Description of the active substance:
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
Inhibitor of platelet aggregation. Selectively inhibits the binding of adenosine diphosphate (ADP) to platelet receptors and activation of the GPIIb / IIIa complex, thereby inhibiting platelet aggregation. It also inhibits platelet aggregation caused by other agonists by blocking the increase in platelet activity released by ADP. Does not affect the activity of PDE.
Clopidogrel irreversibly changes ADP receptors on platelets, so platelets remain non-functional throughout life, and normal function recovery occurs as they update (approximately 7 days later).
PHARMACOKINETICS
After ingestion at a dose of 75 mg, clopidogrel is rapidly absorbed from the digestive tract. However, the concentration in the blood plasma increases slightly and after 2 hours after taking does not reach the level that can be determined (0.025 Ојg / l).
Intensively metabolized in the liver. The main metabolite is an inactive derivative of carboxylic acid and constitutes about 85% of the starting material circulating in the plasma. C max of this metabolite in the blood plasma after repeated use 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 dependence 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 bond remains unsaturated in vitro over a wide range of concentrations.
After ingestion of 14 C-labeled clopidogrel, about 50% of the dose taken is excreted in the urine and approximately 46% with feces for 120 hours. The T 1/2 of themain metabolite is 8 hours.
Compared to healthy young volunteers, the plasma metabolism of the main metabolite is significantly higher in elderly patients (aged 75 years and older), with no changes in platelet aggregation and bleeding time.
In severe kidney disease (KK 5-15 ml / min), the concentration of the main metabolite in the blood plasma is lower than in cases of kidney disease of moderate severity (KK 30-60 ml / min) and in healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation decreased compared to that in healthy volunteers, bleeding time increased to the same extent as in healthy volunteers.
INDICATIONS
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 elevation of the ST segment with the possibility of carrying out thrombolytic therapy; without ST segment elevation (unstable angina, myocardial infarction without Q-wave), incl. in patients undergoing stenting.
Prophylaxis of thrombotic and thromboembolic complications, including stroke, with atrial fibrillation (atrial fibrillation) with at least one risk factor for vascular complications, the inability to take indirect anticoagulants and the low risk of bleeding (in combination with acetylsalicylic acid).
DOSING MODE
Take 1 time / day.
The initial and maintenance dose is 75 mg / day. The loading dose is 300 mg / day.
The scheme of application depends on the indications and the clinical situation.
SIDE EFFECT
From the coagulation system of the blood: often - bleeding; infrequently, an increase in bleeding time.
From the digestive system: very often - gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia; infrequently - ulcers of the stomach and duodenum, vomiting, nausea, constipation, bloating; rarely - retroperitoneal hemorrhage; very rarely - gastrointestinal bleeding and retroperitoneal hemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative colitis or lymphocytic colitis), stomatitis, acute liver failure, hepatitis, abnormal liver function.
From the hemopoietic 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 cases of fatal cases have been reported), headache, paresthesia, dizziness; very rarely - violations of taste perception, hallucinations, confusion.
From the sense organs: infrequently - eye hemorrhages (conjunctival, in the tissue and retina of the eye); rarely - vertigo.
From the cardiovascular system: very rarely - vasculitis, lowering blood pressure.
From the respiratory system: often - nosebleeds; very rarely - bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonia.
From the side of the immune system: very rarely - serum sickness, anaphylactoid reactions.
From the skin and subcutaneous tissues: often - subcutaneous bruising; infrequently - a rash, itching, purpura (subcutaneous hemorrhage); very rarely - bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) angioedema, erythematous rash, urticaria, eczema, flat lichen.
From the musculoskeletal system: very rarely - hemorrhages in the 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.
Other: often - bleeding from the point of vascular puncture; very rarely - a fever.
CONTRAINDICATIONS
Acute bleeding (including peptic ulcer or intracranial hemorrhage), severe hepatic insufficiency, pregnancy, lactation (breastfeeding), children and adolescents under 18, hypersensitivity to clopidogrel.
PREGNANCY AND LACTATION
Adequate and strictly controlled clinical studies of the safety of clopidogrel during pregnancy have not been conducted. Application is possible only in cases of extreme necessity.
It is not known whether clopidogrel is excreted in human milk. If it is necessary to use during the lactation period, the question of stopping breastfeeding should be solved.
In experimental animal studies using clopidogrel at doses of 300-500 mg / kg / day, there was no teratogenic effect and a negative effect on fertility and fetal development. It has been established that clopidogrel and its metabolites are excreted in breast milk.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution apply clopidogrel in patients with severe violations of the liver, in which there may be a hemorrhagic diathesis.
SPECIAL INSTRUCTIONS
With care apply clopidogrel with an increased risk of bleeding due to trauma, surgical interventions, violations of the hemostasis system. When planned surgical interventions (if antiaggregant effect is undesirable) clopidogrel should be canceled 7 days before surgery.
With caution apply clopidogrel in patients with severe violations of the liver, in which there may be a hemorrhagic diathesis.
When symptoms of excessive bleeding occur (bleeding gums, menorrhagia, hematuria), a study of the hemostatic system (bleeding time, platelet count, and platelet function tests) is shown. It is recommended that the laboratory indicators of the functional activity of the liver be checked regularly.
With caution apply simultaneously with warfarin, heparin, NSAIDs, long-term with acetylsalicylic acid, tk. At present, the security of such an application has not been finally established.
In experimental studies, there was no evidence of carcinogenic and genotoxic effects.
Impact on the ability to drive vehicles and manage mechanisms
The influence of clopidogrel on the ability to drive vehicles and control mechanisms has not been established.
DRUG INTERACTION
When used simultaneously with NSAIDs (including naproxen), the risk of gastrointestinal bleeding increases.
When used simultaneously with acetylsalicylic acid, antiplatelet effect may be increased.
Since clopidogrel can inhibit the activity of the isoenzyme CYP2C9, while simultaneous use with drugs metabolized with the participation of this isoenzyme (including with phenytoin, tolbutamine), it is impossible to exclude an increase in their concentrations in the blood plasma.
