Coplavix tabs 100mg + 75mg #100

Instruction for Coplavix

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Coplavix is ​​a combined antiplatelet agent.

Release form and composition

Coplavix is produced in the form of film-coated tablets: biconvex, oval, pale pink, engraved with "A100" on one side and "C75" on the other side (7 or 10 pcs. In blisters; in a cardboard box 2 or 4 blisters of 7 pcs., Or 10 blisters of 10 pcs. And instructions for the use of Coplavix).
1 tablet contains:
    active ingredients: clopidogrel hydrogen sulfate (form II) - 97.875 mg (corresponds to clopidogrel in an amount of 75 mg), acetylsalicylic acid - 100 mg;
    additional components: microcrystalline cellulose, macrogol 6000, mannitol, hydrogenated castor oil, colloidal silicon dioxide, low-substituted hyprolose, stearic acid, corn starch;
    film casing: Opadry pink (triacetin, lactose monohydrate, titanium dioxide, hypromellose, iron oxide red dye), carnauba wax.

Pharmacodynamics

Clopidogrel is a prodrug, one of the active metabolites of which is an inhibitor of aggregation (adhesion) of blood corpuscles - platelets. This metabolite is formed during the biotransformation of clopidogrel with the participation of isoenzymes of the cytochrome P450 system. By irreversibly binding to platelet adenosine diphosphate receptors (ADP receptors), the active metabolite of clopidogrel selectively inhibits the binding of ADP to the platelet P2Y12 receptor and further activation of the glycoprotein IIb / IIIa complex (GP IIb / IIIa), as a result of which ADP-induced aggregation is blocked.
Clopidogrel also inhibits platelet aggregation caused by other agonists by blocking their activation by released ADP. Due to the irreversible binding of clopidogrel to platelet ADP receptors, platelets do not respond to ADP stimulation for the rest of their life (approximately 7-10 days), and their normal function is restored at a rate that corresponds to the rate of platelet renewal.
Since the formation of an active metabolite of clopidogrel occurs under the action of isoenzymes of the cytochrome P450 system, and some of them can be polymorphic or suppressed by other drugs, not all patients may have a sufficient blockage of platelet aggregation. From the first day of therapy, with daily use of clopidogrel at a dose of 75 mg, there is a significant inhibition of ADP-induced platelet aggregation, which gradually increases over 3–7 days and, upon reaching an equilibrium state, reaches a constant level. Platelet adhesion in an equilibrium state is inhibited by about 40-60%.
In case of cancellation of Coplavix, its therapeutic effect is noted within 5 days, during this period platelet aggregation and bleeding time gradually return to the initial level.
The antiplatelet effect manifested by acetylsalicylic acid (ASA) differs from the effect of clopidogrel and complements it. ASA inhibits platelet adhesion through irreversible suppression of prostaglandin cyclooxygenase-1 (COX-1), and the resulting decrease in the formation of thromboxane A2, which causes platelet aggregation and vasoconstriction. This effect is observed throughout the life of platelets. Clopidogrel increases the effect of ASA on collagen-induced platelet adhesion. At the same time, ASA does not affect the inhibitory activity of clopidogrel, directed to ADP-induced aggregation.
Both active components of Coplavix, in monotherapy and in combined use, are able to prevent the development of atherothrombosis at any location of atherosclerotic vascular lesions, including its localization in the coronary, cerebral or peripheral arteries.
In the course of clinical trials ACTIVE-A (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events A), it was found that in patients with atrial fibrillation who have at least one risk factor for vascular complications, but unable to be treated with indirect anticoagulants, clopidogrel therapy in combination with ASA, when compared with the use of ASA alone, reduced the incidence of combined myocardial infarction, stroke, systemic thromboembolism outside the vessels of the central nervous system (CNS), or death from vascular causes, largely as a result of reducing the threat of stroke.
This advantage of the combined administration of clopidogrel with ASA was early detected and observed throughout the entire period of the study (up to 5 years). In patients treated with Coplavix, the risk of stroke of any severity decreased, as well as a trend towards a decrease in the incidence of myocardial infarction compared with the group taking ASA in combination with placebo, but there were no differences in the incidence of thromboembolism outside the vessels of the central nervous system or vascular death. In addition, against the background of the use of a combination of clopidogrel with ASA, a decrease in the total number of days of hospitalization due to cardiovascular pathology was recorded.

Pharmacokinetics

After a single and course oral administration of clopidogrel in a daily dose of 75 mg, the substance is rapidly absorbed in the intestine. In blood plasma, the averaged maximum concentrations (Cmax) of unchanged clopidogrel (approximately 2.2–2.5 mg / ml after a single oral dose of 75 mg) are observed on average 45 minutes after taking a single dose. The absorption of the active substance in accordance with the amount of its metabolites excreted by the kidneys is about 50%.
ASA after absorption undergoes hydrolysis with the formation of salicylic acid, Cmax of the latter in the blood plasma is noted 1 hour after taking ASA. After oral administration of Coplavix, due to rapid hydrolysis, after 1.5–3 hours, ASA is practically not detected in the blood plasma.
In vitro, clopidogrel and its main inactive circulating metabolite in the blood reversibly bind to plasma proteins (98% and 94%, respectively). This bond is unsaturated in vitro up to a concentration of 100 mg / l.
ASA is characterized by weak binding to blood plasma proteins and a small volume of distribution (Vd) - 10 liters. Salicylic acid, a metabolite of ASA, has a high degree of binding to blood plasma proteins, but this relationship is nonlinear and depends on the plasma concentration of the substance. At concentrations <100 μg / ml, approximately 90% of salicylic acid binds to blood plasma albumin, it is actively distributed in body fluids and tissues, including in the central nervous system, breast milk, and fetal tissue.
The metabolic transformation of clopidogrel proceeds intensively in the liver. In vitro and in vivo, the active substance is metabolized in two ways. The first pathway is associated with the participation of enzymes (esterases), which leads to hydrolysis and further formation of an inactive metabolite (carboxylic acid derivative), which makes up 85% of the total number of metabolites circulating in the systemic circulation. The second pathway involves the participation of several isozymes of the cytochrome P450 system. Clopidogrel in this case is first converted to 2-oxo-clopidogrel, an intermediate metabolite, from which it is then formed by CYP2C19 and with the participation of some other isoenzymes (including CYP1A2, CYP2B6 and CYP3A4) an active metabolite - a thiol derivative of clopidogrel. This metabolic product was isolated in in vitro studies, it is characterized by rapid and irreversible binding to platelet receptors and inhibits platelet aggregation.
After oral administration of clopidogrel at a loading dose of 300 mg, the Cmax of the active metabolite is 2 times higher than that after using clopidogrel at a maintenance dose of 75 mg for 4 days, while the Cmax of the latter is observed approximately 30-60 minutes after administration.
When used in combination with clopidogrel in blood plasma, ASA rapidly undergoes hydrolysis to salicylic acid with a half-life (T1 / 2) of 0.3–0.4 due to the intake of ASA in doses of 75–100 mg. Salicylic acid undergoes conjugation, mainly in the liver, with the formation of phenolic glucuronide, salicylic acid and acyl glucuronide, as well as a large number of minor metabolites.
Within 120 hours after oral administration of 14C-labeled clopidogrel, about 50% of the radioactivity is excreted by the kidneys, and about 46% through the intestines. After a single oral dose of clopidogrel at a dose of 75 mg, its T1 / 2 is approximately 6 hours. A similar indicator of the main inactive metabolite after a single and course administration of Coplavix is 8 hours.
For salicylic acid, when taking Coplavix, T1 / 2 from plasma is approximately 2 hours. During the metabolism of salicylate, saturable and total clearance decrease against the background of higher serum concentrations due to the limited ability of the liver to form phenolic glucuronide and salicyluric acid. After taking ASA at 10,000–20,000 mg (toxic doses), plasma T1 / 2 may increase up to 20 hours. The rate of elimination of salicylic acid at high doses of ASA depends on the plasma level (corresponds to the kinetics of the zero order), T1 / 2 can be 6 hours or more. The excretion of the unchanged active substance by the kidneys depends on the pH of the urine, with an increase in the latter of more than 6.5, an increase in the renal clearance of free salicylate is noted from <5 to> 80%.
After taking Coplavix in therapeutic doses, about 10% of the administered dose is detected in the urine in the form of salicylic acid, in the form of salicylic acid - 75%, in the form of phenolic glucuronides - 10%, in the form of acyl glucuronides - 5%.
The active and intermediate (2-oxo-clopidogrel) metabolites of clopidogrel are formed by the isoenzyme CYP2C19. Pharmacokinetic parameters and antiplatelet effect of the active metabolite in the study of platelet aggregation ex vivo (study of aggregation in vitro after the metabolism of clopidogrel in the body) depend on the genotype of the isoenzyme CYP2C19. The allele of the CYP2C19 * 1 gene corresponds to fully functional metabolism, and the alleles of the CYP2C19 * 2 and CYP2C19 * 3 genes are non-functional. A decrease in the metabolism of the drug in representatives of the Caucasian (85%) and Mongoloid (99%) races in most cases is caused by the alleles of the CYP2C39 * 3 and CYP2C19 * 2 genes.
Other alleles associated with the absence or weakening of metabolism include the alleles of the genes of isoenzymes CYP2C19 * 4, * 5, * 6, * 7 and * 8, which are less common in the general population. With the existing low activity of the isoenzyme CYP2C19, the patient will have two of the above non-functional alleles of the genes. According to published data, in general populations, the frequency of occurrence of people with low activity of the isoenzyme CYP2C19 is 2% in the Caucasian race, 4% in the Negroid, and 14% in the Mongoloid.
To establish the genotype of the CYP2C19 isoenzyme, appropriate tests are performed.
Given the pharmacokinetics and metabolism of the active substances of Coplavix, clinically significant pharmacokinetic interactions between them are not expected.

Indications for use

Coplavix is ​​indicated for use in adult patients who are already taking clopidogrel and ASA simultaneously to continue treatment for the following purposes:
    secondary prevention of atherothrombotic complications in the presence of acute coronary syndrome (ACS): without ST segment elevation (unstable angina pectoris or myocardial infarction without Q wave), including in patients who underwent stenting during percutaneous coronary intervention; with ST segment elevation (acute myocardial infarction) with drug therapy and the possibility of thrombolysis;
    prevention of thromboembolic and atherothrombotic complications, including stroke, against the background of atrial fibrillation (atrial fibrillation) in the presence of at least one risk factor for the development of vascular complications in patients who cannot carry out indirect anticoagulant therapy and have a low risk of bleeding.

Contraindications

Absolute:
    severe liver failure (over 9 points on the Child-Pugh scale);
    severe renal failure with creatinine clearance (CC) below 30 ml / min;
    acute bleeding, including intracranial hemorrhage and bleeding from a peptic ulcer;
    mastocytosis against which the intake of ASA can provoke severe hypersensitivity reactions, including the development of shock with a decrease in blood pressure, hyperemia of the skin, tachycardia and vomiting (due to the presence of ASA);
    bronchial asthma associated with the intake of salicylates and other non-steroidal anti-inflammatory drugs (NSAIDs); rhinitis syndrome, recurrent nasal / paranasal sinus polyposis and bronchial asthma, hypersensitivity to NSAIDs (due to the ASA component);
    rare hereditary conditions: lactose intolerance due to lactase deficiency; intolerance to galactose; glucose-galactose malabsorption syndrome (because Coplavix contains lactose);
    age under 18;
    pregnancy and lactation;
    hypersensitivity to any of the components of Coplavix.
Relative (requires taking Coplavix tablets with extreme caution):
    moderate degree of liver failure (7-9 points according to Child-Pugh), in which there may be a tendency to bleeding;
    mild and moderate renal failure (CC 30-60 ml / min);
    diseases accompanied by a predisposition to the occurrence of bleeding, especially intraocular, as well as from the gastrointestinal tract (gastrointestinal tract) against the background of gastric ulcer and 12 duodenal ulcer or with indications in the history of gastrointestinal bleeding, with manifestations of disorders of the upper gastrointestinal tract, since this may be due to ulcerative lesions of the stomach, and the drug is able to increase the bleeding time;
    trauma, surgery, including invasive cardiac procedures / surgery;
    a recent transient violation of cerebral circulation or ischemic stroke (against the background of taking Coplavix, the threat of large bleeding increases);
    gout, hyperuricemia (ASA, taken even in low doses, increases the level of uric acid in the blood);
    history of bronchial asthma and allergies (the threat of allergic reactions to ASA is aggravated);
    a genetically determined decrease in the activity of the isoenzyme CYP2C19;
    deficiency of glucose-6-phosphate dehydrogenase (due to the threat of hemolysis);
    a history of allergic and hematological reactions to other thienopyridines (including ticlopidine, prasugrel), due to the possible occurrence of cross-allergic and hematological reactions;
    combined use with NSAIDs (including selective COX-2 inhibitors), heparin, warfarin, glycoprotein IIb / IIIa inhibitors, selective serotonin reuptake inhibitors (SSRIs), thrombolytic agents, methotrexate (at a dose over 20 mg per week), repaxelinide, paclitom, paclit as well as other drugs that are substrates of the isoenzyme CYP2C8, or drugs associated with the risk of bleeding;
    simultaneous reception with ethanol-containing drinks (due to the presence of ASA, the risk of gastrointestinal tract damage is aggravated, and with chronic use of large amounts of ethanol, the threat of bleeding increases).

Coplavix, instructions for use: method and dosage

Coplavix tablets are taken orally once a day. Simultaneous food intake does not affect the effect of the drug.
Recommended dosing regimen for adults and elderly patients with normal activity of the isoenzyme CYP2C19:
    ACS: drug treatment should be started after a single dose of clopidogrel at a loading dose of 300 mg in combination with ASA at doses of 75–325 mg per day, in the form of separate drugs, and in acute myocardial infarction with ST segment elevation - with or without the simultaneous use of thrombolytics them; taking ASA in higher doses can increase the risk of bleeding, therefore, its recommended dose for this indication should not be higher than 100 mg; in patients with ACS without ST segment elevation, the highest positive effect is achieved by the third month of therapy, the optimal duration of treatment has not been officially established, according to clinical studies, taking Coplavix can last up to 12 months; in patients with acute myocardial infarction with ST segment elevation, the course of treatment should be at least 4 weeks; therapy should be started as early as possible after symptoms develop;
    atrial fibrillation: drug treatment should be started after taking clopidogrel at a dose of 75 mg and ASA at a dose of 100 mg in the form of separate drugs.
In patients with a genetically determined reduced level of activity of the isoenzyme CYP2C19, a weakening of the antiplatelet effect of clopidogrel is recorded. To increase the effect of the drug, they are prescribed clopidogrel at a loading dose of 600 mg, and then - daily at 150 mg once a day. However, at present, the optimal dosage regimen of clopidogrel has not been determined for patients in this group in the course of scientific studies that take into account clinical outcomes.

Side effects

The following are clinically significant adverse reactions recorded during five large clinical trials: CURE, CAPRIE, CLARITY, ACTIVE A and COMMIT, as well as with the post-marketing use of a combination of clopidogrel + ASA, or separately clopidogrel and ASA as monotherapy drugs:
    blood and lymphatic system: often - large bleeding¹, life-threatening and requiring transfusion of 4 or more units of action (U) of blood and other bleeding requiring transfusion of 2-3 U of blood; large, non-life-threatening bleeding (the incidence of large non-cerebral / intracranial hemorrhages according to COMMIT studies is infrequent) ¹; minor bleeding (the frequency of development according to ACTIVE-A studies is very common), bleeding at the puncture site of the vessels сосуд, ², hematomas², bruising², leukopenia¹; infrequently - a decrease in the number of platelets in the peripheral blood тяжел, severe thrombocytopenia with the number of platelets in the peripheral blood from 30 to 80 × 109 / L¹, a decrease in the number of neutrophils in the peripheral blood¹, prolongation of bleeding time¹, eosinophilia¹; rarely - neutropenia¹, including in severe form (<0.45 × 109 / l) ¹; life-threatening bleeding with a decrease in blood hemoglobin (Hb) by more than 5 g / dl (the frequency of their occurrence according to CLARITY data is often) ¹; bleeding requiring surgery; intracranial hemorrhages, hemorrhagic strokes (frequency of their occurrence according to CLARITY data - often) ¹; bleeding requiring the use of inotropic agents¹; epistaxis, purpura, hematuria and intraocular hemorrhages, mainly conjunctival, other severe bleeding²; retroperitoneal hemorrhages¹, intraocular hemorrhages with severe visual impairment¹; extremely rare - aplastic anemia¹, severe thrombocytopenia (platelet count in peripheral blood ≤ 30 × 109) ¹; with an unknown frequency * - hemolytic anemia in the presence of insufficiency of glucose-6-phosphate dehydrogenase³, thrombocytopenia³, agranulocytosis², ³; bicytopenia³, anemia¹, aplastic anemia², ³ / pancytopenia², ³, disorders of bone marrow hematopoiesis³, leukopenia³, neutropenia³, acquired hemophilia A², granulocytopenia³, thrombotic thrombocytopenic purpura (TTP) ²; serious cases of bleeding², in most cases of hemorrhages in skin tissue², in muscles, bones, articular cavity, in ocular tissues (conjunctival, retina and internal media of the eye) ², hemoptysis², nosebleeds², bleeding from the respiratory tract², hematuria², operating wound²; intracranial hemorrhage³, including fatal cases predominantly in elderly patients; retroperitoneal hemorrhage and bleeding from the gastrointestinal tract, as well as other cases of fatal bleeding2;
    liver and biliary tract: with unknown frequency * - increased activity of liver enzymes³, hepatitis (non-infectious etiology) ², acute liver failure², chronic hepatitis³, liver damage, mainly hepatocellular³;
    digestive system: often¹ - abdominal pain, dyspepsia, diarrhea, gastrointestinal bleeding; infrequently¹ - constipation, flatulence, nausea, vomiting, gastritis, stomach / duodenal ulcer; with an unknown frequency * - stomatitis², gastralgia³, erosive duodenitis³, esophagitis², colitis², ³ (including ulcerative / lymphocytic) ², erosive gastritis³, ulceration / perforation of the esophagus³, ulcer or perforation of the stomach and / or duodenal ulcer³ small and large intestines³, intestinal perforation³ (these reactions can occur with or without bleeding, and can occur when using any dose of ASA, both with and without gastrointestinal disorders); acute pancreatitis (hypersensitivity reaction to ASA) ³;
    nervous system: infrequently¹ - dizziness, headache, paresthesia; rarely - vertigo¹; with an unknown frequency * - ageusia, changes in taste sensations²;
    mental disorders: with an unknown frequency * - hallucinations², confusion of consciousness²;
    immune system: with unknown frequency * - serum sickness², anaphylactoid reactions², increased food allergy symptoms³, hypersensitivity cross-reactions with other thienopyridines², anaphylactic shock³;
    skin and subcutaneous tissues: infrequently - itching and rash; with unknown frequency * - angioedema2, skin rash (erythematous, maculopapular or exfoliative) ², urticaria ², pruritus ², bullous dermatitis (erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome) ², drug-induced hypersensitivity syndrome with eosinophilia and systemic manifestations) ², acute generalized exanthematous pustulosis ², lichen planus ², eczema ², fixed skin rash (single / multiple skin changes, usually in the form of erythematous plaques of a round / oval shape, arising in the same area with the next admission ) ³;
    cardiovascular system: with unknown frequency * - decrease in blood pressure, vasculitis, ³ (including Shenlein's purpura - Genoch³), Kounis syndrome (allergic myocardial infarction / vasospastic allergic angina pectoris), caused by hypersensitivity to clopidogrel and ASA³;
    musculoskeletal and connective tissue: with unknown frequency * - myalgia², arthritis², arthralgia²;
    kidneys and urinary tract: with an unknown frequency * - glomerulopathy, including glomerulonephritis², renal failure³, acute renal dysfunction (especially with pre-existing renal failure, CHF decompensation, nephrotic syndrome or in patients taking diuretics at the same time) ³;
    respiratory system, chest and mediastinal organs: with unknown frequency * - eosinophilic pneumonia2, interstitial pneumonitis2, bronchospasm2, noncardiogenic pulmonary edema on the background of constant drug intake, associated with a hypersensitivity reaction3;
    metabolism and nutritional disorders: with an unknown frequency * - gout³, hypoglycemia³;
    general disorders: with unknown frequency * - fever²; edema, when taking ASA in daily doses of ≥1.5 g;
    genitals and mammary gland: with unknown frequency * - gynecomastia³;
    hearing organ and labyrinthine disorders: with unknown frequency * - tinnitus³, hearing loss³;
    laboratory and instrumental data: with an unknown frequency * - an increase in the level of creatinine in the blood², a deviation from the norm of the biochemical parameters of the liver function².
¹ violations observed when using a combination of clopidogrel and ASA.
- violations observed with the use of clopidogrel.
³ violations observed when using the ACS.
* according to post-marketing experience of use.

Overdose

Overdose symptoms of clopidogrel may be an increase in bleeding time and further development of bleeding. In this condition, standard measures are prescribed that are used to stop bleeding; the antidote of the substance has not been established. For quick correction of prolonged bleeding, platelet transfusion is possible.
With a moderate degree of overdose of ASA, there may be: ringing in the ears, dizziness, headaches, confusion, nausea, pain in the stomach, vomiting. In the case of severe intoxication, pronounced violations of the acid-base state develop - at first, hyperventilation, leading to the appearance of respiratory alkalosis, followed by respiratory acidosis as a result of the inhibitory effect of the latter on the respiratory center, and metabolic acidosis is also possible. Disorders such as profuse sweating and hyperthermia, leading to dehydration, seizures, restlessness, hallucinations, and hypoglycemia, may occur. Due to the depression of the nervous system, the development of coma, collapse and respiratory arrest is possible. The lethal dose of ASA is 25,000-30,000 mg, the plasma level of salicylate over 300 mg / l (1.67 mmol / l) indicates the presence of intoxication.
Overdose of salicylates, mainly in young children, can cause severe hypoglycemia and fatal poisoning. In acute / chronic overdose of ASA, noncardiogenic pulmonary edema may develop.
In case of a severe overdose, hospitalization is necessary, against a background of moderate - you should try to induce vomiting or perform gastric lavage, then take it orally or introduce an adsorbent and a saline laxative through a tube into the stomach. For the purpose of forced alkalization of urine to accelerate the elimination of salicylates, sodium bicarbonate 250 mmol is injected intravenously for 3 hours with control of acid-base balance and urine pH.
Against the background of severe overdose, treatment with hemodialysis or peritoneal dialysis is preferable. If necessary, symptomatic therapy for other disorders caused by intoxication is prescribed.

Special instructions

In connection with the existing threat of bleeding and hematological side effects when clinical symptoms appear in the course of treatment, indicating the possible development of blood loss, it is urgent to do a clinical blood test, to establish an activated partial thromboplastin time (APTT), the number of platelets in the peripheral blood and indicators of their functional activity, as well as conduct other research.
During the period of therapy, patients should be monitored to identify symptoms of bleeding (including latent), especially during the first weeks of the course, after invasive cardiac procedures and / or surgery.
If the patient is scheduled to undergo a planned surgical operation and there is no need for constant antiplatelet therapy, then Coplavix should be canceled 5-7 days before the surgery.
Patients should be warned that it may take a longer period of time than usual to stop bleeding during treatment with Coplavix, and that they need to inform their doctor about cases of any unusual (in terms of duration or localization) bleeding.
Before carrying out any surgical intervention and before starting concomitant treatment with each new drug, it is required to inform the doctor (including the dentist) about taking Coplavix.
It is extremely rare, after the use of clopidogrel (in some cases, even short-term), the development of TTP was observed, characterized by microangiopathic hemolytic anemia and thrombocytopenia in combination with impaired renal function, neurological disorders and fever. This disease can be life-threatening and requires immediate treatment, including plasmapheresis.
During the reception of clopidogrel, the appearance of acquired hemophilia was sometimes recorded. In the case of a confirmed isolated increase in APTT, with or without the development of bleeding, the possibility of acquired hemophilia should be considered. When the diagnosis is confirmed, it is necessary to discontinue clopidogrel therapy, and, under the supervision of a specialist, receive appropriate treatment.
Against the background of the use of Coplavix, at any time such undesirable reactions from the upper gastrointestinal tract as heartburn, vomiting, nausea, gastralgia and gastrointestinal bleeding may occur. Although dyspeptic disorders are often encountered during therapy, in these cases, the attending physician should exclude ulceration of the gastrointestinal tract mucosa and bleeding, even in the absence of a history of indications of disorders of the digestive tract. Patients should be informed of the symptoms of gastrointestinal adverse reactions and should be instructed to seek immediate medical attention if they occur.

Influence on the ability to drive vehicles and complex mechanisms

Coplavix in most cases does not significantly affect the ability to drive vehicles and other complex equipment. However, when disorders of the psyche and nervous system appear on the background of treatment, the likelihood of a decrease in concentration of attention and the speed of psychomotor reactions increases, which can interfere with engaging in these types of activities. In such cases, the attending physician must decide on the admission of the patient to the performance of potentially hazardous types of work.

Application during pregnancy and lactation

Coplavix is ​​contraindicated during pregnancy.
In the third trimester of pregnancy, the use of Coplavix is contraindicated due to the ASA that is part of it. As a precautionary measure in the I-II trimesters, Coplavix should not be used unless the woman's clinical condition requires taking clopidogrel in combination with ASA. Controlled studies on the use of clopidogrel in pregnant women have not been conducted; in animal studies, its adverse effects on the development of the embryo, pregnancy, childbirth and postnatal development have not been found.
ASA was found to have a teratogenic effect, although it was found that daily doses of substances below 100 mg, which are limitedly used in obstetrics, have demonstrated their safety.
It is not known whether clopidogrel is excreted in breast milk, but it has been established that ASA passes into breast milk. If you need to take Coplavix during lactation, you must stop breastfeeding.

Childhood use

The use of Coplavix in patients under 18 years of age is contraindicated, since the efficacy and safety of its use in children and adolescents has not yet been established.

With impaired renal function

In the presence of severe renal failure (CC below 30 ml / min), treatment with the drug is contraindicated because of the ASA that is part of it.
Patients with mild to moderate renal impairment (CC 30-60 ml / min) should use Coplavix with caution due to insufficient experience.

For violations of liver function

In the presence of severe liver failure (over 9 points on the Child-Pugh scale), drug therapy is contraindicated.
Patients with moderate liver lesions (7-9 points according to Child-Pugh) and a possible tendency to develop hemorrhagic diathesis should take Coplavix with caution due to limited experience of use.

Use in the elderly

In the elderly, changes in the dosage regimen of Coplavix are not required. Patients over 75 years of age with acute ST-segment elevation myocardial infarction should begin therapy with clopidogrel without using a loading dose.

Drug interactions

Medicines, the combined use of which with Coplavix is ​​associated with an increased risk of bleeding due to a possible additive effect (combinations require special care):
    fibrin-specific or non-fibrin-specific thrombolytic agents, heparin: the observed frequency of clinically significant bleeding in patients with acute myocardial infarction was similar to that with the simultaneous use of thrombolytics and. heparin with ASA; clinical data on the combined use of Coplavix and thrombolytic agents are insufficient;
    oral anticoagulants (warfarin): may increase the intensity of bleeding (this combination is not recommended); clopidogrel at a dose of 75 mg did not affect the pharmacokinetic parameters of warfarin and did not change the value of the international normalized ratio (INR) in patients who received warfarin for a long time; however, the risk of bleeding may increase as a result of the independent effect of these substances on hemostasis;
    heparin: no changes in anticoagulant activity were observed, and no dose adjustment of this substance was required in a clinical study; there were no changes in the inhibitory effect of clopidogrel on platelet aggregation; possible aggravation of the threat of bleeding due to potential pharmacodynamic interactions;
    nicorandil: the risk of ulcers and perforations in the gastrointestinal tract and gastrointestinal bleeding increases when this substance is combined with NSAIDs, including ASA and lysine acetylsalicylate;
    inhibitors of glycoprotein Ilb / IIIa: pharmacodynamic interactions may occur;
    SSRIs: platelet activation is impaired and the likelihood of bleeding increases;
    NSAIDs: an increase in latent blood loss through the gastrointestinal tract is possible with the combined use of clopidogrel and naproxen, as a result of this, the combination of Coplavix with NSAIDs, including with COX-2 inhibitors are not recommended; ibuprofen (at a dose of 400 mg with a single dose between 8 hours before or within 30 minutes after taking ASA at a dose of 81 mg) can suppress the effect of low doses of ASA on platelet aggregation, but if it is taken irregularly, it has a clinically significant effect on antiplatelet ASK activity is not expected.
Other possible interaction reactions with the combined use of clopidogrel with the following drugs / agents:
    esomeprazole, omeprazole, fluvoxamine, moclobemide, fluoxetine, voriconazole, ticlopidine, fluconazole, cimetidine, ciprofloxacin, oxcarbazepine, carbamazepine, chloramphenicol (strong and moderate inhibitors of the isoenzyme CYP2C19 is possible, since the CYP2C19 isoenzyme is reduced in the presence of CYP2C19 isoenzyme: the clinical significance of this interaction has not been determined; it is recommended to avoid such combinations;
    CYP2C8 isoenzyme substrates (repaglinide, paclitaxel): there was an increase in systemic exposure of repaglinide, due to the suppression of the CYP2C8 isoenzyme by the glucuronide metabolite of clopidogrel; with these combinations, caution is required;
    proton pump inhibitors (PPIs), which are strong / moderate inhibitors of the isoenzyme CYP2C19 (esomeprazole, omeprazole): this combination is not recommended; if necessary, it is allowed to take Coplavix with PPIs that have a slight effect on the activity of the CYP2C19 isoenzyme (lansoprazole, pantoprazole);
    nifedipine, atenolol: significant pharmacodynamic interaction was observed when;
    digoxin, theophylline: the pharmacokinetic characteristics of these substances did not change;
    cimetidine, phenobarbital, estrogens: no significant effect on the pharmacodynamics of clopidogrel was found;
    tolbutamide, phenytoin (substances metabolized by the isoenzyme CYP2C9); there was no increase in the plasma concentration of these agents in the blood;
    antacids: absorption of clopidogrel did not decrease.
Other possible interaction reactions with the combined use of ASA with the following drugs / agents (combined use should be carried out with caution):
    probenecid, benzbromarone, sulfinpyrazone (uricosuric drugs): suppression of their uricosuric effect is possible;
    metamizole: a decrease in the action of ASA on platelet aggregation is possible;
    methotrexate (at a dose above 20 mg per week): a decrease in its renal clearance is possible, leading to an increase in myelotoxic effect;
    chickenpox vaccine: there have been cases of Reye's syndrome during the period of chickenpox disease after treatment with salicylates; it is not recommended to take salicylates for six months after vaccination against chickenpox;
    acetazolamide: the threat of metabolic acidosis is aggravated;
    valproic acid: the binding of this substance to blood proteins may decrease and its metabolism may be suppressed, and as a result, the total serum concentration of valproic acid and its free fraction may increase;
    anticonvulsants (phenytoin), ACE inhibitors, β-blockers, oral hypoglycemic agents, diuretics: the interaction of these drugs with ASA used in high doses is possible;
    tenofovir: the risk of developing renal failure may be aggravated;
    levothyroxine: it is possible to suppress the binding of thyroid hormones to carrier proteins, leading to a temporary increase in the concentration of free thyroid hormones with a further decrease in their level.
When conducting clinical studies, there was no significant undesirable interaction of clopidogrel and ASA with these drugs: β-blockers, diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), lipid-lowering drugs, slow calcium channel blockers, coronary vasodilators, antiepileptic drugs, antiepileptic drugs ), glycoprotein IIb / IIIa receptor blockers, hormone replacement therapy.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.
Shelf life is 2 years.

Reviews about Coplavix

Patients leave mostly positive reviews about Coplavix, in which they note the effectiveness of the drug when used to prevent atherothrombotic and thromboembolic complications. Coplavix has established itself as a profiling drug after stenting during percutaneous coronary intervention. As advantages, they also point to a convenient dosing regimen and the possibility of a long course of therapy (up to 12 months).
The disadvantages of the remedy include a large list of contraindications and side effects, a long period required to achieve a positive effect from treatment (up to one month), and the high cost of pills.

Terms of sell

You don't need a prescription to buy Coplavix.