Warfarin

Warfarin – anticoagulant of indirect action.

Form of release and structure

Warfarin is produced in the form of tablets, on 5, 10, 14, 20, 25 pieces in blister strip packagings, on 50, 100, 250 pieces in banks.

Active agent – sodium warfarin in number of 2,5 mg is a part of 1 tablet.

Indications to use

Warfarin is appointed for treatment and prevention of thrombosis and an embolism of blood vessels. Indications to use are the following diseases / states:

• Embolism of a pulmonary artery and acute venous thrombosis;
• Repeated embolism of a pulmonary artery;
• Repeated myocardial infarction;
• Postoperative or recurrent venous thrombosis;
• Prosthetics of valves of heart and vessels (it is possible in a combination with acetylsalicylic acid);
• Thrombosis of brain, coronary and peripheral arteries;
• Secondary prevention of a thromboembolism and thrombosis at atrial fibrillation and after a myocardial infarction.

Drug is also used as an additional tool when performing drug or surgical treatment of thrombosis and at electric cardioversion of a ciliary arrhythmia.

Contraindications

Contraindications to use of Warfarin are:

• Pathological changes of blood;
• The diseases and states which are followed by high risk of development of bleedings;
• Recently performed craniocereberal operations;
• Ophthalmologic operations;
• Tendencies to bleeding at digestive tract cankers, diseases of urinogenital and respiratory system;
• Surgical interventions concerning an injury with an extensive surgery field;
• Aneurisms;
• Cerebrovascular hemorrhages;
• Serious illness of kidneys or liver;
• Exudative pericardis, bacterial endocarditis, pericardis;
• Heavy arterial hypertension;
• Acute IDCS;
• The spinal puncture or other diagnostic procedures which are followed by potential threat of developing of uncontrollable bleeding;
• Malignant arterial hypertension;
• Carrying out blockade, extensive regional anesthesia;
• Lack of observation of patients of senile age;
• Inadequate laboratory conditions of observation of the patient;
• Patient's disorganization;
• Psychoses;
• Alcoholism;
• Pregnancy;
• The menacing abortion.

Warfarin in an inactive form is emitted with breast milk. Changes of a prothrombin time are not found in children whose mothers in the period of a lactation accepted drug. Effect of drug at premature newborns was not studied.

Efficiency and safety of Warfarin at children are younger than 18 years are not established.

Route of administration and dosage

Warfarin is accepted inside on 2-10 mg a day. The daily dosage is defined by blood coagulation parameters, reaction of the patient to treatment, a clinical situation.

Side effects

At use of Warfarin development of disturbances from various systems and bodies is possible:

• Alimentary system: cholestasia, nausea, hepatitis, diarrhea, vomiting, increase in activity of liver enzymes, abdominal pains, jaundice;
• Coagulant system of blood: hematomas, bleedings, anemia; seldom – necroses of skin and other fabrics because of local thromboses;
• Central nervous system: headache, lethargy, fatigue, adynamy, taste disturbances, dizziness;
• Cardiovascular system: vasculites, purple coloring of fingers of foot, fever, cryesthesia, paresthesias;
• Respiratory system: seldom – tracheobronchial or tracheal calcification at long therapy (clinical value is not established);
• Allergic reactions: skin itch, hypostasis, skin rash, small tortoiseshell, fever;
• Dermatological reactions: violent rash, dermatitis, alopecia.

Special instructions

The risk of development of bleedings increases at long and intensive anticoagulating care.

During treatment it is necessary to control a dosage and to periodically define a prothrombin time and other parameters of coagulation.

At simultaneous use of Warfarin with other drugs it is necessary to consider high probability of medicinal interaction.

Therapy can increase risk of an embolism particles of atherosclerotic plaques.

Warfarin with extra care and only after the careful analysis of a ratio of advantage and risk should be applied in the following cases:

• Injury which can lead to internal bleeding;
• Infectious diseases (including to a spr) or the dysbacteriosis connected using antibiotics;
• Constant catheters;
• Injury with the extensive bleeding surface or surgical intervention;
• The expected or known deficit of a protein of C;
• Moderate and heavy arterial hypertension;
• Anaphylactic reactions, heavy and moderate allergic reactions;
• Vasculites, Osler's disease, heavy diabetes.

Correction of doses and more frequent laboratory monitoring is necessary for patients with congestive heart failure.

It is not recommended to apply at the same time Warfarin with Streptokinasa and an urokinase.

During therapy special observation is required to patients of advanced age, and also persons with intellectual disturbances.

It is considered that the renal clearance influences intensity of effect of Warfarin slightly.

At abnormal liver functions reduction of metabolism of Warfarin and potentiation of its effects can be observed that is connected with disturbance of synthesis of factors of coagulation.

Medicinal interaction

Simultaneous use of Warfarin with other drugs:

• Anticholinergics – are possible disturbances of attention and memory at patients of advanced age;
• Drugs with antiagregantny activity and anticoagulants – the risk of developing of bleedings increases;
• Hypoglycemic means derivative sulphonylurea – strengthening of their hypoglycemic effect is possible;
• Inhibitors of microsomal enzymes of a liver – the risk of developing of bleeding increases and anticoagulating effect of Warfarin amplifies;
• Cyclosporine – is observed mutual decrease in effects;
• Tiklopidin – is described a case of injury of a liver (effect of Warfarin does not change);
• Acidum etacrynicum – strengthening of a hypopotassemia, diuretic effect is possible;
• Colestyraminum – decreases bioavailability and absorption of Warfarin;
• Phenytoinum – is messages on initial increase in anticoagulating activity with the subsequent its decrease;
• Phenazone – decreases concentration of Warfarin in a blood plasma;
• Enoksatsin – decreases clearance of R-isomer (not S-isomer) at preservation of a prothrombin time;
• Trazodonum, fluoxetine, vitamin E – are available the effects of Warfarin given about strengthening.

Anticoagulating effect of Warfarin is reduced: миансерин, ацитретин, coenzyme Q10, inductors of microsomal enzymes of a liver (including Phenytoinum, barbiturates, carbamazepine), glucagon, rifampicin, paracetamol, глутетимид, griseofulvin, диклоксациллин, retinoids, сукральфат, vitamin K, phenazone, aminoglutethimide, глутетимид, Colestyraminum, diuretics (Spironolactonum and Chlortalidonum), Mitotanum, Mercaptopurinum, ginseng drugs, цизаприд.

Strengthening of anticoagulating effect of Warfarin and increase in risk of developing of bleedings is possible at its simultaneous use with: pyrazyl ketone derivatives (including with Sulfinpyrazonum, phenylbutazone), heparin, non-steroidal anti-inflammatory drugs (including with acetylsalicylic acid), tramadoly, a combination of paracetamol and codeine, dextropropoxyphene, antiarrhytmic means (including with quinidine, Amiodaronum, moratsiziny, propafenony), antifungal and antimicrobic means (including with metronidazole, klaritromitsiny, chloramphenicol, tsefmetazoly, tsefamandoly, erythromycin, tsefoperazony, cefazolin, roksitromitsiny, azithromycin, co-trimoxazole, Miconazolum, ketokonazoly, itrakonazoly, ofloksatsiny, flukonazoly, Acidum nalidixicum, norfloxacin, doxycycline, ciprofloxacin, aminosalicylic acid, tetracyclines, an isoniazid, Neomycinum, benzylpenicillin, aztreonamy), quinine, glibenclamide, valproic acid, cyclophosphamide, proguanil, ftoruratsily, a methotrexate, with combinations of a vindezin and an etopozid or a karboplatin, Tamoxifenum, an ifosfamida with local, flutamidy, simvastatiny, interferon an alpha (at chronic hepatitis C), sakvinaviry, interferon a beta, gemfibrozily, Clofibratum, fenofibraty, danazoly, tsiprofibraty, Cimetidinum, fluvastatiny, lovastatiny, piracetam, tramadoly.

At simultaneous use of Warfarin with tocopherol, Disopyramidum, tricyclic antidepressants, felbamaty, Allopyrinolum, terbinafiny, Chlorali hydras, Dipiridamolum, ascorbic acid, ranitidine data on medicinal interaction are ambiguous.

At the patients with an alcoholism accepting Disulfiramum strengthening of effects of Warfarin is observed.

At accidental reception of a large amount of alcohol strengthening of effect of Warfarin can be also observed.

At regular alcohol intake reduction of effects of drug is possible that can be connected with induction of enzymes of a liver. At injuries of a liver effects of Warfarin can amplify.

Terms and storage conditions

To store in protected from light, the place, dry, unavailable to children, at a temperature up to 25 °C.

Period of validity – 2 years.