Warfarin (or 4-hydroxycoumarin) – anticoagulant which prevents the vitamin K-dependent blood clotting factor synthesis. Of the existing isomers potency warfarin andriol tc S-isomer in about 5 times higher than R-isomer of warfarin.
The pharmacological effect of warfarin is based on ability to prevent the action of vitamin K in synthesis of clotting factors II, VII, IX and X. In therapeutic warfarin doses reduces the rate of synthesis of clotting factors by 30 – 50%, and decreases their biological activity. The full effect is 2 – 7 day (in the already circulating in the blood clotting factors during this time removed from the body).
Following oral administration of warfarin bioavailability of> 90%, the maximum concentration achieved within 3-9 hours in plasma. Simultaneous food intake delays absorption, but it does not reduce the absorption quantitatively. There is some enterohepatic recycling. Warfarin is almost completely bound to serum albumin-free fraction content varies from 0.5 to 3%. The volume of distribution is approximately 0.14 l / kg. Warfarin crosses the placenta but not excreted in breast milk.Warfarin is metabolized in the liver. By catalysis CYP2C9 (S-isomer) and CYP1A2 and CYP1A3 (R-isomer) of warfarin becomes inactive metabolites that are excreted in urine. Half-life of S-isomer is 18-35 hours warfarin, R-isomer warfarin – 20-70 hours.
– Treatment and prevention of deep vein thrombosis and pulmonary embolism.
– Secondary prevention of myocardial infarction and prevention of thromboembolic complications after myocardial infarction.
– Prophylaxis of thromboembolic complications in patients with atrial fibrillation, lesions of the heart valves or prosthetic heart valves.
– Treatment and Prevention transient ischemic attacks and strokes.
– Pregnancy I and III trimesters.
– Bleeding tendency (von Willebrand disease, hemophilia, thrombocytopenia, platelet dysfunction, hemorrhagic diathesis).
– Severe liver or kidney failure, severe liver or kidney disease; obstructive jaundice.
– Infective endocarditis or pericardial effusion.
– Hypersensitivity and / or individual intolerance of components.
– Acute DIC.
– Conditions that predispose to gastrointestinal bleeding or renal (such as the previously observed with gastrointestinal complications intestinal bleeding, peptic ulcer and duodenal ulcer in the acute stage, diverticulosis, malignant tumor).
– Severe hypertension.
– A recent intracranial hemorrhage, such as an aneurysm of cerebral arteries. Tendency to fall.
– Newly transferred or implied complicated operations on the central nervous system, ophthalmic surgery and diagnostic procedures.
– Dementia, psychoses, alcoholism, and other andriol tc conditions where marked lack of opportunity to assess the state of the blood coagulation system by laboratory methods.
Pregnancy and lactation.
Marevan crosses the placenta, has teratogenic effects (nasal hypoplasia and chondrodysplasia) 6 – 12 weeks of pregnancy. The drug can cause bleeding in the fetus in late pregnancy and during labor.Marevan is absolutely contraindicated in I and III trimester of pregnancy. The remaining phases of pregnancy, use of the drug for anticoagulant therapy should be carried out with careful assessment of the likely benefits the mother and fetus on purpose / fails to appoint the drug.
The drug is not excreted in breast milk and can be used during lactation, however, advisable to abstain from breast-feeding in the first 3 days of therapy Marevanom.
Dosage and administration. Adults: Patients with normal weight and spontaneous international normalized ratio (MHO) of less than 1.2 mg of warfarin is prescribed to 10.5 for three consecutive days. Then, the dose is calculated in accordance with the table below, based on the measurement of MHO on the fourth day of therapy.
In the outpatient setting and in patients with hereditary protein C or S deficiency recommended initial dose is 4.5 mg of warfarin for three consecutive days. Then, the dose is calculated in accordance with the table below, based on the measurement of MHO on the fourth day of therapy.
For older patients, patients with low body weight, with a spontaneous MHO more than 1.2 or with co-morbidities (see. Section “Special Instructions”), or receiving any medicines that affect the effectiveness of anticoagulant therapy, the recommended initial dose of warfarin is 4.5 mg for two consecutive days. Then, the dose is calculated in accordance with the table below, based on the MHO measured on the andriol tc third day of treatment.