Warfarex

Warfarex is an antithrombotic drug that is a vitamin K antagonist.

Indications Warfarex

It is used in the following cases:

• therapy with prophylaxis for DVT, as well as PE;
• prevention of secondary myocardial infarction, as well as prevention of the development of complications (such as systemic embolism or stroke) after a myocardial infarction has already occurred;
• prevention of thromboembolic complications in individuals suffering from atrial fibrillation, as well as heart valve disease, or having prosthetic heart valves;
• prevention of stroke or microstroke development.

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Release form

Release in tablets, 30 pieces inside a container. In a separate package - 1 container with tablets.

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Pharmacodynamics

Warfarin is an anticoagulant, a derivative of the substance coumarin. Medicines from this category slow down the processes of formation of vitamin K in its reduced form in the liver. This component is required at the final stage of several factors involved in stabilizing the blood clotting process: prothrombin (factor 2) with proconvertin (factor 7), as well as antihemophilic substances - globulin B (factor 9) with the Stewart-Power factor (factor 10), and in addition, proteins C together with S. As a result, the blood clotting period is extended.

Warfarin has no direct effect on the already formed coagulation factors in the circulatory system, therefore, from the time of oral administration of the drug until its effect develops, about 8-12 hours must pass. The peak effect of the drug occurs on the 2nd-7th day (during this period, the coagulation factors circulating in the blood are excreted from the body).

With a single use, the duration of action of the drug is 5 days. Among the isomers of warfarin, the element S-warfarin is approximately five times stronger than R-warfarin.

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Pharmacokinetics

When taken orally, the bioavailability of warfarin is about 90%, and the substance reaches its peak plasma level within 1.2 hours. Taking it with food slows down absorption, but does not reduce its degree (due to enterohepatic circulation processes). Enterohepatic recirculation processes are also known. Most of warfarin is synthesized with plasma protein, and the free fraction of the substance is within 0.5-3%.

The distribution volume is approximately 0.14 l/kg. The active component of Warfarex penetrates the placenta and is also excreted in small amounts in milk.

The substance is metabolized in the liver. With the participation of enzymes such as CYP2C9 (this is S-warfarin), and also CYP1A2 with CYP3A (element R-warfarin), it is converted into inactive decay products excreted from the body with urine. The half-life of the element S-warfarin is 18-35 hours, and the half-life of the element R-warfarin is 20-70 hours.

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Dosing and administration

The medicine should be taken orally, once a day (recommended at the same time of day). The regimen, dosage size and duration of the course are prescribed by the doctor individually, taking into account the severity of the pathology, as well as the INR test results. It is prohibited to independently, without consulting a doctor, change the dosage size or stop using the drug.

The initial (first two days) daily dosage is 2.5-5 mg. Then the dosage is gradually adjusted taking into account the blood clotting indices of the person being treated (INR). Upon reaching the required INR value (2.0-3.0 or sometimes 3.0-4.5), the patient is prescribed a new, maintenance dosage.

Debilitated or elderly people, as well as those who fall into the risk category, are prescribed initial dosages of reduced size. In addition, caution is required in case of their increase. Warfarex is often not used in children.

At the initial stage of therapy, laboratory monitoring of the INR level is carried out daily, then, during the next 3-4 weeks, it is carried out 1-2 times a week, and later - every 1-4 weeks. More frequent additional monitoring is required when changes in health are observed, before performing a planned surgical operation or other procedure, and also in the case of prescribing/cancelling another drug.

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Use Warfarex during pregnancy

The drug should not be prescribed to pregnant women because it has teratogenic properties and can provoke the fetus to bleed, which will lead to its death. It is necessary to carefully weigh the danger of using the drug and assess it against the risk to the woman in case of refusal to take Warfarex. Antithrombotic treatment during pregnancy should be carried out individually, under the constant supervision of a specialist.

Warfarin is able to pass into breast milk in small quantities. It does not affect the process of blood clotting in the infant, which is why the drug is allowed to be used during lactation.

Contraindications

Main contraindications:

• intolerance to warfarin or other additional components of the drug;
• clinically diagnosed bleeding;
• the presence of a tendency to develop bleeding (with disorders such as von Willebrand disease, as well as thrombocytopenia with a disorder of platelet activity and hemophilia);
• to prevent the risk of severe bleeding, do not take within 72 hours after major surgeries, and also within 48 hours after childbirth;
• liver cirrhosis, as well as severe renal/liver failure;
• uncontrolled or untreated increase in blood pressure;
• recent intracranial bleeding, as well as conditions that can provoke this disorder - including aortic aneurysm or aneurysm of the cerebral arteries;
• tendency to faint;
• eye or CNS surgeries;
• bleeding inside the gastrointestinal tract or kidneys, as well as complications of these diseases;
• diverticulosis;
• malignant tumors;
• esophageal varices;
• pericarditis (also its exudative form) and infectious endocarditis;
• a condition in which the safety of the treatment cannot be ensured (for example, in cases of psychosis, dementia or alcoholism);
• lumbar puncture.

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Side effects Warfarex

Using the tablets may cause the following side effects:

• manifestations of NS: development of fever and the appearance of subdural hemorrhage;
• reactions of the bloodstream and the hematopoietic system: development of hemorrhage, eosinophilia, coumarin necrosis, as well as anemia, vasculitis and purpura. In addition, a decrease in hematocrit and the acquisition of a purple tint in the toes;
• disorders in the area of the mediastinum with the sternum and the respiratory system: the appearance of hematothorax or calcification inside the trachea;
• gastrointestinal disorders: vomiting (including bloody) with nausea, abdominal pain, diarrhea, melena and bleeding in the rectum or gastrointestinal tract;
• reactions of the biliary tract and liver: treatable increase in the activity of liver enzymes, jaundice and cholestatic hepatitis;
• subcutaneous layers with the skin: rash, curable alopecia, itching with urticaria, eczema and edema of the skin of the erythematous type, which can cause the development of infarction, skin necrosis, and ecchymosis;
• dysfunction of the urogenital system: development of priapism or hematuria;
• systemic: manifestations of allergies (often in the form of skin rashes), as well as urolithiasis, tubular necrosis and nephritis.

Rarely, the following side effects occur: pancreatitis, leukopenia, fever, swelling and itching, as well as a feeling of weakness, dizziness, lethargy, headaches or abdominal pain, taste bud disorders, paresthesia and general microembolization of the substance cholesterol.

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Overdose

Symptoms of chronic poisoning include nosebleeds or bleeding from the gums, heavy menstrual bleeding, prolonged or increased bleeding after minor injuries, skin hemorrhages, and the presence of blood in the feces and urine.

To eliminate minor bleeding, it is necessary to reduce the dosage of the drug or stop therapy for a short period. If severe bleeding occurs, transfusion of fresh frozen plasma, concentrates of factors included in the prothrombin complex, or whole blood is performed.

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Interactions with other drugs

Warfarex interacts with vitamin K. When this element is present in food products in large quantities, the effectiveness of the drug may be weakened. Antibiotics with a wide range of activity suppress the binding of the vitamin to the intestinal microflora, but at the same time, an increase in the activity of the anticoagulant in the case of a combination with antibiotics occurs rarely, because vitamin K enters the body with food in the required amount.

The inhibitory effect of the drug on the blood clotting process may increase due to combination with such substances as urokinase and streptokinase, as well as heparin with quinidine and methyldopa, and amiodarone with diazoxide. These also include clofibrate and erythromycin, as well as cefmandole and ethacrynic acid with cefoperazone and chloramphenicol. In addition, metronidazole and ketoconazole with itraconazole and sulfonamides have such properties, as well as nalidixic acid, paracetamol (long-term use in high doses) and fluconazole. In addition to them - miconazole and aspirin, allopurinol and NSAIDs with propoxyphene and chloralhydate, as well as sulfinpyrazone and anesthetic drugs, tamoxifen with methylphenidate and danazol. Also included in this list are valproates, MAOIs, cimetidine, quinine, thyroid hormone medications, anabolic and androgenic drugs, glucagon with disulfiram and oral hypoglycemic drugs, as well as vitamins E and A, PAS and the influenza vaccine.

Certain drugs that slow down platelet aggregation (aspirin, other NSAIDs, and also ticarcillin with piperacillin and dipyridamole), in combination with Warfarex, increase the likelihood of bleeding, although test results may show a normal prothrombin level.

The anticoagulant effect of the drug may have a weakening effect on nafcillin, griseofulvin with rifampicin, as well as on antacid and diuretic drugs, carbamazepine with ethchlorvinol and barbiturates, as well as on primidone with estrogens, aminoglutemide with glutethimide and ascorbic acid (in high doses).

Alcoholic beverages and certain drugs (cyclophosphamide with cholestyramine and disopyramide, as well as phenytoin with glucocorticoids, corticotropin and oral contraception) can potentiate and weaken the properties of Warfarex.

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Storage conditions

Warfarex must be kept in a dark place at a temperature not exceeding 25 °C.

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Shelf life

Warfarex is permitted to be used for a period of 2 years from the date of release of the drug.

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