Warfarin

General characteristics. Structure:

Active agent: warfarin of sodium of 2,50 mg;

excipients: hydrophosphate calcium dihydrate, cellulose microcrystallic, silicon dioxide colloid (aerosil), коповидон (пласдон Es-630). croscarmellose sodium (primelloza), magnesium stearate.

Description: tablets of color, white or white with a yellowish shade, biconvex from crosswise risky.

Pharmacological properties:

Pharmacodynamics. Anticoagulant of indirect action. Vitamin of K-dependent blood-coagulation factors suppresses in a liver synthesis (П, VII, IX and X) and proteins C isv a liver. Optimachny anticoagulating action is observed for 3–5 day from the beginning of use and stops in 3–5 days after reception of the last dose.

Pharmacokinetics. After intake warfarin is completely absorbed in the digestive tract (DT). Communication with proteins of a blood plasma — 97–99%. Therapeutic concentration in plasma of-1-5 mkg/ml (0.003–0.015 mmol/l). Is in a type of racemic connection, at the same time in an organism chelovekal-isomer has bigger activity, than dextrorotatory. Gets through a placenta, but does not cosecrete with breast milk.

Drug is metabolized in a liver with formation of inactive and slaboaktivny metabolites which reabsorbirutsya from bile, at etoml-isomer is metabolized quicker. An elimination half-life of racemic warfarin — 40 h. It is removed by kidneys.

Indications to use:

Treatment and prevention of thrombosis and thromboembolism of vessels: acute venous thrombosis and thromboembolism of a pulmonary artery; postoperative thrombosis; repeated myocardial infarction; as the additional medicine (M) when performing surgical or thrombolytic treatment of thrombosis, and also at electric cardioversion of a ciliary arrhythmia; recurrent venous thrombosis; repeated thromboembolism of a pulmonary artery; prosthetics of valves of heart and vessels (the combination with acetylsalicylic acid (ASK) is possible; thrombosis of peripheral, coronary and brain arteries; secondary prevention of thrombosis and thromboembolism after a myocardial infarction and at atrial fibrillation.

Route of administration and doses:

Inside, in one step, at the same time days.
Initial dose — 2.5–5 mg/days. The further mode of dosing is set individually depending on results of definition of a prothrombin time or the international normalized relation (MHO). The prothrombin time has to be increased by 2–4 times from initial, and MHO has to reach 2.2–4.4 depending on a disease, danger of thrombosis, risk of development of bleedings and specific features of the patient.

When determining MHO it is necessary to consider an index of sensitivity of thromboplastin and to use this indicator as a correction factor (1.22 — when using domestic thromboplastin from a brain of a rabbit of "Neoplast" and 1.2 — when using thromboplastin of Roche Diagnostika).

The elderly and weakened patient usually appoint lower doses of drug. Передпредстоящимхирургическимвмешательством (privysoky risk of tromboembolic episodes) treatment is begun in 2–3 days prior to operation. In case of acute thrombosis treatment is carried out to combinations with heparin until until the effect of peroral anticoagulating therapy completely is shown (not earlier than on 3–5 days of treatment).

At prosthetics of valves of heart, an acute venous vein thrombosis or a thromboembolism (at the initial stages), fibrinferment of a left ventricle and for prevention of ischemia of a myocardium needs to aim at the effective action which is noted at MHO-2.8–4.5. In case of atrial fibrillation and when carrying out a maintenance therapy at a vein thrombosis and a thrombembolia try to obtain moderate anticoagulative effect (MHO 2.8–3). At combined use of warfarin with ASK the indicator of MHO has to be in limits 2–2.5.

Duration of treatment depends on a condition of the patient. Treatment can be cancelled at once.

Features of use:

Before therapy define MHO indicator (according to a prothrombin time taking into account coefficient of sensitivity of thromboplastin). Further carry out regular (each 2–4–8 weeks) laboratory control. During treatment it is necessary to abstain from the ethanol use (risk of development of a prothrombinopenia and bleedings).

Side effects:

Most often — bleeding. Seldom — diarrhea, increase in activity "hepatic" az's Transaminum. eczema, skin necrosis; vasculites, hair loss.

Interaction with other medicines:

Non-steroidal anti-inflammatory drugs (NPVP). Dipiridamolum, valproic acid, P450 cytochrome inhibitors (Cimetidinum, chloramphenicol) increase risk of development of bleedings. It is necessary to avoid the combined use of these HP and warfarin (Cimetidinum can be replaced with ranitidine or famotidine). In need of treatment by chloramphenicol anticoagulating therapy should be stopped temporarily. Diuretics can reduce effect of anticoagulants (in case of the expressed hypovolemic action which can lead to increase in concentration of blood-coagulation factors).

Weaken action: barbiturates, vitamin K, глутетимид, griseofulvin, диклоксациллин, carbamazepine, миансерин, paracetamol, retinoids, rifampicin. сукральфат, phenazone, Colestyraminum.

Strengthen: Allopyrinolum, Amiodaronum, anabolic steroids (alkylated in situation C17), ASK and other NPVP, heparin, glibenclamide, a glucagon, даназол, diazoxide, Disopyramidum, Disulfiramum, an isoniazid, кетоконазол, кларитромицин, Clofibratum, levamisole, metronidazole, Miconazolum, Acidum nalidixicum, нилутамид, омепразол, пароксетин, proguanil. peroral hypoglycemic HP — derivatives of streptocides, симвастатин, streptocides, Tamoxifenum. thyroxine, quinine, quinidine. флувоксамин, флуконазол, ftoruratsit, hinolona, Chlorali hydras, chloramphenicol, cephalosporins, Cimetidinum, erythromycin, Acidum etacrynicum, ethanol. In case of the combined use of warfarin with above-mentioned drugs it is necessary to carry out control of MHO at the beginning and at the end of treatment and whenever possible in 2–3 weeks from the beginning of therapy.

Contraindications:

Hypersensitivity, acute bleeding, serious illness of a liver or kidneys, heavy arterial hypertension. an acute IDCS, deficit of proteins C is, hemorrhagic diathesis, thrombocytopenia, a peptic ulcer of a stomach and a 12-perstny gut in aggravation stages, hemorrhage in a brain, alcoholism, a renal failure, pregnancy.

Use during pregnancy and feeding by a breast: Pregnant women should not appoint drug in connection with the revealed teratogenic action, development of bleedings in a fruit and death of a fruit. Warfarin is removed with maternal milk in insignificant quantity and practically does not exert impact on coagulability of blood at the child therefore drug can be used in the period of a lactation, however it is desirable to refrain from feeding by a breast in the first 3 days of therapy by warfarin.

Overdose:

Symptoms: bleeding, bleedings. 

Treatment: if the prothrombin time makes more than 5% and there are no other possible bleeding points (нефроуролитиаз, etc.). correction of the mode of dosing is not required. At insignificant bleedings it is necessary to lower a dose of drug or to stop treatment for short term. In case of development of heavy bleeding — vitamin K before recovery of koagulyantny activity. At the menacing bleedings — transfusion of concentrates of factors of a prothrombin complex or freshly frozen plasma, or whole blood.

Storage conditions:

Period of validity 2 years. Not to apply after a period of validity. List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 2,50 mg. On 10 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 3. 5, 10 blister strip packagings on 10 tablets or on 1, 2, 3. 4, 5 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.