Clopidogrel tablets p / o 75mg, No. 28

• Prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion. In combination with acetylsalicylic acid for the prevention of thrombotic complications in acute coronary syndrome: with ST segment elevation if thrombolytic therapy is possible; without ST segment elevation (unstable angina pectoris, myocardial infarction without Q wave), incl. in patients undergoing stenting.

• Prevention of thrombotic and thromboembolic complications, including stroke, with atrial fibrillation (atrial fibrillation) in the presence of at least one risk factor for the development of vascular complications, the inability to take indirect anticoagulants and the presence of a low risk of bleeding (in combination with acetylsalicylic acid).

It is taken orally 1 time / day. The initial and maintenance dose is 75 mg / day. Loading dose - 300 mg / day The scheme of application depends on the indications and the clinical situation.

1 tab.

clopidogrel hydrogen sulfate 97.87 mg,

which corresponds to the content of clopidogrel 75 mg

• Acute bleeding (including with a peptic ulcer or intracranial hemorrhage),

• severe liver failure

• pregnancy,

• lactation period (breastfeeding),

• children and adolescents up to 18 years old,

• hypersensitivity to clopidogrel.

pharmachologic effect

An inhibitor of platelet aggregation. Selectively inhibits the binding of adenosine diphosphate (ADP) to platelet receptors and the activation of the GPIIb / IIIa complex, thus inhibiting platelet aggregation. It also inhibits platelet aggregation caused by other agonists by blocking the increase in platelet activity by released ADP. Does not affect PDE activity. Clopidogrel irreversibly alters the ADP receptors on platelets, so platelets remain dysfunctional throughout their 'life', and normal function is restored as they renew (after about 7 days).

Pharmacokinetics

After oral administration in a dose of 75 mg, clopidogrel is rapidly absorbed from the gastrointestinal tract. However, the concentration in blood plasma increases slightly and, 2 hours after administration, does not reach a measurable level (0.025 ?g / L). It is extensively metabolized in the liver. The main metabolite is an inactive derivative of carboxylic acid and accounts for about 85% of the parent substance circulating in plasma. The Cmax of this metabolite in blood plasma after repeated doses of clopidogrel is about 3 mg / l and is observed approximately 1 hour after administration. The pharmacokinetics of the main metabolite is characterized by a linear relationship in the dose range of clopidogrel 50-150 mg. Clopidogrel and the main metabolite irreversibly bind to plasma proteins in vitro (98% and 94%, respectively). This relationship remains unsaturated in vitro over a wide concentration range.After oral administration of 14C-labeled clopidogrel, about 50% of the dose taken is excreted in the urine and approximately 46% in the feces within 120 hours. T1 / 2 of the main metabolite is 8 hours. Compared with healthy young volunteers, the plasma concentration of the main metabolite is significantly higher in elderly patients (aged 75 years and older), while there are no changes in platelet aggregation and bleeding time. In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.T1 / 2 of the main metabolite is 8 hours. Compared with healthy young volunteers, the plasma concentration of the main metabolite is significantly higher in elderly patients (aged 75 years and older), while there are no changes in platelet aggregation and bleeding time. In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.T1 / 2 of the main metabolite is 8 hours. Compared with healthy young volunteers, the plasma concentration of the main metabolite is significantly higher in elderly patients (aged 75 years and older), while there are no changes in platelet aggregation and bleeding time. In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.Compared with healthy young volunteers, the plasma concentration of the main metabolite is significantly higher in elderly patients (aged 75 years and older), while there are no changes in platelet aggregation and bleeding time. In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.Compared with healthy young volunteers, the plasma concentration of the main metabolite is significantly higher in elderly patients (aged 75 and older), while there are no changes in platelet aggregation and bleeding time. In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.In severe kidney disease (CC 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in moderate kidney disease (CC 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.

Side effect

From the side of the blood coagulation system: often - bleeding; infrequently - an increase in bleeding time. From the digestive system: very often - gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia; infrequently - stomach and duodenal ulcers, vomiting, nausea, constipation, bloating; rarely - retroperitoneal hemorrhage; very rarely - fatal gastrointestinal bleeding and retroperitoneal hemorrhage, pancreatitis, colitis (including ulcerative colitis or lymphocytic colitis), stomatitis, acute liver failure, hepatitis, abnormal liver function indicators. From the hematopoietic system: infrequently - thrombocytopenia, leukopenia, eosinophilia; rarely, neutropenia, including severe neutropenia; very rarely - thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia,agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia. From the nervous system: infrequently - intracranial hemorrhage (several fatal cases have been reported), headache, paresthesia, dizziness; very rarely - disturbances in taste, hallucinations, confusion. From the senses: infrequently - eye hemorrhages (conjunctival, in the tissue and retina of the eye); rarely, vertigo. From the side of the cardiovascular system: very rarely - vasculitis, lowering blood pressure. From the respiratory system: often - epistaxis; very rarely - bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonia. From the immune system: very rarely - serum sickness, anaphylactoid reactions. On the part of the skin and subcutaneous tissues:often - subcutaneous bruising; infrequently - rash, itching, purpura (subcutaneous hemorrhage); very rarely - bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) angioedema, erythematous rash, urticaria, eczema, lichen planus. From the musculoskeletal system: very rarely - hemorrhages in muscles and joints, arthritis, arthralgia, myalgia. From the urinary system: infrequently - hematuria; very rarely - glomerulonephritis, an increase in the concentration of creatine in the blood. Others: often - bleeding from the puncture site of the vessels; very rarely - fever.eczema, lichen planus. From the musculoskeletal system: very rarely - hemorrhages in muscles and joints, arthritis, arthralgia, myalgia. From the urinary system: infrequently - hematuria; very rarely - glomerulonephritis, an increase in the concentration of creatine in the blood. Others: often - bleeding from the puncture site of the vessels; very rarely - fever.eczema, lichen planus. From the musculoskeletal system: very rarely - hemorrhages in muscles and joints, arthritis, arthralgia, myalgia. From the urinary system: infrequently - hematuria; very rarely - glomerulonephritis, an increase in the concentration of creatine in the blood. Others: often - bleeding from the puncture site of the vessels; very rarely - fever.

Application during pregnancy and lactation

There have been no adequate and strictly controlled clinical studies of the safety of the use of clopidogrel during pregnancy. Application is possible only in cases of extreme necessity. It is not known whether clopidogrel is excreted in human breast milk. If necessary, use during lactation should decide on the termination of breastfeeding. In experimental studies on animals, when using clopidogrel at doses of 300-500 mg / kg / day, no teratogenic effects and negative effects on fertility and fetal development were revealed. It has been established that clopidogrel and its metabolites are excreted in breast milk.

Application for violations of liver function

Clopidogrel is used with caution in patients with severely impaired liver function, in which hemorrhagic diathesis may occur.

special instructions

Clopidogrel is used with caution with an increased risk of bleeding due to trauma, surgery, and hemostatic disorders. For planned surgical interventions (if antiplatelet action is undesirable), clopidogrel should be canceled 7 days before surgery. Clopidogrel is used with caution in patients with severely impaired liver function, in which hemorrhagic diathesis may occur. When symptoms of excessive bleeding appear (bleeding of the gums, menorrhagia, hematuria), a study of the hemostatic system is shown (bleeding time, platelet count, tests of platelet functional activity). Regular monitoring of laboratory parameters of the functional activity of the liver is recommended. Use with caution simultaneously with warfarin, heparin, NSAIDs,long-term - with acetylsalicylic acid, because the safety of such an application has not yet been definitively established. In experimental studies, no carcinogenic and genotoxic effects were found. Influence on the ability to drive vehicles and use mechanisms The effect of clopidogrel on the ability to drive vehicles and use mechanisms has not been established.

Drug interactions

With simultaneous use with NSAIDs (including naproxen), the risk of gastrointestinal bleeding increases. With simultaneous use with acetylsalicylic acid, an increase in the antiplatelet effect is possible. Since clopidogrel can inhibit the activity of the isoenzyme CYP2C9, with simultaneous use with drugs metabolized with the participation of this isoenzyme (including phenytoin, tolbutamine), an increase in their plasma concentrations cannot be ruled out.