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Acetylsalicylic acid, Clopidogrel

Dr. Reddy`s
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Clopidogrel is a prodrug, one of the active metabolites of which is an inhibitor of platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to the P2Y12 platelet receptor and subsequent ADP-mediated activation of the GPIIb / IIIa complex, leading to suppression of platelet aggregation. Due to irreversible binding, platelets remain immune to ADP stimulation for the rest of their life (approximately 7-10 days), and the restoration of normal platelet function occurs at a rate corresponding to the rate of platelet renewal. Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the increased platelet activation by released ADP. Since the formation of an active metabolite occurs with the help of isoenzymes of the P450 system, some of which may differ in polymorphism or may be inhibited by other drugs, not all patients may have adequate inhibition of platelet aggregation. With a daily intake of clopidogrel at a dose of 75 mg, from the very first day of administration, there is a significant suppression of ADP-induced platelet aggregation, which gradually increases over 3-7 days and then reaches a constant level (upon reaching an equilibrium state). In an equilibrium state, platelet aggregation is suppressed by an average of 40-60%. After discontinuing clopidogrel, platelet aggregation and bleeding time gradually return to baseline, on average, within 5 days ... Clopidogrel is able to prevent the development of atherothrombosis in any localization of atherosclerotic vascular lesions, in particular, with lesions of the cerebral, coronary or peripheral arteries. The ACTIVE-A clinical trial showed that in patients with atrial fibrillation who had at least one risk factor for vascular complications, but were unable to take indirect anticoagulants, clopidogrel in combination with acetylsalicylic acid (compared with taking only acetylsalicylic acid) reduced the incidence of combined stroke, myocardial infarction, systemic thromboembolism outside the central nervous system (CNS), or vascular death, largely by reducing the risk of stroke. The effectiveness of taking clopidogrel in combination with acetylsalicylic acid was detected early and lasted up to 5 years. The decrease in the risk of major vascular complications in the group of patients taking clopidogrel in combination with acetylsalicylic acid was mainly due to a greater decrease in the incidence of strokes. The risk of developing a stroke of any severity when taking clopidogrel in combination with acetylsalicylic acid decreased, and there was also a tendency to a decrease in the incidence of myocardial infarction in the group treated with clopidogrel in combination with acetylsalicylic acid, but there were no differences in the incidence of non-CNS thromboembolism or vascular death. In addition, taking clopidogrel in combination with acetylsalicylic acid reduced the total number of days of hospitalization for cardiovascular reasons.

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Acetylsalicylic acid, Clopidogrel
The frequency of adverse reactions that were observed during the above clinical studies is presented in accordance with the WHO classification: very often (≥ 10%); often (≥ 1% and <10%); infrequently (≥ 0.1% and <1%); rarely (≥ 0.01% and <0.1%); very rare (<0.01%); frequency is unknown - it is not possible to determine the frequency of occurrence of side effects from the available data. Nervous system disorders Uncommon: headache, dizziness, paresthesia. Rarely: vertigo. Gastrointestinal disorders Often: dyspepsia, abdominal pain, diarrhea. Uncommon: nausea, gastritis, bloating, constipation, vomiting, stomach ulcer, duodenal ulcer. Skin and subcutaneous tissue disorders Uncommon: rash, itching. Blood and lymphatic system disorders Uncommon: an increase in bleeding time, a decrease in the number of platelets in the peripheral blood; leukopenia, a decrease in the number of neutrophils in the peripheral blood, eosinophilia. Post-marketing experience with the drug Blood and lymphatic system disorders The frequency is unknown: cases of serious bleeding, mainly subcutaneous, musculoskeletal, ocular hemorrhages (conjunctival, into the tissues and retina of the eye), bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage), nosebleeds, hematuria and bleeding from postoperative wounds and cases of bleeding with lethal outcome (especially intracranial hemorrhage, gastrointestinal bleeding and retroperitoneal hemorrhage), agranulocytosis, granulocytopenia, aplastic anemia / pancytopenia, thrombotic thrombocytopenic purpura (TTP), acquired hemophilia A. Heart disorders Frequency unknown: Kounis syndrome (vasospastic allergic angina / allergic myocardial infarction) due to a hypersensitivity reaction to clopidogrel. Immune system disorders Frequency unknown: anaphylactoid reactions, serum sickness; cross-allergic and hematological reactions with other thienopyridines (such as ticlopidine, prasugrel) [see. section "Special instructions"]. Mental disorders Frequency unknown: confusion, hallucinations. Nervous system disorders Frequency unknown: disturbances in taste. Vascular disorders Frequency not known: vasculitis, decreased blood pressure. Liver and biliary tract disorders Frequency unknown: hepatitis (non-infectious), acute liver failure. Skin and subcutaneous tissue disorders Frequency unknown: macular-papular erythematous or exfoliative rash, urticaria, pruritus, angioedema, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), acute generalized eczematous pustulosis, drug-induced hypersensitivity syndrome, and drug-induced hypersensitivity syndrome (DRESS syndrome), eczema, lichen planus. Musculoskeletal and connective tissue disorders Frequency unknown: arthralgia (joint pain), arthritis, myalgia. Kidney and urinary tract disorders Frequency not known: glomerulonephritis. Genital and breast disorders Frequency unknown: gynecomastia. General disorders and disorders at the injection site Frequency not known: fever. Laboratory and instrumental data The frequency is unknown: deviation from the norm of laboratory parameters of the functional state of the liver, an increase in the concentration of creatinine in the blood.
  • Brand name: Plagryl
  • Active ingredient: Acetylsalicylic acid, Clopidogrel
  • Manufacturer: Dr. Reddy`s
  • Country of Origin: India

Studies and clinical trials of Acetylsalicylic acid, Clopidogrel (Click to expand)

  1. Predictors and time trends in clopidogrel and proton pump inhibitor coprescription with low-dose acetylsalicylic acid
  2. Review of an article: Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. Jill J.F. Belch, MD, FRCP, John Dormandy, MD, FRCS, and the CASPAR Writing Committee, Dundee and London, United Kingdom (J Vasc Surg 2010;52:825-33)
  3. Dual low response to acetylsalicylic acid and clopidogrel is associated with myonecrosis and stent thrombosis after coronary stent implantation
  4. Regarding “Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial”
  5. Superior efficacy of clopidogrel plus acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in healthy volunteers
  6. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
  7. Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment
  9. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial
  10. The impact of CYP3A5*1/*3, PIA1/A2 and T744C polymorphisms on clopidogrel and acetylsalicylic acid response variability in Mexican population
  11. Bilateral Hemothorax Secondary to Combined Antiplatelet Therapy With Clopidogrel and Acetylsalicylic Acid
  12. Effects of rivaroxaban, acetylsalicylic acid and clopidogrel as monotherapy and in combination in a porcine model of stent thrombosis
  13. Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo
  14. Low prevalence of clopidogrel and acetylsalicylic acid resistance in patients with acute myocardial infarction and pantoprazole treatment in everyday practice
  15. The Pharmacokinetics and Safety of a Fixed-Dose Combination of Acetylsalicylic Acid and Clopidogrel Compared With the Concurrent Administration of Acetylsalicylic Acid and Clopidogrel in Healthy Subjects: A Randomized, Open-Label, 2-Sequence, 2-Period, Single-Dose Crossover Study
  16. Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor
  17. Pharmacoeconomic Evaluation Acceptability of Clopidogrel Versus Acetylsalicylic Acid in Patients with Cardiovascular Disease for Stroke Prevention in Ukraine
  18. We-P11:236 Acetylsalicylic acid and clopidogrel resistance: Possible role of risk factors, medication and hemorheological variables
  19. W1004 Time Trends in the Prescription of Low-Dose Acetylsalicylic Acid, Clopidogrel and Proton Pump Inhibitors in UK Primary Care
  21. Uneventful Removal of an Epidural Catheter Guided by Impedance Aggregometry in a Patient With Recent Coronary Stenting and Treated With Clopidogrel and Acetylsalicylic Acid
  22. Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

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