Lopirel, 75 mg 14 pcs.

Lopirel is an antiplatelet agent; a specific and active inhibitor of platelet aggregation; has coronarodilator effect. Selectively reduces the binding of ADP. to receptors on platelets and activation of GPI Ib/IIIa receptors under the action of ADP, thereby weakening platelet aggregation. Reduces platelet aggregation caused by other agonists by preventing their activation by released ADP, does not affect FDE activity.

It binds irreversibly to platelet ADP receptors, which remain immune to ADP stimulation throughout the life cycle (about 7 days). Inhibition of platelet aggregation is observed 2 h after administration (40% inhibition) of the initial dose of 400 mg. The maximum effect (60% suppression of aggregation) develops after 4-7 days of continuous dosing 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

Absorption – high; bioavailability – high; plasma concentration is low and does not reach the limit of measurement (0.025 µg/L) 2 h after administration. The binding to plasma proteins is 94-98%.

Metabolized in the liver. The main metabolite is an inactive carboxylic acid derivative, the TcT of which is reached after repeated oral doses of 75 mg in 1 hour (TcT is about 3 mg/L). It is excreted by the kidneys 50%, through the intestine – 46% (within 120 hours after administration).

The T1/2 of the main metabolite after single and repeated administration is 8 hours. Concentrations of metabolites excreted by the kidneys are 50%. Concentration of basic metabolite in plasma after 75 mg/day administration is lower in patients with severe kidney disease (CKR 5-15 ml/min) compared to patients with moderate kidney disease (CKR 30-60 ml/min) and healthy persons.

Indications

Prevention of atherothrombotic events in patients with myocardial infarction, ischemic stroke or with diagnosed peripheral arterial occlusive disease.

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

Active ingredient

Composition

Active ingredient:

clopidogrel hydrosulfate 97.87 mg, corresponding to 75 mg of clopidogrel base;

Associates:

Lactose,

Microcrystalline cellulose,

How to take, the dosage

The drug is taken orally, regardless of meals.

Patients who have had a myocardial infarction, ischemic stroke, or with diagnosed peripheral arterial disease. By 75 mg once a day. Treatment should be started from the first days to day 35 in patients after myocardial infarction and from 7 days to 6 months in patients after ischemic stroke.

Acute coronary syndrome without ST-segment elevation (unstable angina pectoris, myocardial infarction without Q-wave), including patients who underwent stenting during percutaneous coronary intervention. Treatment with Lopirel should be started with a single loading dose of 300 mg and then continued at a dose of 75 mg once daily. (in combination with acetylsalicylic acid). Since the use of acetylsalicylic acid in high doses is associated with an increased risk of bleeding, the recommended dose of acetylsalicylic acid in this indication does not exceed 100 mg. The maximum favorable effect is observed by 3 months of treatment. The course of treatment is up to 1 year.

Patients with acute coronary syndrome with ST-segment elevation (acute myocardial infarction) in combination with acetylsalicylic acid receiving drug therapy with possible use of thrombolytic therapy. Lopirel is administered once at a dose of 75 mg once daily with an initial once-daily loading dose in combination with acetylsalicylic acid and thrombolytics (or without thrombolytics). Combination therapy is started as soon as possible after the onset of symptoms and continued for at least 4 weeks. In patients over 75 years of age, treatment with Lopirel should be started without a loading dose.

Interaction

Warfarin. Concomitant use of clopidogrel with warfarin is not recommended, since this combination may increase the intensity of bleeding.

Glycoprotein IIb/IIIa inhibitors. Administration of glycoprotein IIb/IIIa inhibitors together with clopidogrel requires caution.

Acetylsalicylic acid. Acetylsalicylic acid does not alter the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. Nevertheless, concomitant use of acetylsalicylic acid at a dose of 500 mg twice daily did not cause any significant increase in bleeding time prolonged by clopidogrel. The safety of long-term concomitant use of acetylsalicylic acid and clopidogrel has not been established, but clopidogrel and acetylsalicylic acid can be used simultaneously for up to one year.

Heparin. According to a clinical trial conducted in healthy volunteers, concomitant use of clopidogrel and heparin does not require adjustment of the dose of the latter and does not affect the antiplatelet effect of clopidogrel, but the safety of this combination has not yet been established and the simultaneous use of these drugs requires caution.

Trombolytic agents. The safety of concomitant use of clopidogrel with thrombolytics is currently not established; therefore, the concomitant use of these drugs requires caution.

Non-steroidal anti-inflammatory drugs (NSAIDs) . In a clinical trial with healthy volunteers, coadministration of clopidogrel and naproxen increased the number of hidden gastrointestinal bleeds. However, due to the lack of drug interaction trials with other NSAIDs, it is currently not determined whether there is an increased risk of gastrointestinal bleeding when using other drugs in this group. Thus, the combined use of NSAIDs and clopidogrel requires caution.

Other drug combinations. No clinically significant pharmacodynamic interaction was found when using clopidogrel together with atenolol and/or nifedipine. Pharmacodynamic activity of LOPIREL practically does not change when used concomitantly with phenobarbital, cimetidine or estrogens. Pharmacokinetic properties of digoxin or theophylline do not change when used together with clopidogrel. Antacids do not alter absorption of clopidogrel.
Data obtained in studies with human liver microsomes suggest that clopidogrel may inhibit the activity of one of the enzymes of cytochrome P450 (CYP 2C9). As a result, plasma levels of some drugs, such as phenytoin and tolbutamide, may be elevated because they are metabolized through CYP 2C9. The results of the CAPRIE study suggest that it is safe to use phenytoin and tolbutamide together with clopidogrel.

Contraindications

Hypersensitivity, hemorrhagic syndrome, acute bleeding, intracranial hemorrhage and diseases predisposing to their development (acute gastric and duodenal ulcer, non-specific ulcerative colitis, tuberculosis, lung tumors, hyperfibrinolysis), severe liver failure; for dosage forms containing lactose (optional): hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Side effects

Nervous system and sensory organs: fatigue, asthenia, headache, dizziness, paresthesia, leg cramps, hyperesthesia, neuralgia, cataract, conjunctivitis.

Cardiovascular system and blood (hematopoiesis, hemostasis): peripheral edema, arterial hypertension, heart failure, generalized edema, syncope, palpitation, thrombocytopenia, anemia (aplastic or hypochromic), agranulocytosis, leukopenia, neutropenia.

Coagulation disorders and bleeding: Purpura, extravasation, epistaxis, gastrointestinal bleeding, joint bleeding, urinary tract bleeding, hemoptysis, intracranial bleeding, retroperitoneal bleeding, bleeding from an operating wound, intraocular bleeding, hemothorax, pulmonary bleeding, allergic purpura, thrombocytopenic thrombohemolytic purpura.

Gastrointestinal organs: abdominal pain, dyspepsia, diarrhea, nausea, vomiting, constipation, taste disorders, stomach ulcer perforation, hemorrhagic gastritis, upper GI ulcer bleeding, increased liver enzyme activity, hyperbilirubinemia, hepatitis, liver steatosis.

Musculoskeletal system disorders: arthralgia, back pain, arthritis, arthrosis.

Respiratory system: inflammation of the upper respiratory tract, shortness of breath, rhinitis, bronchitis, cough, pneumonia, sinusitis.

Treatment of the urinary system: urinary tract infections, cystitis, menorrhagia.

Skin disorders: rash, itching, eczema, skin ulcers, bullous dermatitis, erythematous rash, maculopapular rash, urticaria.

Others: chest pain, injuries, flu-like symptoms, pain. Single cases of hemolytic uremic syndrome, membranous nephropathy and hypersensitivity reactions (angioedema, bronchospasm, anaphylactic reactions) have been reported.

Pregnancy use

Lopirel is contraindicated in pregnancy and lactation.

Similarities