Avix

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

Indications Avixa

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

• patients who have had a myocardial infarction (Avix is prescribed immediately for several days and for thirty-five days), ischemic stroke (treatment is prescribed for a week and for six months), and also if diagnostics have shown that the peripheral arteries have a disease;
• patients with non-ST-segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction). This also includes patients who have undergone stent placement during a procedure such as percutaneous coronary angioplasty, in combination with acetylsalicylic acid;
• patients who have experienced acute myocardial infarction with ST segment elevation (acetylsalicylic acid in combination) during standard drug treatment, if thrombolytic therapy is indicated.

Release form

The drug Avix is available in the form of film-coated tablets.

Pharmacodynamics

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and subsequent ADP-mediated activation of the GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to inhibit platelet aggregation.

Clopidogrel also inhibits platelet aggregation, which is affected by other agonists, by blocking the enhancement of platelet activation by released ADP.

Clopidogrel irreversibly modifies the ADP receptors of platelets. Because of this, the platelets are permanently changed (as long as the altered batch of platelets continues to exist). Normal platelet function is restored when they are completely renewed. With a repeated dose of 75 mg per day, significant inhibition of platelet aggregation caused by ADP occurred from the first day. The results steadily increased and stabilized between three days and a week. Steady state was characterized by an average level of inhibition, which was observed when a dose of 75 mg per day was used, and ranged from 40% to 60%. The state of platelet aggregation and bleeding time gradually returned to baseline values, most often within five days after the treatment was discontinued.

Pharmacokinetics

Clopidogrel is rapidly absorbed after repeated oral doses of up to 75 mg. However, the parent compound remains in plasma at very low concentrations, below the quantification threshold (0.00025 mg/L) after 2 hours. As shown by the results of clopidogrel urinary excretion, at least half of it is absorbed by the body. The liver extensively metabolizes clopidogrel. The main metabolite, accounting for 85% of the compound, circulates in plasma. This metabolite is a carboxylic acid derivative and is inactive. Peak plasma levels of this metabolite occur within one hour after administration. The peak level is approximately 3 mg/L after an oral dose of 75 mg has been administered. The active metabolite, a thiol derivative, is obtained after oxidation of clopidogrel to 2-oxo-clopidogrel, followed by hydrolysis. The oxidation stage is regulated mainly by cytochrome P450 isoenzymes 2B6 and 3A4 and, to a lesser extent, by 1A1, 1A2 and 2C19.

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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 are taken once a day (in addition, acetylsalicylic acid 75 - 325 mg per day). High doses of acetylsalicylic acid can lead to bleeding, so it is not recommended to take it in volumes greater than 100 mg. The duration of treatment varies in each specific case; the optimal option has not been established to date. In medical practice, there are common cases when treatment with Avix lasts for a year, and the maximum effect is achieved three months after the first dose of the drug. Patients with acute ST-segment elevation myocardial infarction should take Avix 75 mg daily, initially a single loading dose of 300 mg with acetylsalicylic acid (with or without thrombolytics). When the patient is over seventy-five years old, the loading dose of clopidogrel is not used. Combination therapy should be started as soon as possible after symptoms have been established, and its duration should be at least one month. If clopidogrel is combined with acetylsalicylic acid for more than a month in this disease, the effect has not yet been studied in medical practice.

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Use Avixa during pregnancy

Today, the effect of Avix on the course of pregnancy has not been studied by modern science, so doctors do not recommend taking this drug during pregnancy. The subtleties of the drug getting into the mother's milk have not been studied, so Avix should not be taken during lactation either.

Contraindications

Contraindications to the use of the drug Avix are the presence of:

• hypersensitivity to the components of the drug;
• severe liver failure;
• acute bleeding (peptic ulcer, intracranial hemorrhage);
• hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption;
• the period of bearing a child and lactation;
• The drug is contraindicated for children.

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Side effects Avixa

The most common side effect of the drug is bleeding.

In order to classify side effects, the following categories are introduced: often (from once in 100 applications to once in ten), sometimes (from once in a thousand applications to once in a hundred), rarely (once in ten thousand applications – once in a thousand), very rarely (once in more than ten thousand applications).

Side effects of Avix, classified by different organ systems.

Side effects of Avix on the blood and lymphatic system:

• rarely, thrombocytopenia, leukopenia, and eosinophilia can be observed;
• neutropenia is rare, as is severe neutropenia;
• very rare – the presence of thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia.

Side effects of Avix on the immune system:

• Cases of serum sickness and anaphylactoid reactions are very rare.

Side effects of Avix may include psychiatric disorders:

• very rarely, hallucinations and confusion may occur.

Side effects of Avix on the nervous system:

• rarely, as a result of taking the drug, the patient may experience intracranial bleeding (in extremely rare cases, a fatal outcome is possible), headache, paresthesia, dizziness;
• very rarely, side effects of the drug may manifest themselves in changes in taste sensations.

Side effects of the drug Avix may manifest in eye pathologies:

• It is not common to see bleeding in the area of the eyeballs (presence of conjunctiva, ocular, retinal).

Side effects of Avix in ear and labyrinth pathologies:

• dizziness is rare.

Side effects of Avix that lead to vascular disorders:

• as a result of taking the drug, hematomas are common;
• Very rarely, significant hemorrhages, bleeding from wounds, vasculitis, and arterial hypotension occur.

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

• nosebleeds are common;
• In very rare cases, respiratory tract bleeding (hemoptysis, pulmonary hemorrhage), bronchospasm, and interstitial pneumonitis are possible.

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

• Gastrointestinal bleeding, diarrhea, abdominal pain, and dyspepsia are common
• in the “infrequently” category, stomach and duodenal ulcers, gastritis, vomiting, nausea, constipation, flatulence, etc. are noted;
• rarely - retroperitoneal hemorrhages;
• very rarely, gastrointestinal and retroperitoneal bleeding (even fatal), pancreatitis, colitis (ulcerative or lymphocytic), and stomatitis may occur.

Side effects of the drug Avix that affect the hepatobiliary system:

• very rare - manifestations of acute liver failure, hepatitis, abnormal results of liver function tests

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

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

Side effects of the drug Avix that affect the musculoskeletal system, connective and bone tissue:

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

Side effects of the drug Avix that affect the functioning of the kidneys and urinary system:

• hematuria is rare;
• manifestations of glomerulonephritis and increased levels of creatinine in the circulatory system are very rare.

Side effects of the drug Avix, manifested in the general condition and reactions during the administration mission:

• Bleeding at the injection site is common;
• It is very rare to see fever in patients taking Avix.

Side effects of the drug Avix that affected laboratory tests:

• in rare cases, the time during which bleeding occurs may increase, and the number of neutrophils and platelets in the patient's body may decrease.

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Overdose

Since the main side effect of Avix is bleeding, an overdose of the drug, and therefore its main active substance - clopidogrel - can cause an effect of increasing the duration of bleeding, as well as the occurrence of subsequent complications. If taking the drug caused bleeding, it is necessary to take appropriate measures to eliminate it. To date, no antidote to clopidogrel is known to modern medical science. In those situations, if it is necessary to urgently eliminate prolonged bleeding, a platelet transfusion can be performed, which will lead to the fact that the effect of clopidogrel will decrease.

Interactions with other drugs

Clopidogrel has the property of being transformed into its active metabolite under the influence of CYP2C19. Therefore, if drugs that reduce the activity of this enzyme are used, the concentration of the active metabolite of clopidogrel in plasma will decrease, and accordingly, the clinical efficacy of Avix will decrease.

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

Proton pump inhibitors should also not be used concomitantly with Avix, except in exceptional situations.

To date, there is no evidence that drugs that reduce acid production in the gastrointestinal tract, such as H2 blockers or antacids, affect the antiplatelet activity of clopidogrel.

Omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol act by inhibiting CYP2C19 activity.

As for warfarin, it is not recommended to use clopidogrel with it, as it may cause more intense bleeding.

In the case of IIb/IIIa inhibitors, if patients receive them, the risks of bleeding due to trauma, surgery, or any other pathological conditions increase.

Acetylsalicylic acid does not modify clopidogrel-mediated inhibition of platelet aggregation, however, clopidogrel increases the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, when five hundred milligrams of acetylsalicylic acid were used simultaneously twice a day, there was no significant increase in the duration of bleeding due to clopidogrel. Clopidogrel and acetylsalicylic acid may interact pharmacodynamically, in which case acetylsalicylic acid may affect the increased risk of bleeding. Therefore, these two drugs should be taken simultaneously with extreme caution.

If clopidogrel is used together with heparin, there is no need to change the dose of the latter, there is no modification of the effect of heparin on how blood clots. Clopidogrel and heparin can interact in pharmacodynamics, because of this the risk of bleeding increases. Therefore, these two drugs should be taken simultaneously with caution.

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

When clopidogrel and naproxen are used simultaneously, occult gastrointestinal bleeding may increase. However, the interaction of clopidogrel with other nonsteroidal anti-inflammatory drugs has not been sufficiently studied, so it is currently unclear whether the likelihood of gastrointestinal inflammation increases when nonsteroidal anti-inflammatory drugs are used. Therefore, the use of nonsteroidal anti-inflammatory drugs, including COX-2 inhibitors, together with clopidogrel should be carried out with caution.

No clinically significant pharmacodynamic interactions have been observed when clopidogrel is co-administered with atenolol, nifedipine, or both. Furthermore, the pharmacodynamics of clopidogrel are largely unchanged even when phenobarbital, cimetidine, or estrogens are co-administered. There are no changes in the pharmacokinetics of clopidogrel when co-administered with digoxin and theophylline. There is no effect of antacids on the absorption of clopidogrel. Inhibition of cytochrome P4502C9 activity may be caused by carboxyl metabolites of clopidogrel. There is a potential for increased plasma levels of phenytoin and tolbutamide, as well as nonsteroidal anti-inflammatory drugs metabolized by P4502C9. Clopidogrel is safely combined with phenytoin and tolbutamide.

We have described specific interactions of clopidogrel, which is part of Avix. Other data on the interaction of clopidogrel with some other drugs that are commonly prescribed to treat patients with atherothrombotic disease are currently lacking.

There have been many cases in which patients have been prescribed a variety of appropriate drug therapies with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, cholesterol-lowering drugs, coronary vasodilators, antidiabetic drugs (including insulin), antiepileptic drugs, hormone replacement therapy and glycoprotein IIb/IIIa antagonists, and no clinically significant adverse interactions have been observed.

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Storage conditions

The drug should be stored out of reach of children at a storage temperature of 15-30 ºС.

Shelf life

The shelf life of the drug Avix is two years.