Egithromb, 75 mg 28 pcs

Pharmacodynamics

Egithromb is an antiplatelet agent. Specific and active inhibitor of platelet aggregation. Selectively decreases binding of adenosine diphosphate (ADP) to receptors on platelets and activation of GPI IIb/IIIa receptors by ADP, thus weakening platelet aggregation.

Decreases platelet aggregation caused by other agonists by preventing their activation by released ADP, does not affect phosphodiesterase (PDE) activity. It binds irreversibly to platelet ADP receptors, which remain immune to ADP stimulation during the life cycle (about 7 days). Inhibition of platelet aggregation is observed 2 h after administration (40% inhibition) of the initial dose. The maximum effect (60% suppression of aggregation) develops after 4-7 days of continuous administration at a dose of 50-100 mg/day. The antiaggregant effect persists for the entire period of platelet life (7-10 days). In the presence of atherosclerotic vascular lesions it prevents the development of atherothrombosis regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics

Clopidogrel is rapidly absorbed after repeated administration of 75 mg per day. Bioavailability is high. However, the concentration of the initial substance in plasma is low and already after 2 hours does not reach the limit of measurement (0.025 mcg/L). The binding to plasma proteins is 98-94%.

It is metabolized in the liver. The main metabolite is inactive carboxylic acid derivative, TCmax of which after repeated oral doses of 75 mg is reached after 1 hour (Cmax – about 3 mg/L). It is excreted by the kidneys – 50% and through the intestine with feces – 46% (within 120 hours after administration). T½ of the main metabolite after single and repeated administration is 8 hours.

Concentrations of metabolites excreted by the kidneys are 50%. Plasma concentrations of the main metabolite after 75 mg/day administration are lower in patients with severe kidney disease (CK of 5-15 ml/min) compared to patients with moderate kidney disease (CK of 30 to 60 ml/min) and healthy individuals.

Indications

Prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral artery occlusion;

To prevent thrombotic complications in acute coronary syndrome in combination with acetylsalicylic acid (ASA): with ST-segment elevation when thrombolytic therapy is possible; without ST-segment elevation (unstable angina, myocardial infarction without Q-wave), including.including patients undergoing stenting.

Active ingredient

Composition

1 film-coated tablet contains:

the active ingredient:

clopidogrel hydrosulfate 97.86 mg (in terms of clopidogrel – 75 mg);

excipients:

Microcrystalline silica cellulose (MCC, colloidal anhydrous silica);

Hyprolose (low substitution (L-HPC B1);

castor oil hydrogenated;

Opadry white Y-I-7000 (hypromellose, titanium dioxide, macrogol 400)

How to take, the dosage

Adults and elderly patients should take clopidogrel orally 75 mg once daily regardless of meals.

The treatment should be started within a few days to 35 days in patients after myocardial infarction and from 7 days to 6 months in patients after ischemic stroke. In acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without Q-wave), clopidogrel should be started with a single shock dose of 300 mg and then continued with 75 mg once daily in combination with acetylsalicylic acid (ASA 75-325 mg daily).

Interaction

It enhances the antiplatelet effect of acetylsalicylic acid, heparin, thrombolytics, indirect anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), increases the risk of bleeding from the GI tract, therefore concomitant use of these drugs requires caution.

Clopidogrel should be used with caution in patients who may have the risk of increased bleeding during trauma or surgery if glycoprotein IIb/IIIa inhibitors are used concomitantly.

The concomitant use of clopidogrel and warfarin is not recommended, since it may increase bleeding (see also section “Cautions”). No clinically significant pharmacodynamic interactions have been found in cases of concomitant use of clopidogrel with atenolol, nifedipine or combination of atenolol and nifedipine. In addition, pharmacodynamic activity of clopidogrel did not change significantly with concomitant use of phenobarbital, cimetidine or estrogens. Pharmacokinetics of digoxin or theophylline did not change with concomitant administration of clopidogrel. Antacids have no effect on the absorption of clopidogrel. Human hepatic microsomal studies have shown that the carboxylic acid metabolite of clopidogrel can inhibit cytochrome P450 2C9 activity. This can increase plasma levels of drugs such as phenytoin, tolbutamide, and NSAIDs that are metabolized by cytochrome P450 2C9. Phenytoin and tolbutamide can be used safely with clopidogrel.

Special Instructions

During treatment it is necessary to monitor the parameters of the hemostasis system (ABTB, platelet count, tests of platelet functional activity); regular examination of liver functional activity. Clopidogrel should be used with caution in patients with the risk of increased bleeding in trauma, surgery, patients with injuries prone to bleeding (especially gastrointestinal and intraocular), as well as in patients receiving ASA, nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin or glycoprotein IIb/IIIa inhibitors. Patients should be closely monitored for any signs of bleeding, including hidden bleeding, especially during the first weeks of using the drug and/or after invasive cardiac procedures or surgery. Simultaneous use of clopidogrel and warfarin is not recommended, since it may increase bleeding.

In case of surgical interventions, if antiaggregant effect is undesirable, the treatment should be discontinued 7 days before surgery.

Patients should be warned that since it takes longer to stop bleeding when using clopidogrel (with or without ASA), they should inform their physician about each case of unusual bleeding. Patients should also inform their physician about taking the drug if they are going to have surgical interventions and before taking any new medication.

Thrombotic thrombocytopenic purpura (TTP) has been found very rarely after clopidogrel administration, sometimes after short-term use. This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia combined with neurologic signs, impaired renal function or fever. TTP is a potentially fatal condition requiring immediate treatment, including plasmapheresis. Because of the lack of data, clopidogrel should not be recommended for acute (less than 7 days) ischemic strokes. Experience of using clopidogrel in patients with impaired renal function is limited, so these patients should be prescribed with caution. In severe hepatic impairment, remember about the risk of hemorrhagic diathesis, the experience of using the drug in patients with moderate hepatic impairment is limited, so clopidogrel should be prescribed with caution in these patients. Driving ability Clopidogrel has no or negligible effect on the ability to drive vehicles and operate mechanisms.

Contraindications

With caution: moderate hepatic insufficiency, chronic renal insufficiency (CKF), pathological conditions that increase the risk of bleeding (including trauma and surgery).trauma, surgery), simultaneous use of ASA, NSAIDs (including COX-2 inhibitors), heparin and glycoprotein IIb/IIIa receptor inhibitors.

Side effects

Central nervous system disorders: infrequent: headache, dizziness and paresthesia; rare: systemic dizziness; very rare: confusion, hallucinations, taste disorders.

Gastrointestinal tract: frequent: gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia; infrequent: hemorrhagic stroke, gastric ulcer, duodenal ulcer, gastritis, nausea, vomiting, constipation, bloating; very rare: pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis, acute liver failure, hepatitis.

Cardiovascular and hematopoietic system disorders: frequent: hematoma; infrequent: increased bleeding time and decreased platelet count (thrombocytopenia), leukopenia, neutropenia and eosinophilia; very rare: vasculitis, hypotension, thrombotic thrombocytopenic purpura (TTP) (1/200,000 patients taking the drug) (see section “Special Indications”), severe thrombocytopenia (platelet count ≤30 x 109/l), agranulocytosis, granulocytopenia, aplastic anemia/pancytopenia, anemia.

Skin disorders: infrequent: allergic reactions (skin rash), itching; very rare: angioedema, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, urticaria, eczema and lichen planus.

Respiratory system disorders: very rare: bronchospasm, interstitial pneumonitis. Other: very rare: arthralgia, arthritis, myalgia, anaphylactoid reactions, serum sickness, fever, disorders of liver function tests, increased blood creatinine level, glomerulonephritis.

Overdose

Clopidogrel overdose may prolong bleeding time and lead to complications associated with bleeding. If bleeding is detected, appropriate treatment should be administered.

No antidotes to the pharmacological activity of clopidogrel have been identified. If rapid reduction of prolonged bleeding time is necessary, platelet transfusion may eliminate the effects of clopidogrel.

Pregnancy use

Because of the lack of clinical data on the use of the drug in pregnant women, clopidogrel should not be prescribed during pregnancy.

There is no data on excretion in human breast milk, therefore the use of the drug during lactation is contraindicated.

Similarities