Diloxol

Diloxol is a drug with an antithrombotic effect.

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

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

Indications Diloxol

It is used to prevent symptoms of atherothrombosis:

• in individuals who have previously suffered a myocardial infarction or ischemic stroke with established arterial peripheral disorder (vascular atherothrombosis and arterial lesions of the legs);
• in people with active coronary syndrome: without ST elevation (unstable angina and non-Q-wave infarction), including those who have undergone bypass surgery during coronary angioplasty; with ST elevation (along with aspirin).

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

Release form

The medicinal product is released in the form of tablets - 14 pieces inside a blister pack; inside a pack - 1 or 2 such packs.

Pharmacodynamics

Clopidogrel acts by irreversibly altering the effect of ADP endings on platelets. Platelets are damaged by clopidogrel and remain in this state throughout their life cycle; restoration of normal platelet function occurs in accordance with the rate of platelet renewal (about 7 days). [ 2 ]

A statistically significant dose-related inhibition of platelet aggregation develops within 2 hours of administration of a single oral dose of clopidogrel. Multiple doses of 75 mg of the drug significantly inhibit ADP-related platelet aggregation as early as day 1. This inhibition progressively increases, reaching equilibrium values after 3-7 days. At equilibrium, the average inhibition of platelet aggregation observed with a daily dose of 75 mg is 40-60%.

After discontinuation of therapy, platelet aggregation and bleeding time return to previous levels, often within approximately 1 week.

Pharmacokinetics

Clopidogrel is rapidly absorbed when administered orally at doses of 75 mg/day. Based on urinary excretion of clopidogrel's metabolic components, absorption is less than 50%.

The major circulating breakdown product has linear pharmacokinetics (plasma levels increase with dose size of drug) within the dosage range of 0.05–0.15 g clopidogrel.

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

The above components reversibly participate 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 urine, and another 46% in feces. The half-life of the metabolite is 8 hours with single and multiple doses.

Dosing and administration

Diloxol is taken orally, without regard to food intake. Usually 75 mg of the medicine is taken once a day.

In case of ACS (with or without ST element enlargement), therapy begins with a single loading dose of 0.3 g, and then 75 mg is taken once a day. When combined with aspirin, the risk of bleeding increases, which is why doses greater than 0.1 g should not be used. The maximum therapeutic effect is usually observed after 3 months of therapy.

People over 75 years of age should begin treatment without consuming a loading dose.

In case of atrial fibrillation, 75 mg of the drug is taken once.

• Application for children

It is prohibited to prescribe in pediatrics.

Use Diloxol during pregnancy

Diloxol is not used during breastfeeding and pregnancy.

Contraindications

Main contraindications:

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

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

Side effects Diloxol

Side effects include:

• changes in blood counts: leukopenia, granulocyto-, neutro-, pancyto- and severe thrombocytopenia, eosinophilia, anemia (also aplastic), thrombocytopenic purpura and agranulocytosis;
• immune disorders: cross-intolerance with thienopyridines (ticlopidine or prasugrel), serum sickness and anaphylactoid symptoms;
• mental problems: hallucinations and confusion;
• neurological disorders: cephalgia, paresthesia, taste changes, intracranial bleeding and dizziness;
• ophthalmologic disorders: retinal, conjunctival or ocular hemorrhage;
• otolaryngological lesions: vertigo;
• cardiovascular disorders: vasculitis, decreased blood pressure, hematoma, bleeding from the wound after surgery and severe hemorrhage;
• respiratory disorders: nosebleeds or bleeding from the lungs, bronchospasm, interstitial pneumonitis, eosinophilic pneumonia and hemoptysis;
• Digestive problems: abdominal pain, bloating, gastrointestinal bleeding, gastritis, diarrhea, nausea, ulcers and constipation. Bleeding (gastrointestinal or retroperitoneal), hepatitis, active liver failure, retroperitoneal hemorrhage, pancreatitis, abnormal liver function tests, colitis (lymphocytic or ulcerative type) and stomatitis;
• dermatological lesions: itching, Quincke's edema, subcutaneous hemorrhage, rashes (also exfoliative), eczema, bullous dermatitis, lichen planus, purpura, urticaria, drug intolerance syndrome and DRESS syndrome;
• dysfunction of the musculoskeletal system: myalgia, arthritis, arthralgia and hemarthrosis;
• urinary disorders: hematuria, glomerulonephritis and increased blood creatinine levels;
• systemic manifestations: fever.

Overdose

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

It is necessary to stop the bleeding that has occurred and perform a platelet transfusion procedure.

Interactions with other drugs

Diloxol should be combined with NSAIDs with caution, as this may increase the likelihood of bleeding within the gastrointestinal tract.

Tests conducted with human liver microsomes have shown that the drug inhibits the activity of the CYP 2C9 isoenzyme, which is part of the P450 (2C9) hemoprotein enzyme. As a result, the plasma level of drugs such as tolbutamide or phenytoin may increase, since their metabolic processes involve CYP 2C9.

It is necessary to avoid combining the drug with herbal substances (ginkgo biloba, green tea, garlic, ginger, ginseng, anacyclus officinalis, aesculus, uncaria pubescens, angelica, evening 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 period of 24 months from the date of sale of the drug.

Analogues

Analogues of the drug are the drugs Artrogrel, Avix and Areplex with Gridokline, as well as Agrele and Aterocard.