Avix

Avix is prescribed when it is necessary to prevent atherothrombotic manifestations.

Indications of the avix

Aviks are prescribed when it is necessary to prevent atherothrombotic manifestations:

•  patients who underwent myocardial infarction (Avix is prescribed immediately for several days and for thirty-five days), ischemic stroke (treatment is prescribed for a week and for half a year), and if the diagnosis has shown that the peripheral arteries have the disease;
•  patients who have an acute coronary syndrome without lifting the ST segments (the presence of unstable angina or myocardial infarction without a Q wave). This includes patients who underwent stent placement during a procedure such as percutaneous coronary angioplasty, in combination with which acetylsalicylic acid was administered;
•  patients with acute myocardial infarction with ST segment elevation (acetylsalicylic acid in combination) with standard drug treatment if thrombolytic therapy is indicated.

Release form

The drug Avix is available in the form of tablets coated with a film membrane.

Pharmacodynamics

Clopidogrel has a selective inhibition of the binding of adenosine diphosphate (ADP) to its platelet receptor and the next ADP-mediated activation of the GPIIb / IIIa complex, which is why platelet aggregation is inhibited. Biotransformation of clopidogrel is necessary to suppress the aggregation of platelets.

Clopidogrel also helps to suppress platelet aggregation, which is affected by other agonists, by blocking the increase in platelet activation by the released ADP.

Clopidogrel irreversibly modifies the ADP receptors of platelets. Because of this, platelets forever change (as long as an altered batch of platelets continues to exist). The normal function of platelets is restored when they are completely refreshed. With a repeated dose of 75 mg per day from the first day there was a significant inhibition of platelet aggregation, which was caused by ADP. The results were steadily increasing and stabilizing between three days and a week. The stable state was characterized by an average level of depression, which was observed when a dose of 75 mg per day was applied, and was from 40% to 60%. The state of platelet aggregation and the duration of bleeding gradually gained initial values, most often the period was five days after the treatment was canceled.  

Pharmacokinetics

If you take repeated oral doses up to 75 mg, rapid absorption of clopidogrel occurs. But the initial compound is in plasma at a very low concentration, after 2:00 below the threshold of quantification (0.00025 mg / l). As the results of the determination showed, how clopidogrel is excreted in the urine, the body absorbs no less than half of it. The liver extensively metabolizes clopidogrel. In the blood plasma, the main metabolite circulates in an amount of 85% of the compound. This metabolite is a derivative of carboxylic acids, it is not distinguished by activity. Within one hour after taking the drug, a peak level of this metabolite in the blood plasma is observed. The peak level is about 3 mg / L after an oral dose of 75 mg has been introduced). An active metabolite, a thiol derivative, is obtained after oxidizing clopidogrel in 2-oxo-clopidogrel followed by hydrolysis. The oxidation stage is regulated mainly by the isoenzymes 2B6 and 3A4 of cytochrome P450 and slightly less - 1A1, 1A2 and 2C19.

[1]

Dosing and administration

The standard dose of Avix is 75 mg once a day. In acute coronary syndrome without ST segment elevation (the presence of unstable angina or myocardial infarction without a Q wave on the ECG), the first single loading doses are 300 mg, then 75 mg once a day (in addition, acetylsalicylic acid 75-325 mg per day). High doses of acetylsalicylic acid can lead to bleeding, therefore do not recommend taking it in volumes of more than 100 mg. The terms of treatment vary in each specific case, the optimal variant is not established to date. In medical practice, cases where Avix treatment is carried out throughout the year are common, and the maximum effect is reached three months after the first administration of the drug. Patients who have an acute myocardial infarction with ST-segment elevation should take Avix at a dosage of 75 mg during the day, at the beginning - a single 300-mg loading dose along with acetylsalicylic acid (with or without thrombolysis). When the patient is over seventy-five years old, the dose of clopidogrel is not loaded. Combination therapy should be started in the shortest possible time, once the symptoms have been established, its period should be no less than a month. If you combine clopidogrel with acetylsalicylic acid for a given disease for more than a month, the effect of medical practice has not been studied so far. 

[5], [6]

Use of the avix during pregnancy

Today Avix's influence on the course of pregnancy is not investigated by modern science, therefore doctors do not recommend taking this medication while the child is pregnant. The subtleties of the drug in the mother's milk have not been studied, therefore, during the lactation Avix can not be taken. 

Contraindications

Avioks is resistant to the use of:

•  hypersensitivity to the components of the drug;                                       
•  severe hepatic insufficiency;                                                                     
•  acute bleeding (peptic ulcer, intracranial hemorrhage);
•  hereditary intolerance to galactose, Lappease lactase deficiency, glucose-galactose malabsorption;
•  the period of gestation and lactation;                                                                          
•  the drug is contraindicated for children.                                                                                 

[2]

Side effects of the avix

The most common side effect of the drug is the presence of bleeding.

In order to classify the side effects, enter such categories: often (from one time to 100 applications to one to ten), sometimes (from one per thousand receptions to one per hundred), rarely (once for ten thousand receptions - once per thousand), very rarely (once for more than ten thousand receptions).

Side effects of Avix, classified according to different organ systems.

Side effects of Avix on the blood and lymphatic system:

•  It is rare to observe the presence of thrombocytopenia, leukopenia, eosinophilia;
•  rarely occurs neutropenia, as well as severe neutropenia;
•  very rarely - the presence of thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia.

Side effects of Avix on the immune system:

• very rare cases of serum sickness, anaphylactoid reactions.

Among Avic's adverse reactions may be psychiatric disorders:

• very rarely can manifest hallucinations, confusion.

Side effects of Avix on the nervous system:

• infrequent in the patient due to taking the drug may occur intracranial bleeding (in especially rare cases, possible fatal outcome), headache, paresthesia, dizziness;
• very rarely side effects of the drug may manifest itself in a change in taste sensations.  

Side effects of Aviks may appear in eye pathologies:

• infrequently it is possible to meet bleeding in the field of eyeballs (presence of conjunctives, ocular, retinal).

Side effects of Avix in pathologies of the ear and labyrinth:

• rarely there are dizziness.

Side effects of Avix, which lead to vascular disorders:

•  due to the use of the drug, hematomas are frequent;
• very rarely there are significant hemorrhages, bleeding from wounds, vasculitis, arterial hypotension.

Side effects of the drug Aviks - respiratory, thoracic and mediastinal disorders:

• nosebleeds often occur;
• in very rare cases bleeding of the respiratory tract (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonitis is possible.

Side effects of the drug Avix, manifested in violations of the gastrointestinal tract:

• often there are gastrointestinal bleeding, diarrhea, abdominal pain, indigestion
• in the category of "infrequently" note the stomach and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence, etc .;
• rarely - retroperitoneal hemorrhages;
• very rarely possible the presence of gastrointestinal and retroperitoneal bleeding (up to the lethal outcome), pancreatitis, colitis (ulcer or lymphocytic), stomatitis.

Side effects of Avix, affecting the hepatobiliary system:

•  very rarely - manifestations of acute hepatic insufficiency, hepatitis, abnormal results of liver function

Side effects of Avix, affecting the skin and subcutaneous tissue:

• subcutaneous hemorrhages are frequent;
• Rare manifestations of rash, itching, intradermal hemorrhages (purpura);
• very rare occurrence of bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), angioedema, skin rash, urticaria, eczema, flat lichen.

Side effects of Avix, affecting the musculoskeletal system, connective and bone tissue:

• very rarely possible the presence of musculoskeletal hemorrhage (hemarthrosis), arthritis, arthralgia, myalgia.

Adverse effects of Avix, affecting the functioning of the kidneys and urinary system:

• infrequent manifestation of hematuria;
• Very rare manifestations of glomerulonephritis, increasing the level of creatinine in the circulatory system.

Side effects of Avix, manifested in the general state and reactions in the mission introduction:

• manifestations of bleeding at the injection site;
• It is very rare to encounter fever in patients taking Avix.

Side effects of the drug Avix, which had an impact on the conduct of laboratory studies:

• In rare cases, an increase in the time during which bleeding is observed, the number of neutrophils and platelets in the patient's body decreases.

[3], [4]

Overdose

Since the main side effect of the drug Avix is the occurrence of bleeding, an overdose of the drug, and therefore its main active substance - clopidogrel - can cause the effect of increasing the duration of bleeding, as well as the occurrence of subsequent complications. If the drug has caused bleeding, it is necessary to take appropriate measures to eliminate it. To date, no antidote clopidogrel modern medical science is not known. In those situations, if it is necessary to urgently eliminate the prolonged bleeding, it is possible to perform a transfusion of platelet mass, which will lead to the fact that the effect of clopidogrel will decrease. 

Interactions with other drugs

Clopidogrel has a property under the action of CYP2C19 to turn into its active metabolite. Therefore, if you use drugs that reduce the activity of this enzyme, the concentration of the active metabolite of clopidogrel in the plasma will decrease, and accordingly, the clinical efficacy of Avix will decrease.

If the drug leads to suppression of the activity of CYP2C19, then it should not be taken together with Avicom.

Proton pump inhibitors should also not be used simultaneously with Avicom, except in exceptional situations.

To date, the effect on antiplatelet activity of clopidogrel has not been proven to reduce drugs that reduce acid production in the gastrointestinal tract, for example, H2 blockers or antacids.

The action of omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol is to inhibit the activity of CYP2C19.

As for warfarin, vpeste with him is not advised to use clopidogrel, since bleeding due to this can become more intense.

In the situation of IIb / IIIa inhibitors, if patients receive them, the risks of bleeding due to injuries, surgical interventions, or any other pathological conditions increase.

Acetylsalicylic acid does not modify the clopidogrel-mediated inhibition of platelet aggregation, however, due to clopidogrel, the effect of acetylsalicylic acid is increased by collagen-induced platelet aggregation. But when five hundred milligrams of Acetylsalicylic acid were applied twice a day, there was no significant increase in the duration of bleeding due to clopidogrel. Clopidogrel and acetylsalicylic acid can interact pharmacodynamically, in such a situation, acetylsalicylic acid can affect the increased risk of bleeding. Because at the same time to take these two drugs should be very careful.

If clopidogrel is used together with heparin, then there is no need to change the dose of the latter, the modification of the effect of heparin on how blood is clotting does not occur. Clopidogrel and heparin can interact by pharmacodynamics, because of this the risk of bleeding increases. Because these two drugs must also be taken with caution.

When a patient has acute myocardial infarction, if clopidogrel and fibrin-specific or fibrin-nonspecific thrombolytic agents and heparin are used concomitantly, clinically significant bleeding also occurs frequently, as when thrombolytically active agents and heparin are used together with acetylsalicylic acid.

If clopidogrel and naproxen are used concurrently, hidden gastrointestinal bleeding may become more frequent. But the interaction of clopidogrel with other nonsteroidal inflammatory drugs is not well understood, therefore it is not clear to date whether the probability of gastrointestinal inflammations increases if non-steroidal anti-inflammatory drugs are used. Therefore, the use of non-steroidal anti-inflammatory drugs, including COX-2 inhibitors, together with clopidogrel, should be performed cautiously.

Clinically significant pharmacodynamic interactions were not observed with concomitant use of clopidogrel with drugs such as atenolol, nifedipine, or with two of them at once. Moreover, the pharmacodynamics of clopidogrel almost did not change, even when pentobarbital, cimetidine, or estrogens were simultaneously used. There is no change in pharmacokinetics if clopidogrel is used together with digoxin and theophylline. There is no effect on how the clopidogrel is absorbed by the antacids. Suppression of cytochrome P4502C9 activity may be caused by carboxylic metabolites of clopidogrel. There is a potential possibility that the level of plasma levels of phenytoin and tolbutamide, as well as non-steroidal anti-inflammatory drugs, metabolized by P4502C9, increases. Clopidogrel safely combines with phenytoin and tolbutamide.

Specific interactions of clopidogrel, which is part of Avix, we described. Other data on the interaction of clopidogrel with some other drugs that are usually prescribed for the treatment of patients with atherothrombotic disease are not currently available.

There have been quite a number of cases when patients were prescribed a variety of appropriate drug therapy with diuretics, beta-blockers, agiotensin converting enzyme inhibitors, calcium antagonists, cholesterol lowering drugs, coronary vasodilators, antidiabetic drugs (including insulin), antiepileptic drugs, hormone replacement therapy and antagonists of glycoprotein IIb / IIIa, and any clinically relevant adverse interactions Via absent.

[7]

Storage conditions

The drug should be stored away from children, storage temperature 15-30 ºC.

Shelf life

The shelf life of Avix is two years.