Diloxol

Diloxol is a drug with an antithrombotic effect.

The drug destroys the processes of platelet aggregation, blocking the synthesis of adenosine diphosphate and endings that are located on the platelet membrane, and at the same time activating the glycoprotein endings IIb / IIIa. [1]

The therapeutic agent helps to weaken platelet aggregation associated with the activity of other agonists, and also slows down their activation, which occurs under the influence of the released adenosine diphosphate.

Indications Diloxol

It is used to prevent symptoms of atherothrombosis:

• in persons who have previously suffered a myocardial infarction or an ischemic stroke with an established arterial peripheral disorder (vascular atherothrombosis and arterial lesions of the legs);
• in people with active coronary syndrome: without an increase in ST index (unstable angina and non-Q-infarction), including those who have undergone bypass surgery when performing coronary angioplasty; with an increase in ST values (together with aspirin).

In addition, it is prescribed to prevent atherothrombotic and thromboembolic disorders in atrial fibrillation.

Release form

The release of a medicinal product is sold in the form of tablets - 14 pieces inside a cell package; inside a pack - 1 or 2 such packages.

Pharmacodynamics

Clopidogrel has an effect by irreversibly changing the effect of ADP endings on platelets. Platelets are damaged under the influence of clopidogrel, remaining in this state throughout the entire life cycle; restoration of normal platelet function occurs in accordance with the rate of platelet renewal (about 7 days). [2]

Serving size-related, statistically significant slowing of platelet aggregation develops after 2 hours from the time of administration of a single oral dose of clopidogrel. Reusable doses of 75 mg of drugs significantly inhibit platelet aggregation associated with ADP activity already on the 1st day. This deceleration increases progressively, reaching equilibrium values after 3-7 days. At equilibrium values, the average value of suppression of platelet aggregation, observed at a daily dosage of 75 mg, is 40-60%.

After discontinuation of therapy, platelet aggregation and the duration of bleeding return to the previous level, often after about 1 week.

Pharmacokinetics

With multiple oral doses of 75 mg per day, clopidogrel is rapidly absorbed. Based on the calculation of the urinary excretion of the metabolic elements of clopidogrel, its absorption is less than 50%.

The main circulating decay product has a linear pharmacokinetics (plasma level increases in accordance with the dose size of the drug) within the dosage range of 0.05-0.15 g of clopidogrel.

Most of clopidogrel is involved in intrahepatic metabolic processes. Its main metabolic product, a carboxylic acid derivative, does not alter platelet aggregation. It contains about 85% of compounds similar to the active element circulating inside the plasma. The level of the intraplasmic Cmax of the metabolic element is noted approximately 1 hour after the application of Diloxol.

The above components are reversibly involved in protein synthesis in vitro (by 98 and 94%). It was found that this synthesis is not saturated in large volumes in vitro.

About 50% of the drug is excreted in the urine, and about 46% is excreted in the faeces. The term for the half-life of a metabolic product is 8 hours with a single and multiple dose.

Dosing and administration

Diloxol is taken orally, without reference to food intake. Usually, 75 mg of the drug is taken 1 time per day.

In the case of ACS (with an increase and without an increase in the ST element), therapy begins with a 1-time loading portion of 0.3 g, and then 75 mg is used, 1-fold per day. When combined with aspirin, the likelihood of bleeding increases, which is why dosages of more than 0.1 g should not be used. The maximum therapeutic effect is usually observed after 3 months of therapy.

For people over the age of 75, treatment should be started without consuming the loading portion.

In the case of atrial fibrillation, 75 mg of the drug is taken 1-fold.

• Application for children

It is forbidden to prescribe in pediatrics.

Use Diloxol during pregnancy

Diloxol is not used for breastfeeding and pregnancy.

Contraindications

The main contraindications:

• failure of the liver;
• allergy to clopidogrel;
• hypersensitivity to additional elements of the drug;
• active form of bleeding.

Caution is required when used in persons with chronic renal impairment, hereditary weakening of the activity of the CYP2C19 isoenzyme, or the risk of bleeding. In addition, in people using NSAIDs, heparin, aspirin and substances that inhibit glycoprotein IIb / IIIa.

Side effects Diloxol

Among the side effects:

• changes in blood indications: leuko-, granulocyto-, neutro-, pancyto- and severe thrombocytopenia, eosinophilia, anemia (also aplastic), thrombocytopenic purpura and agranulocytosis;
• immune damage: cross intolerance with thienopyridines (ticlopidine or prasugrel), serum sickness and anaphylactoid symptoms;
• mental problems: hallucinations and confusion;
• neurological disorders: cephalalgia, paresthesias, changes in taste, intracranial bleeding and dizziness;
• ophthalmic disorders: retinal, conjunctival or ocular bleeding;
• otolaryngological lesions: vertigo;
• cardiovascular disorders: vasculitis, decreased blood pressure values, hematoma, wound bleeding after surgery and severe hemorrhage;
• respiratory disorders: bleeding from the nose or lungs, bronchospasm, interstitial pneumonitis, eosinophilic pneumonia and hemoptysis;
• digestive problems: abdominal pain, bloating, bleeding inside the gastrointestinal tract, gastritis, diarrhea, nausea, ulcers and constipation. Bleeding (affecting the gastrointestinal tract or of a retroperitoneal nature), hepatitis, active liver failure, retroperitoneal hemorrhage, pancreatitis, abnormal hepatic function, colitis (lymphocytic or ulcerative type) and stomatitis;
• dermatological lesions: itching, Quincke's edema, hemorrhage under the skin, rashes (also exfoliative), eczema, bullous dermatitis, lichen planus, purpura, urticaria, drug intolerance syndrome and DRESS syndrome;
• dysfunction of ODA: myalgia, arthritis, arthralgia and hemarthrosis;
• disorders of urinary activity: hematuria, glomerulonephritis and an increase in blood creatinine values;
• systemic manifestations: febrile state.

Overdose

Symptoms of poisoning: the appearance of hemorrhagic complications and prolongation of the bleeding period.

It is necessary to stop the resulting bleeding and perform a platelet transfusion procedure.

Interactions with other drugs

It is necessary to carefully combine Diloxol with NSAIDs, as this may increase the likelihood of bleeding inside the gastrointestinal tract.

Tests conducted with human liver microsomes revealed that the drug slows down the activity of the isoenzyme CYP 2C9, which is part of the hemoprotein P450 (2C9) enzyme. As a result, the plasma index of drugs such as tolbutamide or phenytoin may increase, since their metabolic processes proceed with the participation of CYP 2C9.

It is necessary to abandon the combination of the drug with herbal substances (ginkgo biloba, green tea, garlic, ginger, ginseng, medicinal anacyclus, esculus, pubescent uncaria, angelica, two-year-old primrose and red clover), since they have an antithrombotic effect.

Storage conditions

Diloxol should be stored at temperatures between 15-25 ° C.

Shelf life

Diloxol can be used for a 24-month term from the date of sale of the drug.

Analogs

Analogs of the drug are the drugs Arthrogrel, Avix and Areplex with Gridoklein, as well as Agrel and Aterocard.