Warfarex

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

Indications of the warfarex

Applicable in the following cases:

• therapy with prophylaxis for DVT, as well as PE;
• prevention of secondary type in myocardial infarction, and in addition prevention of complications (such as systemic embolism or stroke) after an already happened myocardial infarction;
• prophylaxis of complications of thromboembolic type in people suffering from atrial fibrillation, and in addition defeat of heart valves, or having prosthetic heart valves;
• prevention of stroke or micro stroke.

[1], [2]

Release form

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

[3], [4], [5]

Pharmacodynamics

Warfarin is an anticoagulant, a substance derived from coumarin. Drugs from this category slow down the processes of forming inside the liver of vitamin K in its reconstituted form. This component is required at the final stage of several factors involved in the stabilization of the process of blood coagulation: prothrombin (2nd factor) with proconvertin (7th factor), as well as substances of anti-hemophilic type - globulin B (9th factor) with Stewart- Powers (10th factor), and besides this protein C together with S. As a result, an extension of the period of blood coagulation occurs.

Warfarin has no direct effect on the already formed factors of coagulation within the circulatory system, as a result of which, from the time of drug use inside, it takes about 8-12 hours to develop its effect. The peak of the effect of the medication is on the 2-7th day (during this period the circulating factors inside the blood are excreted from the body).

For a single use, the duration of exposure to the drug is 5 days. Among the isomers of warfarin, the S-warfarin element is about five times stronger than R-warfarin.

[6], [7], [8]

Pharmacokinetics

With the internal reception of drugs, the bioavailability of warfarin is about 90%, and the peak of the plasma level reaches 1.2 hours. Consumption with food slows absorption, but does not reduce its degree (due to the processes of enterohepatic circulation). There are also known processes of enterohepatic recirculation. Most of warfarin is synthesized with the 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 through the placenta, and also in a small amount is excreted with milk.

Metabolism of the substance occurs inside the liver. With the participation of enzymes such as CYP2C9 (this is S-warfarin), and besides CYP1A2 with CYRZA (element R-warfarin), it is converted to inactive decay products excreted from the body with urine. The half-life of the S-warfarin element is 18-35 hours, and the R-warfarin element is 20-70 hours.

[9], [10], [11], [12], [13], [14], [15],

Dosing and administration

Use the medication orally, once a day (recommended at the same time of day). The mode, 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 research indicators. It is forbidden to change the size of the dosage independently or without consultation with the doctor, or stop using the drug.

The size of the initial (first two days) daily dosage is 2.5-5 mg. Further, the dose is gradually selected taking into account the parameters of the person's blood coagulation (MNO). When the required INR (2.0-3.0 or sometimes 3.0-4.5) is reached, the patient is given a new, maintenance dosage.

Weakened or elderly people, and in addition to those who are in the category of risk, initial dosages of a reduced size are prescribed. In addition, care must be taken if they increase. Warfarex is often not used in children.

At the initial stage of the therapy, laboratory monitoring of INR level is carried out daily, then, during the next 3-4 weeks, it is carried out 1-2 times per week, and even later - every 1-4 weeks. The increase in additional control is required when there is a change in the state of health, before performing a planned surgical operation or other procedure, and besides in the case of prescribing / canceling another medication.

[20], [21], [22], [23]

Use of the warfarex during pregnancy

The medicine can not be prescribed to pregnant women, because it has teratogenic properties and can provoke the appearance of bleeding in the fetus, which will lead to its death. It is necessary to carefully weigh the risk of using drugs and evaluate it regarding the risk for a woman in the event of refusal to take Varfarex. Anti-thrombotic treatment during pregnancy should be performed individually, under the constant supervision of a specialist.

Warfarin is able to pass into the mother's milk in small quantities. It does not affect the process of blood coagulation in the baby, because of what the drug is allowed to use during lactation.

Contraindications

The main contraindications:

• intolerance to warfarin or other additional elements of the drug;
• clinically diagnosed bleeding;
• the presence of a tendency to develop bleeding (with violations such as von Willebrand's disease, and in addition thrombocytopenia with thrombocyte activity disorder and hemophilia);
• to prevent the risk of severe forms of bleeding not taken within 72 hours after extensive surgery, and in addition, 48 hours after delivery;
• hepatic cirrhosis, and in addition kidney / liver failure in severe degree;
• uncontrolled or untreated elevated blood pressure;
• recent bleeding of the intracranial type, and in addition states capable of provoking this disorder - among them aortic aneurysm or an aneurysm of the cerebral arteries;
• tendency to fainting;
• surgery on the eyes or in the central nervous system;
• bleeding within the gastrointestinal tract or kidneys, as well as complications of these diseases;
• diverticulosis;
• tumors of malignant type;
• esophageal varices;
• pericarditis (also its exudative form) and infective endocarditis;
• a condition in which the safety of the treatment can not be ensured (eg, in psychoses, dementia or alcoholism);
• lumbar puncture.

[16]

Side effects of the warfarex

The use of tablets can lead to the following side effects:

• manifestations of the disease: development of fever and the appearance of subdural hemorrhage;
• blood flow and hematopoiesis: development of hemorrhage, eosinophilia, coumarin necrosis, and in addition anemia, vasculitis and purpura. In addition, a decrease in hematocrit and the acquisition of a purple hue on the feet;
• disorders in the mediastinum with the sternum and respiratory system: the appearance of hemorachia or calcification within the trachea;
• disorders of the function of the gastrointestinal tract: vomiting (including bloody) with nausea, abdominal pain, diarrhea, melena and bleeding in the rectum or gastrointestinal tract;
• bile duct and liver reactions: a curable increase in hepatic enzyme activity, jaundice and hepatitis of the cholestatic type;
• subcutaneous layers with skin: rash, curable alopecia, itching with urticaria, eczema and puffiness on the skin of the erythematous type, which can cause the development of infarction, cutaneous necrosis, as well as ecchymosis;
• disorders of the function of the urogenital system: development of priapism or hematuria;
• systemic: manifestations of allergy (often in the form of skin rashes), and in addition, urolithiasis, tubular necrosis and nephritis.

Occasionally, there are such side effects: pancreatitis, leukopenia, fever, swelling and itching, and in addition a feeling of weakness, dizziness, lethargic state, headache or abdominal pain, a disorder of taste buds, paresthesia and general microembolization of the substance cholesterol.

[17], [18], [19]

Overdose

Manifestations of chronic poisoning: the appearance of bleeding from the nose or gums, severe menstrual bleeding, and in addition, prolonged or increased bleeding after receiving minor injuries, skin hemorrhage and the presence of blood in feces with urine.

To eliminate weak bleeding, it is required to reduce the dosage of the medicine or to cancel therapy for a short period of time. When heavy bleeding occurs, a freshly frozen plasma is transfused, concentrates of factors entering the prothrombin complex, or whole blood.

[24], [25],

Interactions with other drugs

Warfarex has an interaction with vitamin K. When this element is contained in food products in large quantities, the effectiveness of the drug may be weakened. Antibiotics with a large range of activity inhibit the binding of the vitamin to the intestinal microflora, but the increase in anticoagulant activity in the case of combination with antibiotics occurs rarely, because as with food, the vitamin K enters the body in the required amount.

The delayed effect of the drug on the blood circulation process may increase due to a combination with such substances as urokinase and streptokinase, and in addition heparin with quinidine and methyldopa, as well as amiodarone with diazoxide. It also includes clofibrate and erythromycin, and along with this cefmandol and ethacrynic acid with cefoperazone and chloramphenicol. In addition, such properties are metronidazole and ketoconazole with itraconazole and sulfonamides, as well as nalidixic acid, paracetamol (long-term use in large doses), and fluconazole. In addition, miconazole and aspirin, allopurinol and NSAIDs with propoxyphene and chloral hydrate, as well as sulfinpyrazone and anesthetics, tamoxifen with methylphenidate and danazol. Also included in this list are valproates, and MAO, cimetidine, quinine, thyroid hormone drugs, anabolic and androgenic drugs, glucagon with disulfiram and oral hypoglycemic drugs, and in addition vitamins such as E and A, PASK and the flu vaccine.

Individual drugs that slow platelet aggregation (such as aspirin, other NSAIDs, and in addition ticarcillin with piperacillin and dipyridamole), combined with Warfarex increase the likelihood of bleeding, although the testimony may show a normal prothrombin level.

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

Alcoholic drinks and individual drugs (cyclophosphamide with cholestyramine and disopyramide, as well as phenytoin with glucocorticoids, corticotropin and oral contraception) are able to potentiate and weaken the properties of Warfarex.

[26], [27], [28]

Storage conditions

Warfarex must be kept in a dark place under conditions of a temperature of no more than 25 ° C.

[29], [30], [31]

Shelf life

Warfarex is allowed to be used in the period of 2 years from the date of release of the medicine.

[32]