Coplavix pills 100mg+75mg, 28pcs

Composition

Active ingredient:

clopidogrel hydrosulfate in form II – 97.875 mg (based on clopidogrel 75 mg), acetylsalicylic acid-100 mg.

Auxiliary substances:  

mannitol 68,925 mg,

macrogol-6000 34,000 mg,

microcrystalline cellulose -144,764 mg

of hyprolose discosoma-Holy 19,567 mg,

castor oil hydrogenated – 3,300 mg,

stearic acid 1,161 mg,

silicon dioxide colloid -0,631 mg,

corn starch -11,111 mg.

Pharmacological action

of KOPLEWICZ is a prodrug, one of the metabolites of which is active and inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to the platelet P2Y12 receptor and subsequent ADP-mediated activation of the glycoprotein IIb/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 caused by agonists other than ADP is also inhibited by blocking enhanced platelet activation by released ADP. Since the formation of the active metabolite occurs with the help of isoenzymes of the P 450 system, some of which may differ in polymorphism or may be inhibited by other drugs, not all patients can adequately inhibit platelet aggregation (see “Pharmacokinetics, Pharmacogenetics”). When taking clopidogrel daily at a dose of 75 mg from the first day of use, there is a significant suppression of ADP-induced platelet aggregation, which gradually increases over 3-7 days and then reaches a constant level (when an equilibrium state is reached). At steady state, platelet aggregation is suppressed by an average of 40-60%. After discontinuation of clopidogrel, platelet aggregation and bleeding time gradually return to baseline over an average of 5 days. When comparing the pharmacodynamic properties of clopidogrel in men and women, less inhibition of ADP-induced platelet aggregation is observed in women, but no sex differences in prolongation of bleeding time are detected. In patients with recent myocardial infarction, stroke, and diagnosed peripheral arterial occlusive disease, Plavix® 75 mg/day significantly reduces the risk of ischemic complications (combined rate of myocardial infarction, stroke, and cardiovascular death). Moreover, it is most effective in patients with peripheral arterial occlusive disease, especially in combination with a history of myocardial infarction, and is also more effective in patients younger than 75 years;In patients with acute coronary syndrome without ST segment elevation (unstable angina, myocardial infarction) taking Plavix® (loading dose – 300 mg, then 75 mg/day) in combination with acetylsalicylic acid (ASA) (75 – 325 mg once a day) and other standard therapies, regardless of the simultaneous types of treatment (heparin therapy, glycoprotein IIb/Sha blockers, lipid – lowering drugs, beta-blockers, angiotensin converting enzyme (ACE) inhibitors) and from ASA doses, significantly reduces the total risk of ischemic complications: acute myocardial infarction, stroke, and cardiovascular death with a 17% reduction in relative risk with conservative treatment; after percutaneous transluminal coronary angioplasty (PTCA) with or without stenting by 29% and after coronary artery bypass grafting by 10%. In patients with acute myocardial infarction (MI) with ST – segment elevation, taking Plavix® (during the first 12 hours of MI, a loading dose of 300 mg, then 75 mg/day) in combination with ASA (a loading dose of 150-325 mg, then 75-162 mg once a day) and fibrinolytic and, if indicated, with heparin reduces the combined rate of angiography detected at the time of discharge from the hospital of coronary artery occlusion related to the infarction zone, or or recurrent MI; and for patients who did not have angiography performed at discharge, the frequency of death or recurrent MI before the 8th day of MI or before discharge from the hospital, mainly due to a decrease in the frequency of coronary artery occlusion related to the infarction zone. In patients with acute MI with ST-segment elevation, ST-segment decline, or left bundle branch block, taking Plavix ® 75 mg / day in combination with ASA at 162 mg once a day leads to a decrease in the frequency of deaths from any cause and the total frequency of the first recurrent MI, stroke, and deaths.

Indications

Prevention of atherothrombotic complications (in combination with acetylsalicylic acid) in patients with acute coronary syndrome:

• non-ST-segment elevation (unstable angina or non-Q-wave myocardial infarction), including patients who underwent stenting during 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 bleeding from a peptic ulcer or intracranial hemorrhage. Rare hereditary problems of lactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome. Pregnancy and lactation. Children under 18 years of age (safety and efficacy have not been established).

Side effects

Bleeding issues• In the Carpie clinical trial, the overall incidence of all bleeding in patients treated with either clopidogrel or acetylsalicylic acid was 9.3%. The incidence of severe bleeding with clopidogrel was 1.4%, and with acetysalicylic acid -1.6%. In patients treated with clopidogrel and in patients treated with 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 incidence of other bleeding events was higher in patients treated with Clopidogrel than in patients treated with acetylsalicylic acid (7.3% vs. 6.5%, respectively). However, the incidence of severe bleeding was similar in both groups (0.6% vs. 0.4%). Purpura/bruising and nosebleeds were most common in both groups. Less common were hematomas, hematuria, and ocular hemorrhages (mostly conjunctival). The incidence of intracranial hemorrhage was 0.4% in patients treated with clopidogrel and 0.5% in patients treated with acetylsalicylic acid. • In the CURE clinical trial, the use of clopidogrel and acetylsalicylic acid in combination with placebo and acetylsalicylic acid did not lead to a statistically significant increase in the incidence 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 vs. 1.0% – placebo + acetylsalicylic acid) and minor bleeding (5.1% – clopidogrel + acetylsalicylic acid vs. 2.4% – placebo + acetylsalicylic acid). The frequency of intracranial hemorrhages 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 acetylsalicylic acid alone ( 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 acetylsalicylic acid alone, amounting to 9.6% (599/6259) and 6.6% (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 increase in cases of major bleeding within 7 days after this intervention (4.4% – when taking clopidogrel + acetylsalicylic acid versus 5.3% – when taking acetylsalicylic acid alone). 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% (acetylsalicylic acid alone). * In the Clarity clinical trial, there was an overall increase in the frequency of bleeding in the Clopidogrel + acetylsalicylic acid group (17.4%) compared to the placebo + acetylsalicylic acid group (12.9%). The incidence 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 was virtually independent of the initial patient characteristics and the type of fibrinolytic or heparin therapy.The incidence of fatal bleeding (0.8% and 0.6% in the Clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic acid groups, respectively) and intracranial hemorrhage (0.5% and 0.7% in the clopidogrel + acetylsalicylic acid and placebo + acetylsalicylic acid groups, respectively) was low and did not significantly differ in both treatment groups. * In the COMIT 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). Hematological disorders• In the clinical trial Caprie Severe neutropenia (Frequency of severe thrombocytopenia (*In the CURE and Clarity clinical trials, the number of patients with thrombocytopenia or neutropenia in both groups was the same. Other clinically significant side effects. Side effects observed in the clinical trials of CAPRIE, CURE, CLARITY and COMIT with a frequency of > 0.1%, as well as all serious side effects are presented below, according to the WHO classification of side effects. Their frequency is defined as follows: frequent (>1/100,1/1000,1/10000, central and peripheral nervous system disorders: Infrequent: headache, dizziness and paresthesia. Rare: vertigo. Gastrointestinal disorders: Common: diarrhea, abdominal pain, dyspepsia. Infrequently: nausea, gastritis, flatulence, constipation, vomiting, stomach and duodenal ulcers. Hemostatic disorders: Infrequently: prolongation of bleeding time. Blood disorders: Infrequently: thrombocytopenia, leukopenia, neutropenia and eosinophilia. Skin and subcutaneous tissue disorders: Infrequent: rash and itching. Undesirable effects observed in the post-marketing period of clopidogrel alone and in combination with acetylsalicylic acid:Bleeding issues:The most frequent reports of adverse effects were reports of the development of bleeding, which 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 skin tissue hemorrhage (purpura), joint and muscle hemorrhage (hemarthrosis, hematoma), ocular hemorrhage (conjunctival, retinal tissue), nosebleeds, respiratory hemorrhage (hemoptysis, pulmonary hemorrhage), hematuria, and surgical wound bleeding. Patients taking Clopidogrel concomitantly with acetylsalicylic acid or concomitantly with acetylsalicylic acid and heparin have experienced cases of severe bleeding (see “Interactions with other medicinal products” and “Special Instructions”). Other side effects:In addition to the side effects identified in clinical trials and listed above, the following side effects were reported based on spontaneous reports, divided into groups according to the classification of adverse side effects according to organ damage and organ systems presented in the Medical Dictionary for Regulatory Activities 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 (caused by clopidogrel or acetylsalicylic acid). – Thrombocytopenic thrombohemolytic purpura (1:200,000 treated patients), severe thrombocytopenia (platelet count Immune system disorders:- Angioedema, urticaria, anaphylactoid reactions, serum sickness (due to Clopidogrel), anaphylactic shock, aggravation of food allergy symptoms, (due to acetylsalicylic acid). Mental disorders:- Confusion, hallucinations (caused with clopdogrel). Nervous system disorders:- Changes in taste sensations (caused with clopidogrel). Hearing disorders and labyrinth disorders:- Tinnitus, hearing loss (caused by acetylsalicylic acid and usually occurs when it is overdosed). Vascular system disorders:- Vasculitis, low blood pressure (caused by clopidogrel). Respiratory disorders:- Bronchospasm (caused by clopidogrel or acetylsalicylic acid), interstitial pneumonitis (caused with clopidogrel). Disorders of the gastrointestinal tract:- Pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis (caused by clopidogrel). – Ulcer or ulcerative perforation of the stomach or duodenum, symptoms of upper gastrointestinal tract (GI) involvement, such as gastralgia (caused with acetylsalicylic acid). Disorders of the hepatobiliary system:- Acute liver failure, hepatitis (caused by clopidogrel). Skin and subcutaneous tissue disorders – maculopapular or erythematous rash, pruritus, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), eczema and lichen planus (caused by clopidogrel). Musculoskeletal disorders:- Arthralgia, arthritis, myalgia (caused by clopidogrel). Kidney and urinary tract disorders:- Glomerulopathy (due to Clopidogrel), acute renal failure (especially in patients with pre-existing renal failure, heart failure, nephritic syndrome or with simultaneous use of diuretics) (due to acetylsalicylic acid). Metabolic disorders:- Hypoglycemia, gout (caused by acetylsalicylic acid). General violations:- Fever (caused with clopidogrel). Changes in laboratory parameters:- Deviation from the norm of biochemical parameters of the functional state of the liver, an increase in the concentration of creatinine in the blood (due to clopidogrel).

Interaction

Warfarin: concomitant use with clopidogrel may increase the intensity of bleeding, so the use of this combination is not recommended. Glycoprotein IIb/IIIa blockers: the use of glycoprotein IIb/IIIa blockers in combination with clopidogrel requires caution in patients with an increased risk of bleeding (due to injuries and surgical interventions or other pathological conditions).. Acetylsalicylic acid: acetylsalicylic acid does not alter the effect of clopidogrel, which inhibits ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, concomitant use of 500 mg acetylsalicylic acid twice daily for 1 day with clopidogrel did not significantly increase the bleeding time caused by clopidogrel. There may be a pharmacodynamic interaction between clopidogrel and acetylsalicylic acid, which leads to an increased risk of bleeding. Therefore, caution should be exercised when using them simultaneously, 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 in healthy subjects, clopidogrel did not require a change in the dose of heparin and did not change its anticoagulant effect. Concomitant use of heparin did not alter the antiplatelet effect of clopidogrel. There may be a pharmacodynamic interaction between clopidogrel and heparin, which may increase the risk of bleeding, so the simultaneous use of these drugs requires caution. Thrombolytics: The safety of co-use of clopidogrel, fibrin-specific or fibrin-specific thrombolytics, and heparin has been studied in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of combined use of thrombolytics and heparin with acetylsalicylic acid. Nonsteroidal anti-inflammatory drugs (NSAIDs): in a clinical study conducted in 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 not currently known whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel together with other NSAIDs. Therefore, the use of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be carried out with caution.. Other combination therapies Since clopidogrel is metabolized to form its active metabolite in part by the CYP2C19 isoenzyme, the use of drugs that inhibit 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. Concomitant use of strong or moderate CYP2C19 inhibitors (e. g. omeprazole) with clopidogrel should be avoided.. If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the lowest activity of inhibiting the CYP2C19 isoenzyme, such as pantoprazole, should be used.

How to take it, course of use and dosage

Adults and the elderly: Flavix® 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.. Non-ST-segment elevation acute coronary syndrome (unstable angina, non-Q-wave myocardial infarction)Treatment with clopidogrel should begin with a single loading dose of 300 mg, and then continue 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 ST-segment elevation coronary syndrome (acute ST-segment elevation myocardial infarction) Clopidogrel is given once at a dose of 75 mg once a day with an initial single dose of 300 mg in combination with acetylsalicylic acid and thrombolytics (or without thrombolytics). Combination therapy should be initiated as early as possible after the onset of symptoms and continued for at least four weeks. In patients over 75 years of age, treatment with clopidogrel should begin without taking its loading dose. As for the maintenance dose of clopidogrel,75 mg, tablets Plavike® 75 mg are available for its use. Patients with a genetically determined decrease in the function of the CYP2CJ9 isoenzyme, the status of a weak CYP2C19 metabolizer is associated with a decrease in the antiplatelet effect of clopidogrel. A high-dose regimen (600 mg as a 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 for clinical outcomes has not yet been established.

Overdose

Symptoms Overdose of clopidogrel may lead to increased bleeding time with subsequent complications in the form of the development of bleeding. Treatment If bleeding occurs, appropriate treatment measures are required. The antidote of clopidogrel has not been established. If a rapid restoration of the prolonged bleeding time is required, then platelet transfusion is recommended.

Special instructions

Due to the risk of bleeding and hematological undesirable effects (see “Side effects”), if clinical symptoms appear during treatment that are suspicious of the occurrence of bleeding, a clinical blood test should be performed urgently, APTT (activated partial thromboplastin time), platelet count, platelet functional activity indicators should be determined, and other necessary studies should be performed.

Due to the presence of two antiplatelet agents in the composition of Coplavix®, it should be used with caution in patients at increased risk of bleeding due to injuries, surgery or other pathological conditions, as well as in patients receiving nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin, glycoprotein IIB/Sha inhibitors and thrombolytic agents. Patients should be carefully monitored for signs of bleeding, including latent bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures/surgery. Concomitant use of Clopidogrel with warfarin may increase the intensity of bleeding (see “Interaction with other medications”), therefore, with the exception of special rare clinical situations (such as the presence of a floating blood clot in the left ventricle, stenting in patients with atrial fibrillation or other indications for indirect anticoagulants), the combined use of Coplavix and warfarin is not recommended.

If the patient is undergoing elective surgery and there is no need for an antithrombotic effect, then Coplavix® should be discontinued 7 days before the operation. Coplavix ® increases the 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 hemorrhages).

Very rarely, after the use of clopidogrel (sometimes even for a short time), there were cases of thrombocytopenic thrombohemolytic purpura (THP), 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. The combination of acetylsalicylic acid and clopidogrel has been clearly shown to increase the possibility of major bleeding in patients with a recent transient ischemic brain attack or stroke who have an increased risk of recurrent ischemia. Therefore, caution should be exercised when using Coplavix® in such patients in all cases, including those where the beneficial effect of the combination has been proven.

There may be a relationship between acetylsalicylic acid and the occurrence of life-threatening Reye’s 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 from the upper gastrointestinal tract, which may be manifestations of ulcerative lesions of the stomach that can lead to gastric bleeding. During treatment with Coplavix®, upper gastrointestinal symptoms may occur at any time, such as gastralgia, heartburn, nausea, vomiting, and gastrointestinal bleeding. Despite the fact that minor side effects from the gastrointestinal tract, such as dyspeptic disorders, are common during treatment with Coplavix®, the attending physician should always exclude ulceration of the gastrointestinal mucosa and bleeding in these cases, even if there is no history of gastrointestinal pathology.

Patients should be informed about the symptoms of adverse reactions from the gastrointestinal tract. Patients should also be warned that they may take longer than usual to stop bleeding when taking Coplavix®, and that if they experience any unusual (in terms of location or duration) bleeding, they should inform their doctor about this.

Patients should inform their physician (including their dentist) about Coplavix®treatment prior to any upcoming surgery and before starting any new medication. In patients with reduced metabolic function of the CYP2C19 isoenzyme, clopidogrel at the recommended doses produces less of the active metabolite of clopidogrel and reduces its effect on platelet function. Therefore, patients with acute coronary syndrome or undergoing percutaneous coronary intervention and taking clopidogrel may have a higher rate of cardiovascular events than patients with normal function of the CYP2C19 isoenzyme.

This medicine should not be taken by patients with rare hereditary problems of galactose tolerance, lactase deficiency or glucose-galactose malabsorption syndrome (see “Composition”).

Effects on the ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactionsthe ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions is usually not significantly affected by Coplavix®.

However, if the patient experiences adverse side effects from the nervous system and psyche (see the section “Side effects”), it is possible to reduce the concentration of attention and the speed of psychomotor reactions, which may prevent such activities.

In such cases, the question of the possibility of engaging in potentially dangerous activities should be decided by the attending physician.

Storage conditions

Store at a temperature not exceeding 30 °C.

Shelf life

3 years

Active ingredient

: Acetylsalicylic acid, Clopidogrel

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

Prevention of heart attacks and strokes, Prevention of thrombosis