Pharm group: antiplatelet drug.
Formdata: Antiplatelet drug. Selectively reduces the binding of ADP receptors on platelets and activation of the receptor glycoprotein IIb/IIIa by the action of ATP, thus disrupting platelet aggregation.
Reduces agregatia platelets, caused by other agonists, preventing activation of the released ADP, does not affect the activity of PDE. Irreversibly binds to ADP-receptors platelets, which remain impervious to the stimulation of ADP throughout the life cycle (about 7 days).
Inhibition of platelet aggregation observed after 2 h after administration (40% inhibition) initial dose of 400 mg. the Maximum effect (60% suppression of aggregation) develops after 4-7 days of admission in a dose of 50-100 mg/day. Antiplatelet effect lasts for the entire period of life of platelets (7-10 days).
Pharmacokinetics: Absorption and bioavailability of high concentration in the plasma is low and through 2 hours after admission does not reach the limit of measurement (0.025 µg/l). Connection with plasma proteins – 98-94%.
Is a prodrug. Metabolized in the liver. The active metabolite in the blood is undetectable. Define the main metabolite – inactive derivative carboxylato acid, which TCmax after repeated oral doses of 75 mg achieved through 1 h (Cmax about 3 mg/l).
Excretion: kidney – 50%, through the intestines – 46% (during 120 h after injection). T1/2 the main metabolite after single and repeated administration – 8 h. the concentration of secreted metabolites by the kidneys – 50%.
The concentration of the main metabolite in plasma after administration of 75 mg/day lower in patients with severe renal failure (QC 5-15 ml/min) compared with chronic renal failure of moderate severity (QC 30-60 ml/min) and healthy subjects.
Indications: Prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion.
In combination with ASA for the prevention of thrombotic complications in acute coronary syndrome: ST-segment elevation when possible, use of thrombolysis, without ST-segment elevation (unstable angina, myocardial infarction without Q wave), including patients undergoing stenting.
Contraindications: Hypersensitivity, severe liver failure, acute bleeding (including bleeding from peptic ulcer or intracranial hemorrhage), pregnancy and lactation, children up to age 18 years.
For LF, contain lactose (advanced): lactose intolerance, lactase deficiency syndrome glucose-galactose malabsorption.
With caution. Moderate hepatic insufficiency, chronic renal failure, pathological conditions that increase the risk of bleeding (including trauma, surgery), bleeding tendency, concomitant use of ASA, warfarin, NSAIDs (including COX-2 inhibitors), heparin, and inhibitors of glycoprotein IIb/IIIa, an inherited decrease in the function of isoenzyme СУР2С19.
Dosing: Inside, regardless of meals.
For prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion – 75 mg 1 time per day.
In patients with myocardial infarction, the treatment can begin from the first day to 35 th day of myocardial infarction, and in patients with ischemic stroke within 7 days to 6 months after ischemic stroke.
For the prevention of thrombotic complications in acute coronary syndrome without ST-segment elevation (unstable angina, myocardial infarction without tooth Q) – start with a single oral loading dose of 300 mg, then the dose is 75 mg/day (in combination with ASA in doses of 75-325 mg/day, the recommended dose is 100 mg/day). Maximum beneficial effect after 3 months. The course of treatment up to 1 year.
To prevent thrombotic complications of acute coronary syndrome with ST-segment elevation (acute myocardial infarction with ST-segment elevation) – 75 mg/day with an initial one-time admission loading dose in combination with ASA and with thrombolytic drugs (or without thrombolytics).
Combination therapy is started as early as possible after the onset of symptoms and continued for at least 4 weeks. In patients older than 75 years, treatment with clopidogrel should be started without taking a loading dose.
In patients with a genetically determined reduced function of the CYP2C19 isoenzyme may reduce the effect of clopidogrel. The optimum dosage regimen in such patients is not installed.
Experience of use in patients with chronic renal failure or moderate hepatic insufficiency is limited.
Side effects: Frequency: very often – more than 1/10, often more 1/100 and less 1/10, uncommon – more 1/1000 and less 1/100, seldom more 1/10000 and less 1/1000, very rare – less than 1/10000, including isolated cases.
Organs of hematopoiesis: rarely – thrombocytopenia, leukopenia, eosinophilia, rarely – naturopatia, including severe, very rarely thrombotic thrombocytopenic purpura, anemia including aplastic, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia.
Allergic reactions: very rarely – anaphylactic reactions, serum sickness.
From the nervous system: rare – headache, dizziness, paresthesia, intracranial hemorrhage, including fatalities, rarely – confusion, hallucinations, taste disturbance.
From the sensory organs: rarely – bleeding in the conjunctiva, the eye, the retina, and rarely vertigo.
From the CCC: often – swelling, very rarely – heavy bleeding, bleeding from the operative wound, vasculitis, decrease in blood pressure.
The respiratory system: often – nasal bleeding; very rarely bronchospasm, interstitial pneumonitis, pulmonary hemorrhage, hemoptysis.
From the digestive system: often – diarrhea, abdominal pain, dyspepsia, bleeding from the digestive tract, rarely, gastric ulcer and 12 duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence rare retroperitoneal bleeding, very rarely – pancreatitis, colitis, including ulcerative or lymphocytic, stomatitis, acute liver failure, hepatitis, disturbance in liver function tests, bleeding from the gastrointestinal tract with a fatal outcome.
With the skin: often – bruising, rarely – skin rash, pruritus, purpura; very rarely angioedema, urticaria, rash erythematous, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, eczema, lichen planus.
From the side of musculoskeletal system: very rarely – hemarthrosis, arthritis, arthralgia, myalgia.
From the urogenital system: rarely – hematuria, very rarely – glomerulonephritis, gipercreatininemia.
Local reactions: often – bleeding at the injection site.
Laboratory parameters: rare – prolonged bleeding time.
Other: very rarely – fever.
Overdose: Symptoms: prolonged bleeding time, bleeding complications.
Treatment: stop bleeding, platelet transfusion.
Interaction: Simultaneous reception of warfarin with clopidogrel can increase the intensity of bleeding, therefore, the use of this combination is not recommended.
The appointment of inhibitors of glycoprotein IIb/IIIa, ASA, heparin in conjunction with clopidogrel increases the risk of bleeding.
While the use of NSAIDs may increase the risk of bleeding.
Simultaneous treatment with inhibitors of CYP2C19 (e.g., omeprazole) is not recommended.
Clopidogrel active metabolite inhibits the activity of the isoenzyme CYP2C9, resulting in increase concentration of phenytoin, tolbutamide and the NSAIDs in plasma.
Special instructions: In case of surgery if antiplatelet effect is undesirable, the treatment should be discontinued 7 days before surgery.
Patients should be warned that because the stop occurs on a background of the drug bleeding requires more time, they should inform the doctor about each case, unusual bleeding. Patients should also inform the doctor about the drug if they have surgery (including dental surgery) or if your doctor prescribes a new patient drugs.
During treatment necessary to monitor the hemostatic parameters (APTT, the number of platelets, tests of functional activity of platelets), regularly examine the functional activity of the liver.
In severe liver dysfunction should be aware of the risk of developing a hemorrhagic diathesis.
It is not recommended to appoint patients with ischemic stroke of less than 7 days old.
LF, containing gidrogenizirovannoe castore oil can cause dyspepsia and diarrhea.
Very rarely in patients receiving clopidogrel developed thrombotic thrombocytopenic purpura, sometimes after short-term use. The condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia associated with neurological disorders, kidney damage and fever. Thrombotic thrombocytopenic purpura is a potentially life-threatening condition that requires immediate treatment, including plasmapheresis.
|The purpose of the medication||Anti-aggregants|