Index of drugs

Prophylaxis of thrombotic complications in atherosclerosis: in adult patients with myocardial infarction (from several days to less than 35 days), with ischemic stroke (from 7 days to less than 6 months) and with diagnosed peripheral artery disease; in adult patients with non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction) including patients who receive a stent during percutaneous coronary intervention in combination with Acetylsalicylic acid or acute myocardial infarction with ST elevation, in combination with Acetylsalicylic acid, in patients conservatively treated eligible for thrombolytic therapy.Prophylaxis of thrombotic complications in atherosclerosis and thromboembolism (including stroke) in atrial fibrillation: in adult patients with atrial fibrillation and at least one risk factor for vascular complications where treatment with vitamin K antagonists can not be used and the risk of bleeding is low in combination with acetylsalicylic acid.

1 tabl powl. contains 75 mg of Clopidogrel in the form of bisulphate; drug contains lactose and castor oil.

Platelet aggregation inhibitor. Clopidogrel is a prodrug and one of its active metabolites inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of ADP to its platelet receptor and further activation of ADP-mediated GP IIb / IIIa complex, leading to inhibition of platelet aggregation. It also inhibits platelet aggregation induced by other agonists, blocking the potentiation of platelet activation by the released ADP. It works by irreversibly modifying the platelet ADP receptor. Repeated doses of 75 mg daily cause a significant inhibition of ADP-induced platelet aggregation, which gradually increases and reaches a state of equilibrium between Day 3 and Day 7. At steady-state, the mean inhibition level observed at 75 mg / day was 40- 60%. Platelet aggregation and bleeding time gradually return to baseline, usually within 5 days after discontinuation of treatment. Clopidogrel is rapidly absorbed from the digestive tract. About 50% of the dose is absorbed. It is extensively metabolised in the liver. Metabolism takes place through two major metabolic pathways. In the first part, esterases take part by hydrolysing clopidogrel to an inactive carboxylic acid derivative (constituting 85% of circulating metabolites); the second is mediated by numerous cytochrome P450 isoenzymes: initially, clopidogrel is metabolized to the intermediate (2-oxoclopidogrel) metabolite, which is then converted into the active metabolite, a thiol derivative. This process is regulated by the CYP3A4, CYP2C19, CYP1A2 and CYP2B6 isoenzymes. The active thiol metabolite binds rapidly and irreversibly to platelet receptors, inhibiting their aggregation. About 50% of the drug is excreted in the urine and about 46% in the faeces. T_0,5 clopidogrel is 6 hours.

Hypersensitivity to the active substance or any of the excipients. Severe liver dysfunction. Active pathological bleeding (eg peptic ulcer, intracranial haemorrhage).

Patients should be closely monitored for any signs of bleeding, including occult bleeding, especially during the first weeks of treatment and / or after invasive cardiac surgery or after surgery. Because of the risk of bleeding and haematological adverse reactions, blood counts should be immediately considered and / or other appropriate tests should be considered for clinical signs suggestive of bleeding during treatment. Caution should be exercised in patients who may be at greater risk of major bleeding due to injury, surgery or other pathological conditions, in patients with bleeding episodes (especially gastrointestinal and intraocular) lesions, and in patients receiving acetylsalicylic acid, NSAIDs, Heparin or IIb / IIIa glycoprotein inhibitors, including COX-2 inhibitors and selective serotonin reuptake inhibitors (SSRIs).Co-administration of clopidogrel with oral anticoagulants is not recommended. If the patient is to undergo elective surgery and the antiplatelet effect is temporarily undesirable, clopidogrel should be discontinued 7 days before the procedure. Clopidogrel is not recommended for the first 7 days after acute ischemic stroke. Very rarely, thrombotic thrombocytopenia (TTP) has been reported after treatment with Clopidogrel, sometimes after a short exposure - TTP is a potentially fatal condition requiring immediate treatment, including plasmapheresis. Cases of acquired haemophilia have been reported following treatment with clopidogrel - in the case of confirmation of an isolated prolongation of partial thromboplastin time after activation (APTT) with bleeding or without bleeding, the possibility of acquired haemophilia should be considered; patients with a confirmed diagnosis of acquired haemophilia should be subjected to specialist medical care and treatment with clopidogrel should be discontinued. Use with caution in patients with impaired renal function or with moderate hepatic disease. Due to the possibility of hypersensitivity reactions (rash, angioneurotic edema) and haematological toxicity (thrombocytopenia, neutropenia) in patients using thienopyridines (clopidogrel, ticlopidine, prasugrel) an increased risk of side effects of other thienopyridines may occur. An interview should be made for hypersensitivity to other thienopyridines. The use of CYP2C19 inhibitors concomitantly with clopidogrel is not recommended, as this combination therapy may reduce the concentration of the active metabolite of clopidogrel. In patients with genetically determined poor CYP2C19 activity, there is less exposure to the active metabolite of clopidogrel and weaker suppression of platelet aggregation (tests to determine the patient's CYP2C19 genotype are available). Clopidogrel should not be used in children due to doubts about its effectiveness. Due to the lactose content, the preparation should not be used in patients with hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. Due to the content of hydrogenated castor oil, the drug may cause indigestion and diarrhea.

The use of the drug during pregnancy is not recommended. You should not breast-feed during treatment with clopidogrel.

Common: hematoma, nosebleed, gastrointestinal haemorrhage, diarrhea, abdominal pain, indigestion, bruise, bleeding at the injection site. Uncommon: thrombocytopenia, leukopenia, eosinophilia, intracranial bleeding (some fatal cases), headache, paresthesia, central dizziness, eye bleeds (conjunctival, intraocular, retinal), gastric and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence, rash, itching, purpura, haematuria, prolonged bleeding time, decreased neutrophil count, decreased platelet count. Rare: neutropenia (also severe), vertigo, retroperitoneal haemorrhage, gynecomastia. Very rare: thrombotic thrombocytopenic purpura (TTP), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, acquired hemophilia A, granulocytopenia, anemia, serum sickness, anaphylactoid reactions, hallucinations, confusion, taste disturbances, severe haemorrhage, surgical haemorrhage, inflammation blood vessels, hypotension, bleeding from the airways (haemoptysis, pulmonary haemorrhage), bronchospasm, interstitial pneumonitis, eosinophilic pneumonia, gastrointestinal haemorrhage and retroperitoneal death, pancreatitis, colitis (including ulcerative and lymphocytic), inflammation oral mucosa, acute hepatic failure, hepatitis, abnormal liver function tests, bladder dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), acute generalized pustular exanthema (AGEP), angioedema nodular, drug-induced hypersensitivity syndrome, drug-induced erosion with eosinophilia and systemic symptoms (DRESS), erythematous rash, urticaria, eczema, lichen planus, bleeding within the musculoskeletal system (intraarticular haemorrhage), arthritis, joint and muscle pain, glomerulonephritis, increase in blood creatinine, fever.Not known: hypersensitivity reactions among thienopyridines (such as ticlopidine, prasugrel).

Orally. Adults and the elderly: 75 mg once daily, with or without food.Patients with acute coronary syndrome without ST segment elevation (unstable angina or non-Q-wave myocardial infarction): clopidogrel should be started with a single 300 mg loading dose and then continued with 75 mg once a day (with ASA 75-325 mg daily). Because higher doses of acetylsalicylic acid have been associated with a greater risk of bleeding, it is recommended that the dose of ASA should not exceed 100 mg. The optimal duration of treatment has not been clearly established. Data from clinical trials confirm the use up to 12 months, and the maximum beneficial effect was observed after 3 months.Patients with acute coronary syndrome with acute myocardial infarction with ST elevation: Clopidogrel should be started with a 300 mg loading dose followed by 75 mg once daily in combination with acetylsalicylic acid and thrombolytics or no thrombolytic agents. In patients> 75 years, clopidogrel should be started without a loading dose. Combination therapy should be started as soon as possible after onset of symptoms and continued for at least 4 weeks. The benefit of co-administration of clopidogrel with ASA beyond 4 weeks has not been studied in this treatment model.Patients with atrial fibrillation: clopidogrel should be given as a single daily dose of 75 mg. At the same time, ASA (75-100 mg daily) should be started and continued.Skip the dose: before the expiry of 12 hours from the prescribed time of taking the dose - immediately take the missed dose and take the Next dose within the prescribed time; after 12 h - take the next dose within the prescribed time and do not take a double dose.