

    Round pink biconvex tablets, covered with a film sheath.

    Pharmacotherapeutic group:antiplatelet agent
    ATX: & nbsp

    B.01.A. C.04   Clopidogrel

    Pharmacodynamics:

    Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to a platelet glycoprotein (GP) IIb/IIIa, acting as a receptor capable (in the activated state) of forming complementary bonds with proteins and factors involved in platelet aggregation. Clopidogrel irreversibly binds to ADP-receptors of platelet, depriving them of susceptibility to stimulation of ADP throughout the life-course. Clopidogrel also suppresses aggregation caused by other inducers, preventing their activation by liberated ADP, and does not affect the activity of phosphodiesterase.

    Reduction in the intensity of platelet aggregation is observed after 2 hours after a single dose of clopidogrel.The antiaggregant effect gradually increases, reaching a maximum on the 3-7th day of constant drug intake, while the level of aggregation inhibition is 40-60% (with a daily dose of 75 mg). After the drug is discontinued, the aggregation and bleeding time are restored at a rate corresponding to the rate at which new platelets enter the bloodstream (about 5 days).

    Clopidogrel has a high antithrombotic activity, prevents the development of atherothrombosis of vessels with atherosclerotic lesions, regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

    Pharmacokinetics:

    Clopidogrel is rapidly absorbed after repeated oral administration of the drug at a dose of 75 mg.

    Clopidogrel is a prodrug, it acquires antiaggregant properties due to transformation in the liver into an active thiol derivative, which quickly and irreversibly binds to platelet receptors, thus suppressing platelet aggregation. This metabolite is not detected in plasma. The main metabolite circulating in the blood - the carboxyl derivative of clopidogrel, does not affect the aggregation of platelets.Its peak plasma concentrations are reached about 1 hour after ingestion, and the half-life is about 8 hours. The kinetics of the main metabolite is linear in the dose range of 50 to 150 mg. Clopidogrel and its main metabolite reversibly bind to plasma proteins (98% and 94%, respectively).

    Food does not significantly affect the bioavailability of the drug. About 50% of the drug is excreted by the kidneys, 46% - with feces (within 5 days after admission). In both plasma and urine, a glucuronide derivative of the basic inactive metabolite of clopidogrel is found.

    Indications:

    Prophylaxis of ischemic disorders (myocardial infarction, stroke, peripheral arterial thrombosis, sudden vascular death) in patients with atherosclerosis including:

    - after a recent myocardial infarction, ischemic stroke;

    - against the background of recently diagnosed peripheral arterial diseases;

    - with acute coronary syndrome without segment elevation ST (unstable angina or myocardial infarction without the formation of a pathological wave Q na ECG) in combination with acetylsalicylic acid.

    Contraindications:

    - Hypersensitivity to any components of the drug;

    severe hepatic impairment;

    - Acute bleeding (eg, peptic ulcer, with intracranial hemorrhage);

    - Pregnancy and lactation;

    - age to 18 years (safety of application not established).

    Carefully:

    Clopidogrel, like other antiplatelet agents, should be used with caution in patients with:

    - liver and kidney disease (moderate hepatic and / or renal failure);

    - injuries;

    - preoperative states;

    - simultaneous administration of acetylsalicylic acid, NSAIDs (including COX-2 inhibitors), heparin and glycoprotein inhibitors IIb/IIIa.

    Pregnancy and lactation:In experiments on animals it was shown that clopidogrel and its metabolites penetrate into breast milk, do not affect fertility and do not have toxic effects on the fetus. However, in the absence of sufficient safety data, it is not recommended to use the drug in pregnant and lactating women.
    Dosing and Administration:

    Adults and Seniors

    The dosage of the drug depends on the medical criteria and the condition of the patient.Usually the recommended dose is 75 mg (1 tablet) orally 1 time per day regardless of food intake.

    Treatment should be started in the period from several days to 35 days in patients after myocardial infarction (Q-former) and from 7 days to 6 months - in patients after ischemic stroke.

    In patients with acute coronary syndrome without segment elevation ST (unstable angina or myocardial infarction without a tooth Q) treatment with clopidogrel should be started with a single dose of 300 mg, and then continued with a dose of 75 mg per day in combination with acetylsalicylic acid.

    Side effects:

    When taking therapeutic doses of the drug, it is usually well tolerated. The main side effects of clopidogrel are as follows.

    Hemostasis: gastrointestinal bleeding, hematoma, hematuria, hemorrhage in the conjunctiva. Very rarely there was intracranial hemorrhage, hemarthrosis, hemoptysis, hematuria, retroperitoneal, intraocular or pulmonary hemorrhage / bleeding.

    On the part of the hematopoiesis system: in clinical studies, extremely marked neutropenia, anemia, thrombocytopenia, granulocytopenia, agranulocytosis, and leukopenia were extremely rare.

    On the part of the digestive system: sometimes there may be abdominal pain, indigestion (constipation, diarrhea, nausea), gastritis; in rare cases - vomiting, peptic ulcer of the stomach and duodenum; very rarely - colitis, pancreatitis.

    From the side of the liver: very rarely - hepatitis, steatosis.

    Kidney and urinary system: very rarely - glomerulonephritis, cystitis.

    From the cardiovascular system: In rare cases, edema, heart failure, arterial hypertension can be observed.

    Skin and allergic reactions: skin rashes and itching. Very rarely there were urticaria, pruritis, eczema, erythematous rash, bullous rash, maculopapular rash, angioedema, anaphylactoid reactions.

    From the musculoskeletal system: very rarely - arthralgia, arthritis.

    From the respiratory system: very rarely - bronchospasm.

    From the nervous system: In rare cases, headache, dizziness, neuralgia, vertigo, hyperesthesia, paresthesia are possible.

    From the side of psychiatry: very rarely - irritability, confusion, hallucinations.

    Lab tests: very rarely - a change in the activity of hepatic transaminases, an increase in the creatinine of the blood.

    Other: very rarely - vasculitis, fever.

    Overdose:

    With a single oral dose of 1050 mg clopidogrel (14 tablets of 75 mg), no adverse events and the need for special therapeutic measures were noted.

    With a single oral dose of 600 mg clopidogrel (8 tablets of 75 mg) by healthy volunteers, no side effects were noted. The increase in bleeding time corresponded to the value recorded after taking a therapeutic dose (75 mg / day).

    If it is necessary to quickly correct the increased bleeding time, a transfusion of platelet mass is recommended.

    The specific antidote is not known.

    Interaction:Acetylsalicylic acid: does not significantly change the effect of clopidogrel on platelets. Clopidogrel potentiates the effect of acetylsalicylic acid on platelet aggregation, induced by collagen.

    NSAIDs: the appointment with clopidogrel requires caution (increased risk of bleeding).

    Warfarin: the safety of simultaneous use with clopidogrel is not established.

    Heparin: there was no interaction of both drugs in healthy volunteers.However, the safety of the combination is not established.

    Other drugs

    Clopidogrel was used concomitantly with cimetidine, phenobarbital, estrogens, atenolol, nifedipine (combination atenolol + nifedipine) without pronounced interaction.

    No effect on pharmacokinetics theophylline and digoxin.

    When conducting clinical trials clopidogrel was used with the following drugs without pronounced interaction: calcium antagonists, beta-blockers, diuretics, cholesterol-lowering drugs, coronary vasodilators, hypoglycemic drugs, angiotensin-converting enzyme inhibitors, antiepileptic drugs, antacid agents, hormone replacement therapy.

    In the study in vitro Clopidogrel suppressed P450, thus it can be assumed that, when used simultaneously with tamoxifen, tolbutamide, warfarin, phenytoin, fluvastatin, and many NSAIDs possibly impact on their metabolism in the body.

    Special instructions:

    During the period of treatment, it is necessary to monitor the parameters of the hemostasis system (platelet count, platelet function tests), to regularly investigate the functional activity of the liver.

    A general blood test should be monitored during the first week of treatment with clopidogrel in combination with acetylsalicylic acid, NSAIDs, heparin, glycoprotein inhibitors IIb/IIIor fibrinolytic, as well as in patients with an increased risk of bleeding (trauma, surgery or other pathological conditions).

    The drug lengthens the time it takes to stop bleeding. This should be considered for patients who are undergoing surgery (including in dentistry).

    In the case of surgical interventions, if the antiaggregant effect is undesirable, the drug should be discontinued 7 days before the operation.

    Patients should inform the doctor about each case of unusual bleeding.

    Be wary appoint patients with severe violations of the liver due to the risk of hemorrhagic diathesis, as well as patients receiving drugs that can induce bleeding (acetylsalicylic acid and other NSAIDs).

    Due to insufficient data on the use of clopidogrel in patients with acute Q-basic myocardial infarction, clopidogrel treatment should not be started within the first few days after a heart attack.

    Due to insufficient data, do not assign clopidogrel in the acute period of ischemic stroke (the first 7 days).

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

    Symptoms of clopidogrel influence on intellectual and psychomotor functions and abilities were not revealed.

    Form release / dosage:

    Tablets coated with a film coating, 75 mg.

    Packaging:

    For 14 tablets in a blister of aluminum foil-film PVC / polyamide / aluminum.

    For 1 or 2 blisters together with instructions for use are placed in a cardboard box.

    Storage conditions:

    In dry, dark place 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 expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008638/08
    Date of registration:30.10.2008
    The owner of the registration certificate:Kimika Montpellier, SA, Bago Group CompanyKimika Montpellier, SA, Bago Group Company Argentina
    Manufacturer: & nbsp
    Representation: & nbspBBC FARMA BV BBC FARMA BV Netherlands
    Information update date: & nbsp07.08.2015
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