Index of drugs

Prophylaxis of thrombotic complications in atherosclerosis. Clopidogrel is indicated 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. Adult patients with acute coronary syndrome: without ST segment elevation (unstable angina or non-Q-wave myocardial infarction), including patients who receive a stent during percutaneous coronary intervention in combination with Acetylsalicylic acid (ASA), with acute coronary angioplasty ST segment elevation myocardial infarction, in combination with ASA, in patients conservatively treated eligible for thrombolytic therapy.Prevention of clots and congestion in patients with atrial fibrillation. Clopidogrel with acetylsalicylic acid is indicated for use in adult patients with atrial fibrillation who can not be given vitamin K antagonists and who have a low risk of bleeding. It is administered to prevent blood clots and congestion, including stroke.

1 tabl powl. contains 75 mg of clopidogrel (as hydrogen sulphate). The preparation contains lactose and hydrogenated 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 P2Y platelet receptor₁₂ and further activation of the GPIIb / IIIa glycoprotein complex mediated by ADP, resulting in inhibition of platelet aggregation. Clopidogrel also inhibits platelet aggregation induced by other agonists than ADP by blocking the enhanced platelet activation by the released ADP. 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 per 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. At least 50% of the dose is absorbed. It binds 98% of plasma proteins and 94% of the main metabolite. It is extensively metabolised in the liver. Metabolism is mediated through two major metabolic pathways: esterase is the first to take part, hydrolyzing clopidogrel to an inactive carboxylic acid derivative (it accounts for 85% of circulating metabolites), while the other is mediated by numerous cytochrome P450 isoenzymes. Initially, clopidogrel is metabolized to the 2-oxoclopidogrel intermediate metabolite, which is then converted into the active metabolite, a thiol derivative. The thiol metabolite binds rapidly and irreversibly to platelet receptors, inhibiting their aggregation. The process is regulated by the CYP3A4, CYP2C19, CYP1A2 and CYP2B6 isoenzymes. Approximately 50% of the drug is excreted in the urine and about 46% in the faeces. T_0,5 the main circulating metabolite is 8 hours.

Hypersensitivity to the active substance or to any of the excipients. Severe hepatic impairment. Active pathological bleeding, such as a peptic ulcer or intracranial haemorrhage.

Due to the risk of bleeding and hematological side effects, blood counts and / or other appropriate tests should be considered immediately as soon as clinical signs suggestive of bleeding appear during treatment. Caution should be exercised when using clopidogrel in patients who may be at greater risk of major bleeding due to trauma, surgery or other pathological conditions, and in patients receiving ASA, Heparin, glycoprotein IIb / IIIa inhibitors or NSAIDs, including COX-2 inhibitors. 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.The concomitant use of clopidogrel and oral anticoagulants is not recommended as it may increase the intensity of bleeding. If the patient is scheduled for surgery and the antiplatelet effect is temporarily undesirable, clopidogrel should be discontinued 7 days before the surgery. Patients should inform physicians and dentists that they are taking clopidogrel before planning any surgery and before using any new medicine. Clopidogrel should be used with caution in patients with pathological changes predisposing to bleeding (especially from the gastrointestinal tract and intraocular). Patients should be advised that stopping bleeding may take longer than usual if they are taking clopidogrel (also with acetylsalicylic acid) and that they should inform the doctor about any unusual bleeding (location and duration). Very rarely, thrombotic thrombocytopenia (TTP) has been reported after treatment with Clopidogrel, sometimes after a short exposure. It is characterized by the occurrence of thrombocytopenia and microangiopathic hemolytic anemia, combined with either neurological changes, or with renal dysfunction or with fever. TTP is a potentially lethal condition requiring immediate treatment, including plasmapheresis. Due to the lack of data, the use of clopidogrel is not recommended during the first 7 days after acute ischemic stroke. In patients with poor CYP2C19 enzyme metabolism, clopidogrel, when administered at the recommended doses, produces a less active metabolite of clopidogrel and has a weaker effect on platelet function. There are tests that determine the patient's CYP2C19 genotype. Co-administration of clopidogrel and potent and moderate CYP2C19 inhibitors is not recommended. The therapeutic experience in the use of clopidogrel in patients with impaired renal function is limited - caution should be exercised when using clopidogrel in these patients. Experience in patients with moderate hepatic disease who may be prone to bleeding is limited - clopidogrel should be used with caution in this population. Clopidogrel should not be used in children due to doubts about its effectiveness. The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose. The product contains hydrogenated castor oil, which can cause indigestion and diarrhea.

Due to the lack of data on the use of clopidogrel in pregnant women, it is recommended to avoid the use during pregnancy in order to be cautious. It is not known whether clopidogrel / metabolites are excreted in human milk. Breast-feeding should be discontinued during treatment.

Common: hematoma, nosebleed, gastrointestinal haemorrhage, diarrhea, abdominal pain, indigestion, bruising, bleeding at the points of the prick. Uncommon: thrombocytopenia, leukopenia, eosinophilia, intracranial bleeding (some of the reported cases were fatal), headache, paresthesia, dizziness, eye bleeding (conjunctival, intraocular, retinal), stomach and duodenal ulcer, gastritis, vomiting , nausea, constipation, flatulence, rash, pruritus, bleeding within the skin (purpura), haematuria, prolonged bleeding time, decreased neutrophil count, decreased platelet count. Rare: neutropenia (including severe neutropenia), vertigo-derived dizziness, retroperitoneal haemorrhage. Very rare: thrombotic thrombocytopenic purpura (TTP), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, severe granulocytopenia, anemia, serum sickness, alleged anaphylactic reactions, hallucinations, confusion, taste disturbances, severe haemorrhage, postoperative hemorrhage, angiogenesis , hypotension, bleeding from the airways (haemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonitis, gastrointestinal and retroperitoneal haemorrhage, pancreatitis, colitis (including ulcerative or lymphocytic colitis), inflammation of the membrane mucous oral cavity, acute hepatic failure, hepatitis, abnormal liver function tests, bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), angioneurotic edema, erythematous rash, urticaria, eczema , lichen planus, bleeding in the musculoskeletal system (arthritis), arthritis, arthralgia, muscle pain, glomerulonephritis, increased blood creatinine, fever.

Orally.Adults and elderly patients: 75 mg in a single daily dose. In patients with acute coronary syndrome: without ST 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 daily (with acetylsalicylic acid (ASA) 75 mg to 325 mg daily). Because higher doses of ASA were associated with a higher 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; with ST-segment elevation myocardial infarction: clopidogrel should be started with a loading dose of 300 mg, followed by 75 mg once a day in combination with ASA and with or without thrombolytics. In patients over 75 years of age, 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 should be prescribed a single dose of 75 mg clopidogrel. Then start 75-100 mg / day ASA in combination with clopidogrel. If you forget to take a dose: within 12 hours of the time it is taken to take your dose: the patient should take the missed dose as soon as possible and take the Next dose within the prescribed time; after 12 hours: the patient should take the next dose within the prescribed time and not take a double dose. The medicine can be taken with or without food.