Warfarin - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate dihydrate 65.5 mg, microcrystalline cellulose 60 mg, silicon dioxide colloid 1 mg, copovidone 6 mg, croscarmellose sodium 4 mg, magnesium stearate 1 mg.

Description:

Tablets are white or white with a yellowish hue, biconvex with a cruciform risk.

Pharmacotherapeutic group:Anticoagulant means of indirect action

ATX: & nbsp

B.01.A.A.03 Warfarin

B.01.A.A Antagonists of vitamin K

Pharmacodynamics:Anticoagulant of indirect action. Suppresses the synthesis of vitamin K-dependent factors of blood coagulation (II, VII, IX and X) in the liver and proteins C and S in the liver. The optimal anticoagulant effect is observed on 3-5 days from the beginning of application and stops 3-5 days after the last dose.

Pharmacokinetics:

After oral administration warfarin completely absorbed in the gastrointestinal tract (GIT). Connection with blood plasma proteins - 97-99%. The therapeutic concentration in plasma is -1-5 μg / ml (0.003-0.015 mmol / l). It is in the form of a racemic compound, while in the human body the L-isomer has more activity than the dextrorotatory. Penetrates through the placenta, but is not secreted with breast milk.

The drug is metabolized in the liver with the formation of inactive and weakly active metabolites, which are reabsorbed from the bile, while the L-isomer is metabolized faster. The half-life of racemic warfarin is 40 hours. It is excreted by the kidneys.

Indications:Treatment and prevention of thrombosis and thromboembolism of vessels: acute venous thrombosis and pulmonary embolism; postoperative thrombosis; repeated myocardial infarction; as an additional drug (LS) in the conduct of surgical or thrombolytic treatment of thrombosis, as well as electrical cardioversion of atrial fibrillation; recurrent venous thrombosis; recurrent thromboembolism of the pulmonary arteries; prosthetics of valvular and vascular valves (combination with acetylsalicylic acid (ASA) is possible, thrombosis of peripheral,coronary and cerebral arteries; secondary prevention of thrombosis and thromboembolism after myocardial infarction and atrial fibrillation.

Contraindications:Hypersensitivity, acute bleeding, severe liver or kidney disease, severe arterial hypertension, acute DIC syndrome, deficiency of proteins C and S, hemorrhagic diathesis, thrombocytopenia, peptic ulcer and duodenal ulcer in the acute stage, cerebral hemorrhage, alcoholism, kidney failure, pregnancy.

Pregnancy and lactation:The drug should not be given to pregnant women due to an identified teratogenic effect, the development of bleeding in the fetus and the death of the fetus. Warfarin is excreted with maternal milk in small amounts and has almost no effect on blood clotting in a child, so the drug can be used during lactation, but it is advisable to refrain from breastfeeding during the first 3 days of therapy with warfarin.

Dosing and Administration:Inside, in one go, at the same time of day. The initial dose of -2.5-5 mg / day. Further dosing regimens are set individually, depending on the results of the prothrombin time or the International Normalized Ratio (MHO).Prothrombin time should be increased 2-4 times from the initial, and MHO should reach 2.2-4.4 depending on the disease, the risk of thrombosis, the risk of bleeding and individual characteristics of the patient.

When determining the MHO should take into account the sensitivity index of thromboplastin and use this indicator as a correction factor (1.22 - using the domestic thromboplastin from the brain of a rabbit "Neoplast" and 1,2 - using a thromboplastin firm "Roche Diagnostics"). Older and weakened patients are usually prescribed lower doses of the drug.

Before the forthcoming surgical intervention (at a high risk of thromboembolic complications) treatment is started 2-3 days before the operation.

In the case of acute thrombosis treatment is carried out in combination with heparin until the effect of oral anticoagulant therapy is fully manifested (not earlier than 3-5 days of treatment). When prosthetic heart valves, acute venous thrombosis of veins or thromboembolism (at the initial stages), thrombosis of the left ventricle and for the prevention of myocardial ischemia, one should strive for an effective action, which is noted at MHO - 2,8-4,0.In the case of atrial fibrillation and with maintenance therapy for thrombosis, veins and thromboembolism are treated with a moderate anticoagulant effect (MHO 2-3). When the combined use of warfarin with ASA, the MHO should be between 2-2.5. The duration of treatment depends on the patient's condition. Treatment can be canceled immediately.

Side effects:Most often - bleeding. Rarely - diarrhea, increased activity of "liver" transaminases, eczema, skin necrosis; vasculitis, hair loss.

Overdose:Symptoms: bleeding, bleeding. Treatment: in the event that the prothrombin time is more than 5% and there are no other possible sources of bleeding (nephrourolythiasis, etc.), correction of the dosing regimen is not required. With minor bleeding, it is necessary to reduce the dose of the drug or discontinue treatment for a short time. In case of severe bleeding - vitamin K before the recovery of coagulant activity. In case of threatening bleeding, transfusion of the concentrates of factors of the prothrombin complex or fresh frozen plasma or whole blood.

Interaction:

Non-steroidal anti-inflammatory drugs (NSAIDs), dipyridamole, valproic acid, inhibitors of cytochrome P450 (cimetidine, chloramphenicol) increase the risk of bleeding. Combined use of these drugs and warfarin should be avoided (cimetidine can be replaced by ranitidine or famotidine). If it is necessary to treat chloramphenicol, anticoagulant therapy should be temporarily discontinued. Diuretics can reduce the effect of anticoagulants (in the case of pronounced hypobolemic effects, which may lead to an increase in the concentration of clotting factors).

Weaken the action: barbiturates, vitamin K, glutetimide, griseofulvin, dicloxacillin, carbamazepine, mianserin, paracetamol, retinoids, rifampiCin, sucralfate, phenazone, kostyramamine.

Strengthen: allopurinol, amiodarone, anabolic steroids (alkylated at the C17 position), ASA and other NSAIDs, heparin, glibenclamide, glucagon, danazol, diazoxide, disopyramide, disulfiram, isoniazid, ketoconazole, clarithromycin, clofibrate, levamisole, metronidazole, miconazole, nalidixic acid, nilutamide, omeprazole, paroxetine, proguanil, peroral hypoglycemic drugs - derivatives of sulfonamides, simvastatin, sulfonamides, tamoxifen, thyroxine, quinine, quinidine, fluvoxamine, fluconazole, fluorouracil, quinolones, chloral hydrate, chloramphenicol, cephalosporins, cimetidine, erythromycin, ethacrynic acid, ethanol. In the case of combined use of warfarin with the above drugs, it is necessary to carry out MHO monitoring at the beginning and at the end of treatment and, if possible, 2-3 weeks after the start of therapy.

When using drugs (for example, laxative drugs), which may increase the risk of bleeding due to a decrease in normal coagulation (inhibition of clotting factors or liver enzymes), the strategy of anticoagulant therapy should be determined by the possibility of conducting laboratory monitoring. If frequent laboratory monitoring is possible, if the need for therapy with such drugs, the dose of warfarin can be reduced by 5-10%. If the laboratory control is difficult, then, if necessary, the appointment of these drugs warfarin should be canceled.

Special instructions:Before the start of therapy, determine the MHO index (resp. Prothrombin time, taking into account the thromboplastin sensitivity factor). In the future, a regular (every 2-4-8 weeks) laboratory monitoring is carried out.During the period of treatment should refrain from the use of ethanol (risk of hypoprothrombinemia and bleeding).

Form release / dosage:Tablets of 2.50 mg.

Packaging:For 10, 20 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. 3, 5, 10 contour cell packs of 10 tablets or contour of cellular packages 5 to 20 tablets, 1, 2, 3, 4, 5 contour cell packs of 30 tablets together with instructions for use placed in a pile of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006276/09

Date of registration:10.08.2009 / 14.06.2013

Expiration Date:Unlimited

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp23.01.2017

Illustrated instructions

Instructions

Warfarin (Warfarin)