EGITROMB

Active material: Clopidogrel
When ATH: B01AC04
CCF: Antiplatelet
ICD-10 codes (testimony): I20.0, I21, I63, I73.0, I73.1, I73.9, I79.2
When CSF: 01.12.11.06.01
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)

Pharmaceutical form, composition and packaging

Pills, Film-coated white or nearly white, round, lenticular, Engraved “E 181” on one side, with little or no odor.

Excipients: microcrystalline cellulose and silicon dioxide colloidal anhydrous (silicon microcrystalline cellulose), giproloza (with a low degree of substitution (L-HPC B1)), Castor oil, hydrogenated, opadry white Y-I-7000 (gipromelloza, Titanium dioxide, macrogol 400).

7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

Pharmacological action

antiplatelet agent, specific and active inhibitor of platelet aggregation. Has a coronary dilating effect, selectively reduces the binding of adenosine diphosphate (ADF) receptors on platelets and activation receptor glycoprotein IIb / IIIa by the action of ADP, thus reducing platelet aggregation.

It reduces platelet aggregation, caused by other agonists of these receptors, preventing their activation by free ADP, does not affect PDE activity. It binds irreversibly to platelet ADP receptors, which remain impervious to ADP stimulation lifecycle (about 7 days).

Inhibition of platelet aggregation is a 2 h after administration (40% inhibition of) initial dose. Maximum effect (60% Suppression of aggregation) develops through 4-7 days of admission to the dose of 50-100 mg / day. Antiagregantnyj effect is the entire period of the life of platelets (7-10 days).

In the presence of atherosclerotic lesions of the vessel, it prevents the development of atherothrombosis, regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics

Absorption

Clopidogrel is rapidly absorbed from the gastrointestinal tract after repeated administration of 75 mg / day.

Bioavailability – high. However, the concentration of clopidogrel in plasma is low and after 2 h does not reach the measurement limit (0.025 ug / l).

Distribution

Plasma protein binding – 98-94%.

Metabolism

It is metabolized in the liver. The major metabolite – inactive derivative of a carboxylic acid, T_max which after repeated ingestion in a dose 75 mg achieved through 1 no (C_max – about 3 mg / l).

Deduction

Report the news – 50% and through the intestines with feces – 46% (during 120 hours after injection).

T_1/2 the main metabolite after single and repeated administration – 8 no. Concentrations of renal metabolites – 50%.

Pharmacokinetics in special clinical situations

Concentration of the major metabolite in plasma after ingestion dose 75 mg / day lower in patients with severe renal insufficiency (CC 5-15 ml / min) compared with patients with moderate renal impairment (KK from 30 to 60 ml / min) and healthy individuals.

Testimony

Prevention of ischemic disorders (myocardial infarction, stroke, peripheral arterial thrombosis, sudden vascular death) in patients with atherosclerosis incl.:

— post-myocardial infarction;

- after suffering an ischemic stroke;

- against the background of diagnosed peripheral arterial diseases;

— acute coronary syndrome without ST segment recovery (unstable angina or myocardial infarction without zubza Q) in combination with acetylsalicylic acid;

- in acute myocardial infarction with ST segment elevation in combination with acetylsalicylic acid in patients, receiving conservative treatment, for whom thrombolytic therapy is indicated.

Dosage regimen

The drug is taken orally.

Adults and elderly patients Egithrombus is prescribed according to 75 mg 1 time / day regardless of the meal.

Treatment should begin within the period of a few days before 35 days in patients myocardial infarction and by 7 days before 6 months – patients After ischemic stroke.

At acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without Q wave) taking clopidogrel should be started with a single loading dose 300 mg, and then continue receiving by 75 mg 1 once / day in combination with acetylsalicylic acid (dose 75-325 mg / day). Clinical trial data indicate the possibility of using the drug up to 12 months, and the maximum clinical benefit is noted through 3 of the month.

Acute ST-segment elevation myocardial infarction: Egithrombus should be taken in a dose 75 mg 1 time / day. Treatment should be started with a loading dose and combined with acetylsalicylic acid and thrombolytics or without thrombolytics. Patients over 75 years the course of the drug Egitromb should be prescribed without an initial loading dose. Combination therapy should be read as early as possible after symptoms develop and continued for at least 4 weeks.

Side effect

Determination of the frequency of adverse reactions: often (>1/100, < 1/10); sometimes (>1/1000, < 1/100); rarely (>1/10 000, < 1/1000); rarely (<1/10 000). Within each frequency class, adverse effects are presented in decreasing order of severity..

From the blood coagulation system: common – bleeding (especially often in patients, receiving clopidogrel simultaneously with acetylsalicylic acid, or clopidogrel with acetylsalicylic acid and heparin); sometimes - an increase in bleeding time and a decrease in the number of platelets (thrombocytopenia); rarely – tromboticheskaya trombotsitopenicheskaya purpura (1/200 000 patients, taking the drug).

From the central and peripheral nervous system: sometimes – headache, dizziness, paraesthesia; few – System Vertigo; rarely – confusion, hallucinations, taste disorders.

From the digestive system: often – gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia; sometimes – hemorrhagic stroke, gastric ulcer, duodenal ulcer, gastritis, nausea, vomiting, constipation, flatulence; rarely – pancreatitis, colitis (incl. yazvennыy or limfotsitarnыy colitis), stomatitis, acute liver failure, hepatitis, violations of liver function tests.

Cardio-vascular system: sometimes - arterial hypotension; very rare - vasculitis.

From the hematopoietic system: sometimes – leukopenia, neutropenia and eosinophilia; rarely – tyazhelaya thrombocytopenia (the number of platelets <30 x10⁹/l), agranulocytosis, granulocytopenia, aplastic anemia / pancytopenia. anemia.

Dermatological reactions: sometimes – itching; rarely – bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, eczema, lichen planus.

Allergic reactions: sometimes – skin rash; very rare - urticaria, angioedema, serum sickness, anaphylactoid reactions.

On the part of the respiratory system: rarely – bronchospasm, interstitial pneumonitis.

From the side of the bone-muscular system: rarely – arthralgia, arthritis, myalgia.

From the urinary system: rarely – elevation of serum creatinine, glomerulonephritis.

Other: rarely – fever.

Contraindications

- Severe hepatic impairment;

- active pathological bleeding (peptic ulcer or intracranial hemorrhage);

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years (efficacy and safety have not been proven);

- Hypersensitivity to the drug.

FROM caution the drug should be used in case of moderate hepatic impairment, chronic renal failure, in pathological conditions, increase the risk of bleeding (incl. trauma, operations), simultaneous intake of acetylsalicylic acid, NSAIDs (including COX-2 inhibitors), heparin and glycoprotein IIb/IIIa inhibitors.

Pregnancy and lactation

Clinical data on the use of the drug Egithromb during pregnancy are absent, therefore, clopidogrel should not be prescribed during pregnancy.

There is no information on the excretion of clopidogrel in breast milk in humans., therefore, the use of the drug during lactation is contraindicated.

Cautions

The drug should be used with caution in patients, with an increased risk of bleeding due to injury, surgery, patients, damaged, bleeding prone (especially gastrointestinal and intraocular), and in patients, receiving acetylsalicylic acid, NSAIDs (incl. COX-2 inhibitors), heparin or inhibitors of glycoprotein IIb / IIIa. Patients should be closely monitored for any signs of bleeding., incl. hidden, especially during the first weeks of using the drug and / or after invasive cardiac procedures or surgery. The simultaneous use of clopidogrel and warfarin is not recommended, tk. it can increase bleeding.

During the period of treatment is necessary to monitor the performance of the hemostatic system (APTT, the number of platelets, Platelet function tests); regularly examine the functional activity of the liver.

In the case of surgical procedures, If antiplatelet effect is not desirable, the course of treatment should stop for 7 days before the operation.

Patients should be warned about, that since the stop arising during the use of clopidogrel (with or without acetylsalicylic acid) bleeding takes longer, they should inform the doctor about each case, unusual bleeding. Patients should also inform the doctor about taking the drug., if they have surgery and before taking any new drug.

Thrombotic thrombocytopenic purpura is very rare after taking clopidogrel., sometimes after short-term use. This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological signs, impaired kidney function or fever. Thrombotic thrombocytopenic purpura – potentially fatal condition, requiring immediate treatment, incl. using plasmapheresis.

Due to the lack of data, clopidogrel cannot be recommended for acute (less 7 days) ischemic strokes.

Limited experience with clopidogrel in patients with impaired renal function, therefore, this category of patients should be prescribed with caution..

In severe liver dysfunction, the risk of developing hemorrhagic diathesis should be taken into account.. The experience of using the drug in patients with moderate liver dysfunction is limited., therefore, this category of patients should be prescribed with caution..

Effects on ability to drive vehicles and management mechanisms

The drug does not affect or slightly affects the ability to drive vehicles and work with mechanisms.

Overdose

Symptoms: possible lengthening of bleeding time, which can lead to complications, bleeding.

Treatment: if a rapid reduction in prolonged bleeding time is required, platelet transfusions can reverse the effects of clopidogrel. No antidotes found for the pharmacological activity of clopidogrel.

Drug Interactions

It enhances the antiplatelet effect of aspirin, geparina, thrombolytics, anticoagulants, NSAIDs), It increases the risk of bleeding from the gastrointestinal tract, therefore, the simultaneous use of these funds requires caution.

Clopidogrel should be used with caution in patients, who may be at risk of increased bleeding due to trauma or surgery in case of concomitant use of glycoprotein IIb / IIIa inhibitors.

The simultaneous use of clopidogrel and warfarin is not recommended, tk. in this case, increased bleeding is possible.

There was no clinically significant pharmacodynamic interaction in cases of simultaneous use of clopidogrel with atenolol, nifedipine or combination of atenolol with nifedipine. Besides, the pharmacodynamic activity of clopidogrel did not significantly change with the simultaneous use of phenobarbital, cimetidine or estrogen.

The pharmacokinetics of digoxin or theophylline did not change with the simultaneous administration of clopidogrel.

Antacids do not affect the absorption of clopidogrel.

A study of human hepatic microsomes showed, that the metabolite of clopidogrel, carboxylic acid, can inhibit the activity of the isoenzyme CYP2C9. It can raise plasma levels of drugs such as phenytoin., tolbutamide and NPVS, which are metabolized with the participation of CYP2C9. The use of phenytoin and tolbutamide with clopidogrel is safe.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.