Pharmacological properties
Pharmacodynamics. Clopidogrel selectively inhibits the binding of ADP to its receptors on the platelet surface, blocks platelet activation and, thus, inhibits their aggregation. It also inhibits platelet aggregation caused by other agonists. Inhibition of platelet aggregation is observed 2 hours after oral administration of a single dose of the drug. With repeated administration, the effect increases, and a stable state is achieved after 3-7 days of treatment (the average level of inhibition of aggregation is 40-60%). Platelet aggregation and bleeding time return to baseline levels on average 7 days after discontinuation of the drug, as platelets are renewed.
Pharmacokinetics. After oral administration, the drug is rapidly absorbed in the gastrointestinal tract. Its concentration in blood plasma is insignificant and is not determined 2 hours after administration (less than 0.025 μg/l). It is rapidly metabolized in the liver. Its main metabolite (85% of the compound circulating in plasma) is inactive. The active thiol metabolite binds rapidly and irreversibly to platelet receptors. It is not present in blood plasma. Clopidogrel and the main circulating metabolite bind reversibly to plasma proteins.
After oral administration, about 50% of the dose is excreted in the urine and 46% in the feces within 120 hours after administration. T ½ of the main metabolite is 8 hours.
The concentration of the main metabolite in the blood plasma in elderly patients (75 years and older) is significantly higher, however, higher plasma concentrations are not accompanied by changes in platelet aggregation and bleeding time.
Indication
Prevention of ischemic disorders (myocardial infarction, ischemic stroke, sudden coronary death, peripheral arterial thrombosis) in patients with atherosclerosis; prevention of repeated myocardial infarction and ischemic stroke.
Application
The drug is taken orally, 1 tablet (75 mg) once a day, regardless of meals.
Patients with acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without a pathological Q wave on the ECG) on the first day of treatment - 4 tablets (300 mg), on the following days - 1 tablet once a day, regardless of meals.
The duration of treatment is determined by the doctor depending on the clinical picture of the disease.
Contraindication
Hypersensitivity to the drug; severe liver disease; acute bleeding (intracranial hemorrhage) and diseases leading to their development (gastric and duodenal ulcer in the acute stage, nonspecific ulcerative colitis); age up to 18 years.
Side effects
From the blood system: leukopenia, decrease in the number of neutrophils and eosinophilic granulocytes, increase in bleeding time and decrease in the number of platelets. very rarely: thrombocytopenic thrombohemolytic purpura, severe thrombocytopenia, granulocytopenia, agranulocytosis, anemia and aplastic anemia / pancytopenia. bleeding of various localization. most cases of bleeding were noted during the 1st month of treatment.
From the gastrointestinal tract: abdominal pain, dyspepsia, diarrhea; rarely - constipation, exacerbation of gastric and duodenal ulcers.
From the musculoskeletal system: very rarely - arthralgia, arthritis.
From the urinary system: very rarely - glomerulonephritis, increased serum creatinine levels.
From the side of the central nervous system: headache, dizziness, paraesthesia. Very rarely - confusion, hallucinations, taste disturbance.
Allergic reactions: skin rashes, anaphylactoid reactions.
Others: very rarely - fever.
Special instructions
It is prescribed with caution to patients with an increased risk of bleeding due to trauma, surgical interventions, or impaired hemostasis. In case of planned surgical interventions (if antiplatelet effect is undesirable), the course of treatment with the drug should be stopped 7 days before the operation.
It is prescribed with caution to patients with severe liver dysfunction, in whom hemorrhagic diathesis may occur.
Dose adjustment is not required for elderly patients or those with renal insufficiency.
Patients should be warned that since stopping bleeding that occurs with the use of the drug takes longer, they should inform their doctor about any unusual bleeding. Patients should also inform their doctor about taking the drug if they are scheduled for surgery (surgery, dentistry, etc.) or if the doctor prescribes a new drug for the patient.
If symptoms of excessive bleeding appear (bleeding gums, menorrhagia, hematuria), a study of the hemostasis system (bleeding time, platelet count, platelet functional activity tests) is indicated.
Regular monitoring of laboratory parameters of liver function is recommended.
Use during pregnancy and breastfeeding. The use of the drug during pregnancy is contraindicated.
If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.
Children: The safety and effectiveness of the drug in individuals under the age of 18 have not been established.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The drug does not affect the ability to drive vehicles and does not reduce the reaction rate.
Clopidogrel increases the risk of gastrointestinal bleeding with the use of NSAIDs.
Concomitant use with warfarin is not recommended, as increased bleeding intensity may occur.
Concomitant use with acetylsalicylic acid or heparin does not affect the antiplatelet effect of the drug, however, the safety of long-term use of such combinations has not yet been established, therefore, the simultaneous use of these drugs requires caution.
Concomitant use with phenytoin and tolbutamide may increase their plasma levels. However, their concomitant use with clopidogrel is safe.
No clinically significant drug interactions with diuretics, β-adrenergic blockers, ACE inhibitors, calcium channel blockers, antacids, hypoglycemic, hypocholesterolemic and hormone replacement drugs, antiepileptic drugs, phenobarbital, cimetidine, digoxin and theophylline have been observed.
Overdose
Symptoms: possible prolongation of bleeding time.
Treatment. If rapid correction of the rheological properties of the blood is necessary, platelet mass is transfused.
Storage conditions
In a dry, dark place at a temperature not exceeding 25 °C.
