Description
Latin name
Koplavics
Release form
Tablets.
Packing
28 pcs
Indications
Prevention of atherothrombotic complications (in combination with acetylsalicylic acid) in patients with acute coronary syndrome:
without ST segment elevation (unstable angina pectoris or myocardial infarction without Q wave), including patients who underwent coronary artery surgery 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).
Special instructions
Due to the risk of bleeding and undesirable hematologic effects (see ² ÑSide effects ² Ñ) in the event of clinical symptoms that are suspected of causing bleeding during treatment, an urgent clinical blood test should be performed to determine APTT (activated partial thromboplastin time), platelet count, platelet functional activity indicators and conduct other necessary studies.
Due to the presence of two antiplatelet substances in the composition of Koplavix ®, it should be used with caution in patients at increased risk of bleeding due to injuries, surgical interventions or other pathological conditions, as well as in patients receiving non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin, IIb / Sha glycoprotein inhibitors and thrombolytic agents. It is necessary to carefully monitor patients to exclude signs of bleeding, including hidden, especially during the first weeks of treatment and / or after invasive cardiological procedures / surgical intervention. The combined use of clopidogrel with warfarin can increase the intensity of bleeding (see ² ÑInteraction with other drugs ² Ñ), therefore, with the exception of special rare clinical situations (such as the presence of a floating thrombus in the left ventricle, stenting in patients with atrial fibrillation or other indications for indirect anticoagulants) combined use of Coplavix and warfaria is not recommended.
If a patient has a planned operation, and there is no need for an antithrombotic effect, then 7 days before surgery, Coplavix ® should be canceled. Coplavix ® increases bleeding time and should be used with caution in patients with lesions predisposing to the development of bleeding (especially from the gastrointestinal tract and intraocular hemorrhage).
Very rarely, after the use of clopidogrel (sometimes even briefly), there have been cases of thrombocytopenic thrombohemolytic purpura (TGP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired renal function and fever. TTP is a potentially life-threatening condition that requires immediate treatment, including plasmapheresis. It has been clearly shown that in patients with recent transient ischemic brain attack or stroke who are at increased risk of recurring ischemia, a combination of acetylsalicylic acid and clopidogrel increases the chance of major bleeding. Therefore, when using the drug Koplaviks ® in such patients in all cases, including those when the beneficial effect of the combination has been proven, caution should be exercised.
There may be a relationship between acetylsalicylic acid and the occurrence of life-threatening Reye syndrome in children with prodromal infection.
Coplavix ® should be used with caution in patients with a history of peptic ulcers or gastrointestinal bleeding, or in patients with even minor symptoms of the upper gastrointestinal tract, which may be manifestations of stomach ulcers that can lead to gastric bleeding.
During treatment with Coplavix ®, symptoms from the upper gastrointestinal tract may occur at any time, such as gastralgia, heartburn, nausea, vomiting, and gastrointestinal bleeding. Despite the fact that during treatment with Coplavix ®, minor side effects from the gastrointestinal tract, such as dyspeptic disorders, are common, the attending physician should always exclude ulceration of the gastrointestinal mucosa and bleeding in these cases, even in the absence of a history of pathology from the gastrointestinal tract.
Patients should be informed of symptoms of adverse reactions from the gastrointestinal tract. Patients should also be warned that when taking Coplavix ® to stop the bleeding, they may need more time than usual, and that if they have any unusual (by localization or duration) bleeding, they should inform their doctor .
Before any upcoming surgery and before taking any new medication, patients should inform the doctor (including the dentist) about treatment with Coplavix ®. In patients with reduced metabolic function of the isofsprism of CYP2C19, when using clopidogrel in recommended doses, less active metabolite of clopidogrel is formed, its effect on platelet function decreases. Therefore, patients with acute coronary syndrome or undergoing percutaneous coronary intervention and taking clopidogrel may have a higher frequency of cardiovascular events than patients with normal function of the CYP2C19 isoenzyme.
This drug should not be taken by patients with rare hereditary disorders of galactose tolerance, with a lactase deficiency or with glucose-galactose malabsorption syndrome (see. “Composition”).
Impact on the ability to drive vehicles and engage in other potentially dangerous activities, requiring increased concentration of attention and speed of psychomotor reactions
Usually Koplaviks ® does not significantly affect the ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. However, if a patient experiences adverse side reactions from the nervous system and psyche (see the ² ÑSide Effects ² Ñ section), it is possible to decrease the concentration of attention and the speed of psychomotor reactions, which may interfere with such activities. In such cases, the question of the possibility of engaging in potentially hazardous activities should be decided by the attending physician.
Composition
Active ingredient: 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 silicon dioxide – 0.631 corn starch -11.111 mg.
Dosage and administration of
Adults and the elderly
Plavix ® should be taken orally, regardless of food intake. 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 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 dose of acetylsalicylic acid recommended 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.
Regarding the maintenance dose of clopidogrel, 75 mg, then for its administration, Plavike ® 75 mg tablets are produced.
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 the combination of clopidogrel + acetylsalicylic acid, the risk of major, minor and other bleeding was significantly higher: non-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 against 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: simultaneous administration with clopidogrel can increase the intensity of bleeding, so the use of this combination is not recommended. Glycoprotein IIb / IIIa Blockers: the administration of IIb / IIIa glycoprotein blockers together with clopidogrel requires caution in patients with an increased risk of bleeding (with injuries and surgical interventions or other pathological conditions). Acetylsalicylic acid: acetylsalicylic acid does not change the effect of clopidogrel, which inhibits ADP inducible inducible inducible , but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. Nevertheless, simultaneous administration of acetylsalicylic acid with clopidogrel 500 mg 2 times a day for 1 day did not cause a significant increase in bleeding time caused by clopidogrel. Between clopidogrel and acetylsalicylic acid, a pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Therefore, with their simultaneous use, caution should be exercised, although in clinical studies, patients received combination therapy with clopidogrel and acetylsalicylic acid for up to one year. Heparin: according to a clinical trial conducted with healthy individuals, when taking clopidogrel, there was no need to change the dose of heparin and its anticoagulant effect did not change. The simultaneous use of heparin did not change the antiplatelet effect of clopidogrel. Between clopidogrel and heparin, a pharmacodynamic interaction is possible, which can increase the risk of bleeding, so the simultaneous use of these drugs requires caution. Thrombolytics: the safety of co-administration of clopidogrel, fibrin-specific or fibrin-specific thrombolytic drugs and heparin was studied in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that 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 healthy volunteers, the combined use of clopidogrel and naproxen increased latent blood loss through the gastrointestinal tract. However, due to the lack of studies on the interaction of clopidogrel with other NSAIDs, it is currently not known whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel with other NSAIDs. Therefore, the appointment of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be carried out with caution .. Another combination therapy Since clopidogrel is metabolized before its active metabolite is formed in part by the isoenzyme CYP2C19, the use of drugs that inhibit this system can lead to a decrease in the concentration of the active metabolite of clopidogrel. The clinical significance of this interaction has not been established. The simultaneous use of strong or moderate CYP2C19 inhibitors (such as omeprazole) with clopidogrel should be avoided. If proton pump inhibitors should be taken concurrently with clopidogrel, a proton pump inhibitor with the lowest CYP2C19 isoenzyme inhibition activity, such as pantoprazole, should be used. overdose Symptoms of Clopidogrel overdose can lead to an increase in bleeding time, with subsequent bleeding complications. Treatment When bleeding occurs, appropriate treatment is required. Clopidogrel antidote has not been established. If rapid recovery of prolonged bleeding time is required, platelet transfusion is recommended. Storage conditions Do not store above 30 ° C. Shelf life 3 years. Active ingredient acetylsalicylic acid, Clopidogrel Terms and conditions prescription Dosage form tablets Prescribing Prescribing Adults as prescribed by a doctor Sanofi-Aventis, France
