Coplavix, 100 mg+75 mg 100 pcs

Coplavix is a prodrug, one of whose metabolites is active and inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to the P2Y12 receptor of platelets and the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex, leading to suppression of platelet aggregation.

The irreversible binding ensures that platelets remain immune to ADP stimulation for the remainder of their lives (approximately 7-10 days), and recovery of normal platelet function occurs at a rate consistent with the rate of platelet renewal. Platelet aggregation caused by agonists other than ADP is also inhibited by blocking the enhanced platelet activation by the released ADP.

Because the formation of the active metabolite occurs via isoenzymes of the P450 system, some of which may be polymorphic or may be inhibited by other drugs, adequate inhibition of platelet aggregation is not possible in all patients. When clopidogrel is taken daily at a dose of 75 mg, significant suppression of ADP-induced platelet aggregation is noted from the first day of administration, which gradually increases over 3-7 days and then reaches a constant level (when equilibrium is reached).

In the equilibrium state platelet aggregation is suppressed by an average of 40-60%. After discontinuation of clopidogrel, platelet aggregation and bleeding time gradually return to baseline within an average of 5 days. When comparing 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 found.

. In patients with recent myocardial infarction, stroke, and diagnosed peripheral arterial occlusive disease, taking Coplavix at a dose of 75 mg/day significantly reduces the risk of ischemic complications (combined rate of myocardial infarction, stroke cardiovascular death and is most effective in patients with peripheral arterial occlusive disease, especially when combined 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), the use of Coplavix (loading dose – 300 mg, then 75 mg/day) in combination with acetylsalicylic acid (ASA) (75 – 325 mg once daily) and other standard therapies regardless of concomitant therapies (heparin therapy, glycoprotein IIb/Sha blockers, hypolipidemic drugs, beta-adrenoblockers, angiotensin-converting enzyme (ACE) inhibitors) and ASA doses, significantly reduces the overall 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 aortocoronary bypass surgery by 10%.

. In patients with acute myocardial infarction (MI) with ST-segment elevation, administration of Coplavix (during the first 12 hours of MI a loading dose of 300 mg, then 75 mg/day) in combination with ASA (loading dose of 150-325 mg, then 75-162 mg once daily) and a fibrinolytic and when indicated, with heparin reduces the combined rate of coronary artery occlusion related to the area of infarction or fatal outcomes or development of recurrent MI detected by angiography at the time of discharge from the hospital; and for patients who did not undergo angiography at discharge, the incidence of death or recurrent MI until day 8 of the MI or until hospital discharge, mainly by reducing the incidence of coronary artery occlusion related to the infarction zone.

In patients with acute MI with ST-segment elevation, ST-segment reduction or left bundle branch block, administration of Coplavix 75 mg/day in combination with ASA 162 mg once daily leads to a reduction in the rate of death from either cause and the cumulative rate of first repeat MI, stroke and fatal outcomes.

Indications

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

without ST segment elevation (unstable angina or non-Q wave myocardial infarction), including patients who underwent stenting for percutaneous coronary intervention;
with ST segment elevation (acute myocardial infarction)

Pharmacological effect

Coplavix is ​​a prodrug, one of whose metabolites 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 remainder of their life (approximately 7-10 days), and restoration of normal platelet function occurs at a rate consistent with platelet turnover. 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 P450 system, some of which may differ in polymorphism or may be inhibited by other drugs, adequate inhibition of platelet aggregation is not possible in all patients. When taking clopidogrel daily at a dose of 75 mg, from the first day of administration there is a significant suppression of ADP-induced platelet aggregation, which gradually increases over 3-7 days and then reaches a constant level (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 returned to baseline levels within an average of 5 days. When comparing the pharmacodynamic properties of clopidogrel in men and women, less inhibition of ADP-induced platelet aggregation was observed in women, but no sex differences in prolongation of bleeding time were detected.

In patients with recent myocardial infarction, stroke and diagnosed peripheral arterial occlusive disease, taking Coplavix at a dose of 75 mg/day significantly reduces the risk of ischemic complications (combined indicator of myocardial infarction, stroke, cardiovascular death, and it is most effective in patients with peripheral artery occlusive disease, especially in combination with infarction history of myocardium, and is also more effective in patients under 75 years of age;

In patients with acute coronary syndrome without ST segment elevation (unstable angina, myocardial infarction), take the drug Coplavix (loading dose – 300 mg, then 75 mg / day) in combination with acetylsalicylic acid (ASA) (75 – 325 mg 1 time per day) and other standard therapies, regardless of concurrent types of treatment (heparin therapy, blockers glycoprotein IIb/IIIa, lipid-lowering drugs, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) and from doses of ASA, significantly reduces the total risk of ischemic complications: acute myocardial infarction, stroke and cardiovascular death with a reduction in the relative risk with conservative treatment by 17%; 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 the drug Coplavix (during the first 12 hours of MI loading dose – 300 mg, then 75 mg / day) in combination with ASA (loading dose 150-325 mg, then 75-162 mg 1 time per day) and a fibrinolytic and, if indicated, with heparin reduces the combined indicator the frequency of occlusion of a coronary artery related to the infarction zone detected during angiography at the time of discharge from the hospital, or deaths, or the development of recurrent myocardial infarction; and for patients who did not undergo angiography at discharge, the incidence of death or recurrent MI before the 8th day of MI or until discharge from the hospital, mainly due to a decrease in the incidence of coronary artery occlusion related to the infarction zone.

In patients with acute MI with ST-segment elevation, ST-segment depression, or left bundle branch block, taking Coplavix 75 mg/day in combination with ASA 162 mg once daily leads to a reduction in the incidence of deaths from any cause and the total incidence of first recurrent MI, stroke, and deaths.

Special instructions

Due to the presence of two antiplatelet substances in the composition of Coplavix®, it should be used with caution in patients at increased risk of bleeding due to trauma, surgery or other pathological conditions, as well as in patients receiving non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin, glycoprotein IIb/IIIa inhibitors and thrombolytic agents.

Active ingredient

Acetylsalicylic acid, Clopidogrel

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 silicon dioxide -0.631 mg,

corn starch -11.111 mg

Pregnancy

Contraindicated.

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 lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Pregnancy and lactation period.

Children under 18 years of age (safety and effectiveness of use have not been established).

Side Effects

Bleeding

Interaction

Warfarin: Concomitant use with clopidogrel may increase bleeding, so the use of this combination is not recommended.

Glycoprotein IIb/IIIa blockers: the use of glycoprotein IIb/IIIa blockers together with clopidogrel requires caution in patients with an increased risk of bleeding (in case of trauma and surgery or other pathological conditions) (see “Special Instructions”).

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, simultaneous administration of acetylsalicylic acid 500 mg 2 times a day for 1 day with clopidogrel did not cause a significant increase in the bleeding time caused by taking 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 alter its anticoagulant effect. Concomitant use of heparin did not change 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 combined use of clopidogrel, fibrin-specific or non-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 observed in the case of combined use of thrombolytic agents and heparin with acetylsalicylic acid.

Nonsteroidal anti-inflammatory drugs (NSAIDs): In a clinical study in healthy volunteers, coadministration of clopidogrel and naproxen increased occult gastrointestinal blood loss. However, due to the lack of interaction studies between clopidogrel and other NSAIDs, it is currently not known whether there is an increased risk of gastrointestinal bleeding when clopidogrel is taken with other NSAIDs. Therefore, the prescription of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be done with caution.

Other combination therapy

Since clopidogrel is metabolized to the formation of its active metabolite in part by the isoenzyme CYP2C19, 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 (eg, omeprazole) with clopidogrel should be avoided. If proton pump inhibitors must be co-administered with clopidogrel, the proton pump inhibitor with the least CYP2C19 inhibitory activity, such as pantoprazole, should be used.

Overdose

An overdose of Clopidogrel can lead to an increase in bleeding time with subsequent complications in the form of bleeding. If bleeding occurs, appropriate treatment is required.

Storage conditions

Store at a temperature not exceeding 30 °C.

Shelf life

3 years.

Manufacturer

Sanofi Winthrop Industries, France