Description
Latin name
Koplavics
Release form
Tablets.
Packing
100 pcs.
indications Prevention of atherothrombotic complications (in combination with acetylsalicylic acid) in patients with acute coronas molecular syndrome: without lifting segment ST (unstable angina or myocardial infarction without tooth Q), including patients who who underwent stenting with percutaneous coronary intervention
with ST segment elevation (acute myocardial infarction)
Contraindications
Hypersensitivity to clopidogrel or any of the excipients of the drug.
Severe liver failure.
Acute bleeding, such as peptic ulcer bleeding or intracranial hemorrhage.
Rare hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.
Pregnancy and lactation.
Children under 18 years of age (safety and efficacy not established).
Use during pregnancy and lactation
Contraindicated.
Composition
1 tablet contains clopidogrel hydrosulfate in form II – 97.875 mg (in terms of clopidogrel 75 mg), acetylsalicylic acid – 100 mg.
Excipients: mannitol 68.925 mg, macrogol-6000 34,000 mg, microcrystalline cellulose -144.764 mg, low-substituted hyprolose – 19.567 mg, hydrogenated castor oil – 3.300 mg, stearic acid – 1.161 mg, colloidal silica – 0.631 -11.111 mg.
Dosage and administration
Adults and the elderly: Coplavix should be taken orally, regardless of the meal. This tablet containing 300 mg of clopidogrel is intended for use as a loading dose in patients with acute coronary syndrome.
Acute coronary syndrome without ST segment elevation (unstable angina, myocardial infarction without Q wave)
Clopidogrel treatment should be started with a single loading dose of 300 mg and then continued with a dose of 75 mg once a day (in combination with acetylsalicylic acid in doses of 75-325 mg per day). Since the use of higher doses of acetylsalicylic acid is associated with an increased risk of bleeding, the recommended dose of acetylsalicylic acid for this indication should not exceed 100 mg. The maximum beneficial effect is observed by the third month of treatment. The course of treatment is up to 1 year.
Acute coronary syndrome with ST-segment elevation (acute myocardial infarction with ST-segment elevation)
Clopidogrel is prescribed once at a dose of 75 mg once a day with the initial single dose of a loading dose of 300 mg in combination with acetylsalicylic acid and thrombolytics (or without thrombolytics). Combination therapy is started as soon as possible after the onset of symptoms and continues for at least four weeks. In patients older than 75 years of age, treatment with clopidogrel should begin without taking its loading dose.
As for the maintenance dose of clopidogrel, which is 75 mg, Plavike 75 mg tablets are made to take it.
Patients with a genetically decreased function of the CYP2CJ9 isoenzyme
The status of a weak CYP2C19 metabolizer is associated with a decrease in the antiplatelet effect of clopidogrel. The regimen for the use of high doses (600 mg is the loading dose, then 150 mg once a day daily) in weak metabolizers increases the antiplatelet effect of clopidogrel. However, the optimal dosage regimen for patients with reduced metabolism using the CYP2C19 isoenzyme in clinical trials on clinical outcomes has not yet been established.
Side effects of
Bleeding
In the CARPIE
clinical trial, the total frequency of all bleeding in patients who received either clopidogrel or acetylsalicylic acid was 9.3%. The frequency of severe bleeding with clopidogrel was 1.4%, and with acetisalicylic acid -1.6%.
In patients receiving clopidogrel and in patients receiving acetylsalicylic acid, gastrointestinal bleeding occurred in 2.0% and 2.7% of cases, respectively, and hospitalization was required in 0.7% and 1.1% of cases.
The frequency of other bleeding was higher in patients receiving clopidogrel than in patients receiving acetylsalicylic acid (7.3% versus 6.5%, respectively). However, the frequency of heavy bleeding in both groups was the same (0.6% versus 0.4%). Most often, purpura / bruising and nosebleeds were observed in both groups. Less common were hematomas, hematuria and eye hemorrhages (mainly conjunctival).
The incidence of intracranial hemorrhage was 0.4% in patients receiving clopidogrel, and 0.5% in patients receiving acetylsalicylic acid.
In the CURE
clinical trial, the use of a combination of clopidogrel with acetylsalicylic acid compared to a combination of placebo with acetylsalicylic acid did not lead to a statistically significant increase in the frequency of life-threatening bleeding (2.2% and 1.8%, respectively) and fatal bleeding ( 0.2% and 0.2%, respectively). However, when using a combination of clopidogrel + acetylsalicylic acid, the risk of major, minor and other bleeding was significantly higher: life-threatening major bleeding, mainly gastrointestinal and at the puncture site (1.6%, clopidogrel + acetylsalicylic acid versus 1.0 % – placebo + acetylsalicylic acid) and minor bleeding (5.1% – clopidogrel + acetylsalicylic acid versus 2.4% – placebo + acetylsalicylic acid). The incidence of intracranial hemorrhage in both groups was 0.1%.
The frequency of major bleeding when using the combination of clopidogrel + acetylsalicylic acid depended on the dose of the latter (200 mg – 4.9%), as well as their frequency when using one acetylsalicylic acid (200 mg – 4.0%).
During the study, the risk of bleeding (life-threatening, large, small, etc.) decreased both when taking a combination of clopidogrel and acetylsalicylic acid, and when taking only one acetylsalicylic acid, accounting for 9.6% (599/6259) n 6, respectively , 6% (413/6303) (0-1 month of treatment), 4.5% (276/6123) and 2.3% (144/6168) (1-3 month of treatment), 3.8% (228 / 6037) and 1.6% (99/6048) (3-6 months of treatment), 3.2% (162/5005) n 1.5% (74/4972) (6-9 months of treatment), 1.9 % (73/3841) n 1.0% (40/3844) (9-12 months of treatment).
In patients who stopped taking the drug more than 5 days before coronary artery bypass grafting, there was no increased incidence of major bleeding within 7 days after this intervention (4.4% with clopidogrel + acetylsalicylic acid versus 5.3% with one acetylsalicylic acid). In patients who remained on antiplatelet therapy for the last five days before coronary artery bypass grafting, the frequency of these events after the intervention was 9.6% (clopidogrel + acetylsalicylic acid) and 6.3% (one acetylsalicylic acid).
In the CLARITY
clinical trial, a general increase in bleeding rate was observed in the clopidogrel + acetylsalicylic acid group (17.4%) compared with the placebo + acetylsalicylic acid group (12.9%). The frequency of major bleeding was similar in both groups (1.3% and 1.1% in the clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic acid groups, respectively) and practically did not depend on the initial characteristics of patients and the type of fibrinolytic or heparin therapy. The frequency of lethal bleeding (0.8% and 0.6% in the clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic acid groups, respectively) and intracranial hemorrhages (0.5% and 0.7% in the clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic groups acid, respectively) was low and did not significantly differ in both treatment groups.
In the COMMIT clinical trial
, the overall incidence of non-cerebral major bleeding or cerebral hemorrhage was low and did not significantly differ in both groups (0.6% and 0, 5% in the clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic acid groups, respectively). Hematologic disorders
In a clinical trial of CAPPRIE
Severe neutropenia (Frequency of severe thrombocytopenia ( In clinical trials of CURE and CLARITY
, the number of patients with thrombocytopenia or neutropenia was the same in both groups.
Other clinically significant side effects that were observed. CAPIE, CURE, CLARITY and COMMIT trials with a frequency of> 0.1%, as well as all serious side effects, are presented below according to the WHO classification of side effects. traveling: frequent (> 1/100, 1/1000, 1/10000, Disorders of the central and peripheral nervous system: Infrequently: headache, dizziness and paresthesia. Rarely: vertigo.
Disorders of the gastrointestinal tract: Often: diarrhea, abdominal pain, dyspepsia. Uncommon: nausea, gastritis, flatulence, constipation, vomiting, stomach ulcer and duodenal ulcer.
Hemostatic disorders: Infrequently: prolonged bleeding time.
Blood disorders: Infrequently: thrombocytopenia, leukopenia, neutropenia and eosinophilia.
Disorders of the skin and subcutaneous tissue: Infrequently: rash and itching.
Adverse effects observed in the post-marketing period of clopidogrel use in monotherapy and in combination with acetylsalicylic acid: Bleeding: The most frequent reports of adverse effects were reports of bleeding that were most often observed in the first month of treatment. Several cases of fatal bleeding have been reported, mainly intracranial, gastrointestinal and retroperitoneal. There are reports of severe cases of hemorrhage in the skin tissue (purpura), hemorrhages in the joints and muscles (hemarthrosis, hematoma), eye hemorrhages (conjunctival, in the tissue and retina), nosebleeds, and bleeding from the respiratory system (hemoptysis, pulmonary hemorrhage), hematuria and bleeding from an operating wound. In patients taking clopidogrel simultaneously with acetylsalicylic acid or simultaneously with acetylsalicylic acid and heparin, cases of severe bleeding were noted (see Interaction with other drugs and Special instructions ).
Other side effects: In addition to the side effects identified in the clinical trials listed above, according to the results of spontaneous reports, the side effects presented below were recorded, divided into groups according to the classification of adverse side reactions in accordance with the damage to organs and organ systems presented in the medical dictionary for regulatory activities of MedDRA). The frequency of all spontaneous reports of side effects observed with clopidogrel was very low (they are classified as very rare Blood disorders: – Anemia (due to clopidogrel or acetylsalicylic acid).
– Thrombocytopenic thrombohemolytic purpura (1: 200000) severe thrombocytopenia (platelet count <30x109 / l), agranulocytosis, granulocytopenia, aplastic anemia (pancytopenia) (due to clopidogrel). Immune system disorders: – Angioneurotic edema, urticaria, anaphylactoid reactions, serum sickness (due to clopidogrel), anaphylactic shock, aggravation of food allergy symptoms, (caused by acetylsalicylic acid). Mental disorders: – Confusion, hallucinations (due to clopdogrel). Violations of the nervous system: – Changes in taste (due to clopidogrel). Hearing disorders and labyrinth disorders: – Tinnitus, hearing loss (due to acetylsalicylic acid and usually occurring in case of overdose). Violations of the vascular system: – Vasculitis, decreased blood pressure (due to clopidogrel). Respiratory disorders: – Bronchospasm (due to clopidogrel or acetylsalicylic acid), interstitial pneumonitis (due to clopidogrel). Disorders of the gastrointestinal tract: – Pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis (due to clopidogrel). – An ulcer or ulcerative perforation of the stomach or duodenum, symptoms of damage to the upper gastrointestinal tract (GIT), such as gastralgia (due to acetylsalicylic acid). Disorders from the hepatobiliary system: – Acute liver failure, hepatitis (due to clopidogrel). Disorders of the skin and subcutaneous tissues – maculopapular or erythematous rash, itching, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), eczema and lichen planus (due to clopidogrel). Disorders from the musculoskeletal system: – Arthralgia, arthritis, myalgia (due to clopidogrel). Disorders of the kidneys and urinary tract: – Glomerulopathy (due to clopidogrel), acute renal failure (especially in patients with already existing renal failure, heart failure, nephritic syndrome or with the simultaneous use of diuretics) (caused by acetylsalicylic acid). Metabolic disorders: – Hypoglycemia, gout (due to acetylsalicylic acid). Common disorders: – Fever (due to clopidogrel). Changes in laboratory parameters: – Abnormal biochemical parameters of the functional state of the liver, an increase in the concentration of creatinine in the blood (due to clopidogrel). Drug Interaction Warfarin: Co-administration with clopidogrel may increase bleeding rates, so this combination is not recommended. Glycoprotein IIb / IIIa Blockers: The administration of glycoprotein IIb / IIIa blockers with clopidogrel requires caution in patients who are at increased risk of bleeding (trauma and surgery or other pathological conditions) (see Special instructions). Acetylsalicylic acid: acetylsalicylic acid does not alter the effect of clopidogrel inhibiting ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced aggregation. However, concurrent with clopidogrel receiving acetylsalicylic acid at 500 mg 2 times a day for 1 day did not cause a significant increase in bleeding time caused by clopidogrel intake. A pharmacodynamic interaction is possible between clopidogrel and acetylsalicylic acid, which increases the risk of bleeding. Therefore, caution should be exercised when administered concurrently, although in clinical trials patients received combination therapy with clopidogrel and acetylsalicylic acid for up to one year. Heparin : According to a clinical trial conducted with the participation of healthy individuals, clopidogrel was not required to change the dose of heparin and did not change its anticoagulant effect. Co-administration of heparin did not alter the antiaggregant effect of clopidogrel. A pharmacodynamic interaction is possible between clopidogrel and heparin, which may increase the risk of bleeding, so the concomitant use of these drugs requires caution. Thrombolytics: the safety of co-administration of clopidogrel, fibrin-specific or fibrin-specific thrombolytic drugs and heparin has been studied in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that of which was observed in the case of the combined use of thrombolytic agents and heparin with acetylsalicylic acid. Nonsteroidal anti-inflammatory drugs (NSAIDs): In a clinical study conducted with the participation of healthy volunteers, the combined use of clopidogrel and naproxen increased the hidden blood loss through the gastrointestinal tract. However, due to the lack of studies on the interaction of clopidogrel with other NSAIDs, it is currently unknown whether there is an increased risk of gastrointestinal bleeding when receiving clopidogrel with other NSAIDs. Therefore, the use of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be performed with caution. Another combination therapy Since clopidogrel is metabolized to its active metabolite in part by the CYP2C19 isoenzyme, the use of drugs inhibiting this system may lead to a decrease in the concentration of the active metabolite of clopidogrel. The clinical significance of this interaction has not been established. Co-administration of clopidogrel with strong or moderate CYP2C19 inhibitors (eg, omeprazole) should be avoided. If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the lowest CYP2C19 isoenzyme inhibition activity such as pantoprazole should be used. overdose No data is available on an overdose of Coplavix ®. Symptoms and treatment of clopidogrel overdose Clopidogrel overdose can lead to an increase in bleeding time with subsequent bleeding complications. If bleeding occurs, appropriate treatment is required. Clopidogrel antidote has not been established. If rapid correction of prolonged bleeding time is required, platelet transfusion is recommended. Symptoms and treatment of acetylsalicylic acid overdose Moderate degree of overdose: tinnitus, hearing loss, headaches, vertigo. Severe overdose: fever, hyperventilation, ketosis, respiratory alkalosis, metabolic acidosis, coma, cardiovascular failure (collapse), respiratory failure, severe hypoglycemia. In the case of a severe overdose of acetylsalicylic acid, the following measures should be taken: control of acid-base balance, intravenous administration of sodium bicarbonate (for the purpose of forced alkalization of urine to accelerate salicylate removal), hemodialysis may be used if necessary. Storage conditions Store at a temperature not exceeding 30 ° C. The Expiration of is 3 years. Deystvuyuschee substances Atsetylsalytsylovaya acid , Clopidogrel Terms of delivery from pharmacies Prescription Dosage form Dosage form tablets Sanofi-Aventis, France
