Warfarin Nycomed pills 2.5 mg N100
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Active ingredients
Warfarin
Release form
Pills
Composition
1 tablet contains warfarin sodium 2.5 mg excipients: dye indigotin E132, lactose monohydrate, corn starch povidone 30, calcium phosphate, magnesium stearate.
Pharmacological effect
Indirect anticoagulant. Blocks the synthesis of vitamin K-dependent coagulation factors in the liver, namely, II, VII, IX and X. The concentration of these components in the blood decreases, the process of blood coagulation slows down. The beginning of the anticoagulant effect is observed 36-72 hours after the start of the use of the drug with the development of the maximum effect for 5-7 days from the start of the application. After discontinuation of the drug, the recovery of the activity of vitamin K-dependent blood coagulation factors occurs within 4-5 days.
Pharmacokinetics
Absorption and distribution: The drug is rapidly absorbed from the gastrointestinal tract. Binding to plasma proteins is 97-99%. Metabolism: Metabolized in the liver. Warfarin is a racemic mixture, and the R- and S-isomers are metabolized in the liver in various ways. Each of the isomers is converted to 2 major metabolites. The main metabolic catalyst for warfarin S-enantiomer is CYP2C9, and for warfarin R-enantiomer CYP1A2 and CYP3A4. The levorotatory isomer of warfarin (S-warfarin) has 2-5 times more anti-coagulant activity than the degrading isomer (R-enantiomer), however, the latter T1 / 2 is greater. Patients with a CYP2C9 enzyme polymorphism, including CYP2C9 * 2 and CYP2C9 * 3 alleles, may have an increased sensitivity to warfarin and an increased risk of bleeding. Excretion: Warfarin is eliminated from the body in the form of inactive metabolites with bile, which are reabsorbed in the gastrointestinal tract and excreted in the urine. T1 / 2 ranges from 20 to 60 h. For the R-enantiomer, T1 / 2 ranges from 37 to 89 h, and for the S-enantiomer from 21 to 43 h.
Indications
Treatment and prevention of deep vein thrombosis and pulmonary embolism. Secondary prevention of myocardial infarction and prevention of thromboembolic complications (stroke or systemic embolism) after myocardial infarction. Prevention of thromboembolic complications in patients with atrial fibrillation, heart valve damage, or prosthetic heart valves.Prevention of rapid transient ischemic attacks and stroke.
Contraindications
Hypersensitivity to the components of the drug, clinically established bleeding, in order to avoid the risk of severe bleeding within 72 hours after extensive surgical interventions, within 48 hours in the postpartum period, the tendency to bleeding (hemophilia, von Willebrand disease, thrombocytopenia and dysfunction of platelets) fall. severe renal failure, severe liver failure, cirrhosis, untreated or uncontrolled arterial hypertension. recent hemorrhagic stroke, a state of health that causes intracranial hemorrhage, such as cerebral artery aneurysm, aortic aneurysm, central nervous system operations or eye operations, gastrointestinal or renal hemorrhages and their complications, diverticulosis or malignant tumors, esophageal varices, pericarditis (including exudative). A condition in which therapy cannot be administered safely enough (for example, psychosis, dementia, alcoholism).
Precautionary measures
From the side of the blood system: very often - bleeding (in various organs); often - hypersensitivity to warfarin after prolonged use. On the part of the digestive system: often - vomiting, nausea, diarrhea; very rarely - melena. On the part of the skin and subcutaneous tissues: rarely - vasculitis, skin necrosis, alopecia, rash, urticaria, itching. Since the cardiovascular system: rarely - violet finger syndrome; very rarely - cholesterol embolism. On the part of the immune system: often - hypersensitivity. On the part of the liver: rarely - increased activity of liver enzymes, jaundice.
Use during pregnancy and lactation
Warfarin quickly penetrates the placental barrier, has a teratogenic effect on the fetus, leading to the development of warfarin syndrome in the fetus at 6-12 weeks of pregnancy. Manifestations of this syndrome: nasal hypoplasia (saddle nose deformity and other changes in cartilage) and punctate chondrodysplasia during X-ray (especially in the spine and long tubular bones), short hands and fingers, atrophy of the optic nerve, cataract leading to complete blindness, mental retardation and physical development, microcephaly. The drug may cause bleeding at the end of pregnancy and during labor. Taking the drug during pregnancy can cause congenital malformations and lead to death of the fetus.The drug should not be prescribed in the first trimester of pregnancy and in the last 4 weeks. The use of warfarin is not recommended in the remaining periods of pregnancy, except in cases of extreme necessity. Women of reproductive age should use an effective method of contraception during the period of warfarin use. Warfarin is excreted in breast milk, but when taking warfarin in therapeutic doses, no effect on the fed child is expected. The drug can be used during lactation (breastfeeding). Data on the effect of warfarin on fertility are not available.
Dosage and administration
Target level of INR (International Normalizing Index) for oral anticoagulant therapy. Prevention of thromboembolic complications in patients with prosthetic heart valves: INR 2.5-3.5. Other indications: PIM 2.0-3.0. Adult patients with normal weight and spontaneous PIM below 1.2 are prescribed 10 mg of warfarin for three consecutive days. Then the dose is calculated in accordance with the table below, based on the measurement of the PIM on the fourth day. "In open care" and in patients with hereditary protein C or S deficiency, the recommended dose is 5 mg of warfarin for three consecutive days. Then the dose is calculated in accordance with the table below, based on the measurement of the PIM on the fourth day. For elderly patients, patients with low body mass, with spontaneous MSI above 1.2, or those who have comorbidities or receive any medications that affect the effectiveness of anticoagulant therapy, the recommended dose is 5 mg of warfarin over the next two days. Then the dose is calculated in accordance with the table below, based on the measurement of PIM on the third day. PIM measurements are performed daily until a stable target level is reached, which is usually set on the 5-6th day of treatment. PWR measurements are then carried out weekly, reaching a 4-week interval. In the case of large deviations in the level of MNI or in patients with liver diseases or diseases, the absorption of vitamin K is affected, the measurement intervals may be less than 4 weeks. Appointment of new or cancellation of drugs, previously taken, requires additional measurements MNI. With long-term therapy, adjustments are made to a weekly dose of warfarin in accordance with the table above.If the dose requires correction, then the next measurement of the INR should be carried out 1 or 2 weeks after the correction. After this, measurements continue until a 4-week interval is reached. Children: anticoagulant therapy in children is carried out under the supervision of pediatricians. Doses are selected in accordance with the table below. Scheduled operations: pre-, re-and postoperative anticoagulant therapy is carried out as indicated below. Determine the PIM a week before the scheduled operation. Stop taking warfarin 1-5 days before surgery. In case of a high risk of thrombosis, low molecular weight heparin is injected subcutaneously to the patient for prophylaxis. The duration of the pause in the reception of warfarin depends on the PIM. Reception of warfarin is stopped for 5 days before the operation, if the INR is> 4.0; 3 days before the operation, if the PID = from 3.0 to 4.0; 2 days before the operation, if PIM = 2.0 to 3.0. Determine the PWI in the evening before the operation and inject 0.5-1.0 mg of vitamin K 1 orally or intravenously if the PWI is> 1.8. Take into account the need for infusion of unfractionated heparin or prophylactic administration of low molecular weight heparin on the day of surgery. Continue subcutaneous administration of low molecular weight heparin for 5–7 days after surgery with concomitant, restored warfarin. Continue taking warfarin with a regular maintenance dose on the same day in the evening after small operations and on the day when the patient begins to receive enteral nutrition after major operations.
Side effects
Frequent manifestations of side effects of warfarin are bleeding and bleeding that can occur from any organ (for example, bleeding from the nose, hemoptysis, hematuria, bleeding gums, bruising, vaginal bleeding, bleeding into the conjunctiva of the eye, gastrointestinal bleeding, prolonged and abundant bleeding, vaginal bleeding, bleeding in the conjunctiva of the eye, gastrointestinal bleeding, prolonged and heavy bleeding surgical interventions and after injuries). Hemorrhages can be serious and lead to death, hospitalization, transfusions to patients who have been treated with long-term anticoagulants. The following factors influence the development of bleeding with warfarin: advanced age, high intensity of concomitant anti-coagulant therapy, the history of stroke, and the number of cases in the history of stroke, which is inherently instilled, and there is one case that is in place in the history of instillation. ,atrial arrhythmias, as well as patients with CYP2C9 gene polymorphism. The level of hemoglobin and MNI should be carefully monitored. The side effects are classified according to their incidence rate into such categories. Very often (> 1/10), often (> 1/100 and less than 1/10), rarely ( > 1/1000 less than 1/100), rarely (> 1/1000 and less than 1/1000), very rarely (less than 1/10000). Sideways blood and lymphatic system. Very frequent bleeding. Frequently hypersensitivity to warfarin after long-term treatment. Often anemia. Rarely eosinophilia. On the part of the digestive tract. Often a, abdominal pain, nausea, diarrhea. From the side of the digestive system. Rarely elevated liver enzymes, jaundice. On the skin and subcutaneous tissues. Rarely eczema, vasculitis, skin necrosis, alopecia, rash, urticaria, pruritus. Rarely, nephritis, urolithiasis, and tubular necrosis. In the post-marketing period, as a result of the use of warfarin, the following adverse reactions decreased hematocrit. Fever, tracheal calcification. cholestatic hepatitis, pancreatitis priapizm. allergic reactions. purpura. Cranial cerebral bleeding, subdural hematoma. hemothorax, bleeding from erect, vomiting blood, melena. A frequent risk factor for the occurrence of intracranial hemorrhage is untreated or uncontrolled hypertension. The probability of bleeding increases if MNI significantly higher than the target level. If the bleeding started, PREMNY, which is within the target level, this means the existence of other related conditions that must be investigated. The purple finger syndrome is a rare complication of receptionarfarin. This is typical of male patients with saterosclerotic diseases. It is believed that warfarin causes hemorrhagic athematoid plaques that lead to microembolism. Symmetrical purple lesions of the skin of the fingers and the lower surface of the foot occur, and such lesions are accompanied by burning pain. Acceptance of paraffarfarin should be stopped, and skin lesions usually gradually disappear. Erythematous edema of the skin, leading to ecchymomas, heart attack and necrosis of the skin. Necrosis usually begins with swelling of the skin of the limbs or buttocks, darkened, but may appear in other places. Later, these lesions become necrotic.90% of patients with such lesions are women. Lesions are observed from the 3rd to the 10th day of administration and the etiology implies the insufficiency of the antithrombotic protein C or B. Congenital insufficiency of these proteins can be the cause of complications. For this reason, warfarin intake should begin in small initial doses, simultaneously with the introduction of heparin. If a complication occurs, the tolerance of warfarin is stopped and the administration of heparin is continued to heal or scar the lesions.
Overdose
Symptoms: The cure rate is at the borderline of bleeding, so the patient may have minor bleeding (including microhematuria, bleeding gums). Treatment: in mild cases, it is enough to reduce the dose of the drug or stop treatment for a short time. With minor bleeding enough to stop taking the drug to achieve the target level MHO. In the case of severe bleeding, it is recommended in / in the introduction of vitamin K, the coagulation factor concentrate or fresh frozen plasma, the ingestion of activated carbon inside. If oral anticoagulants are indicated for further administration, large doses of vitamin K should be avoided, since warfarin resistance develops within 2 weeks.
Interaction with other drugs
It is not recommended to start or stop taking other medicines, to change the dose of drugs taken without consulting with your doctor. With simultaneous appointment, it is also necessary to take into account the effects of stopping the induction and / or inhibition of the effect of warfarin by other drugs. The risk of severe bleeding increases with simultaneous use of warfarin with drugs that affect platelet levels and primary hemostasis: acetylsalicylic acid, clopidogrel, ticlopidine, dipyridamole, most NSAIDs (except for COX-2 inhibitors), penicillin antibiotics in large doses. You should also avoid the combined use of warfarin with drugs that have a pronounced inhibitory effect on the isoenzymes of the cytochrome P450 system (for example, cimetidine, chloramphenicol), which, if taken, increases the risk of bleeding for several days. In such cases, cimetidine can be replaced, for example, with ranitidine or famotidine.Medications that reduce the effect of warfarin Kolestiramine: a decrease in the absorption of warfarin and the effect on enterohepatic recirculation. Bosentan: induction of conversion of warfarin to CYP2C9 / CYP3A4 in the liver. Aprepitant: induction of conversion of warfarin to CYP2C9. Mesalazine: a reduction in the anticoagulant effect of warfarin is possible. Sukollfat: the probability of reducing the absorption of warfarin. Griseofulvin: reduction of the coumarin anticoagulant effect. Retinoids: the possibility of reducing the activity of warfarin. Dicloxacillin: increased metabolism of warfarin. Rifampicin: increased metabolism of warfarin; It is necessary to avoid joint use of these drugs. Antivirals (nevirapine, ritonavir): increased metabolism of warfarin mediated by CYP2C9. Nafcillin: reduced anticoagulant effect of warfarin. Phenazone: induction of enzyme metabolism, reduction in the concentration of warfarin in the blood plasma; may require an increase in the dose of warfarin. Rofecoxib: The mechanism of interaction is unknown. Barbiturates (for example, phenobarbital): increased metabolism of warfarin. Antiepileptic drugs (carbamazepine, valproic acid, primidone): increased metabolism of warfarin. Antidepressants (trazodone, mianserin): in four cases of clinical use, it was found that the interaction of trazodone and warfarin caused a decrease in prothrombin time and INR, but the mechanism of this interaction is unknown. The mechanism of interaction between warfarin and mianserin is also unknown. Glutetemide: a decrease in the anticoagulant effect of warfarin due to an increase in its metabolism. Chlordiazepoxide: a decrease in the anticoagulant effect of warfarin. Aminoglutethimide: increased metabolism of warfarin. Azathioprine: a decrease in the absorption of warfarin and an increase in the metabolism of warfarin. Mercaptopurin: Reduction of the anticoagulant effect of warfarin. Mitotan: a reduction in the anticoagulant effect of warfarin is possible. Cyclosporin: warfarin increases the concentration of cyclosporine or enhances its effect, affecting the metabolism of cyclosporine. Kolestiramine: may reduce the anticoagulant effect of warfarin due to a decrease in its absorption. Spironolactone, chlorthalidone: the use of diuretics in the case of a pronounced hypovolemic action can lead to an increase in the concentration of clotting factors, which reduces the effect of anticoagulants.Hypericum perforatum (Hypericum perforatum): increases the metabolism of warfarin by CYP3A4 and CYP1A2 (metabolism of R-warfarin), as well as by CYP2C9 (metabolism of S-warfarin); the effect of enzyme induction may persist for 2 weeks after the end of the application of Hypericum perforatum. In the event that the patient is taking drugs of Hypericum perforatum, measure INR and stop taking it. It should be carefully monitored by the INR, since its level may increase with the abolition of the Hypericum perforatum; after that you can assign warfarin. Ginseng (Panax ginseng): induction of warfarin conversion in the liver is possible; It is necessary to avoid joint use of these drugs. Foods containing vitamin K: weaken the effect of warfarin. Most of all vitamin K is found in green vegetables (for example, amaranth greens, avocados, broccoli, Brussels sprouts, cabbage, canola oil, shayo leaf, onion, coriander (cilantro), borage, chicory, kiwi fruit, lettuce, mint , mustard greens, olive oil, parsley, peas, pistachios, red seaweed, spinach greens, spring onions, soybeans, tea leaves (but not tea-drink), turnip greens, watercress), therefore, when treating warfarin, be careful to eat these products. Vitamin C: reduction of the anticoagulant effect of warfarin. Vitamin K: Warfarin blocks the synthesis of vitamin K-dependent coagulation factors. Agents that enhance the effect of warfarin Abciximab, tirofiban, eptifibatid, clopidogrel, heparin: an additional effect on the hematopoietic system. Cimetidine: a pronounced inhibitory effect on the cytochrome P450 system (cimetidine can be replaced by ranitidine or famotidine), leading to a decrease in the metabolism of warfarin. Glibenclamide: increased anticoagulant effect of warfarin. Omerpazole: increased anti-coagulant effect of warfarin. Amiodarone: reduced metabolism of warfarin after one week of combined use; This effect may persist for 1-3 months after the cancellation of amiodarone. Ethacrynic acid: may enhance the effect of warfarin due to the displacement of warfarin from bonds with proteins. Lipid-lowering drugs (fluvastatin, simvastatin, rosuvastatin, gemfibrozil, bezafibrat, clofibrate, lovastatin, fenofibrate): competition for metabolism mediated by CYP2C9 and CYP3A4. Propafenone: reduced metabolism of warfarin. Quinidine: reduced synthesis of coagulation factors.Diazoxide: can substitute for warfarin, bilirubin or another substance that is highly bound to a protein from protein bonds. Digoxin: increased anticoagulant effect. Propranolol: increased anticoagulant effect. Ticlopidine: increased risk of bleeding; monitoring of INR is required. Dipyridamole: increased concentration of warfarin or dipyridamole due to potentiation of effects; increased risk of bleeding (hemorrhage). Miconazole (including in the form of a gel for the oral cavity): a decrease in the own clearance of warfarin and an increase in the free fraction of warfarin in the blood plasma; decrease in the metabolism of warfarin mediated by enzymes of the cytochrome P450 system. Steroid hormones - anabolic and / or androgens (danazol, testosterone): reduction of warfarin metabolism and / or direct effect on the coagulation and fibrinolysis systems. Drugs acting on the thyroid gland: increased metabolism of vitamin K-dependent coagulation factors. Glucagon: increased anticoagulant effect of warfarin. Allopurinol: increased anticoagulant effect of warfarin. Sulfinpyrazon: increased anticoagulant effect due to a decrease in its metabolism and weakening of the connection with proteins. High-dose penicillins (cloxacillin, amoxicillin): you may increase the likelihood of bleeding, including bleeding from the gums, nose, the appearance of unusual bruising or dark stools. Tetracyclines: may increase the anticoagulant effect of warfarin. Sulfonamides (sulfamethizol, sulfafurazole, sulfafenazol): the anticoagulant effect of warfarin may be enhanced. Quinolones (ciprofloxacin, norfloxacin, ofloxacin, grepafloxacin, nalidixic acid): decreased metabolism of warfarin. Macrolide antibiotics (azithromycin, clarithromycin, erythromycin, roxithromycin): reduced warfarin metabolism. Antifungal agents (fluconazole, itraconazole, ketoconazole): reduced metabolism of warfarin. Chloramphenicol: reduced metabolism of warfarin, a pronounced inhibitory effect on the cytochrome P450 system. Cephalosporins (cefamundol, cefalexin, cefmenoxime, cefmetazole, cefoperazone, cefuroxime): increased effect of warfarin due to the suppression of the synthesis of vitamin K-dependent blood clotting factors and other mechanisms.Sulfamethoxazole / trimethoprim: a decrease in the metabolism of warfarin and the displacement of warfarin from the sites of binding to plasma proteins. Levamisole: increased anti-coagulant effect of warfarin. Codeine: A combination of codeine and paracetamol enhances the activity of warfarin. Acetylsalicylic acid: displacement of warfarin from albumin binding sites, restriction of warfarin metabolism. NSAIDs (azapropazone, indomethacin, oxyfenbutazone, piroxicam, sulindac, tolmetin, feprazon, celecoxib, and others (except for COX-2 inhibitors): competition for metabolism carried out by CYP2C9. Leflunomide: restriction of metabolism of warfarin, mediated by CYPCC. after 1-2 weeks of continuous use: restriction of metabolism of warfarin or the effect on the formation of coagulation factors (this effect does not appear when paracetamol is used in a dose of less than 2 g / day). Phenylbutazone: decrease in the metabolism of warfari a, displacement of warfarin from plasma protein binding sites; use of this combination should be avoided. Narcotic analgesics (dextropropoxyphene): increased anticoagulant effect of warfarin. : competition for metabolism mediated by CYP3A4. Antidepressants are selective serotonin reuptake inhibitors (SSRIs), incl. fluoxetine, fluvoxamine, paroxetine, sertraline: restriction of warfarin metabolism. It is believed that SSRIs limit the CYP2C9 isoenzyme. This enzyme metabolizes the most potent isomer, S-warfarin. In addition, both SSRIs and warfarin bind strongly to albumin, as a result of which the possibility of displacing one of them from protein-binding sites increases (when used simultaneously). Chloral hydrate: interaction mechanism unknown. Fluorouracil: decreased synthesis of CYP2C9, which metabolizes warfarin. Capecitabine: Reduced CYP2C9 synthesis. Imatinib: competitive suppression of CYP3A4 isoenzyme and suppression of warfarin metabolism mediated by CYP2C9 and CYP2D6. Ifosfamide: Suppression of CYP3A4. Tamoxifen: an inhibitor of CYP2C9, may increase the concentration of warfarin in serum due to a decrease in its metabolism.Methotrexate: increased effect of warfarin due to reduced synthesis of procoagulant factors in the liver. Tegafur: increased anti-coagulant effect of warfarin. Trastuzumab: increased anti-coagulant effect of warfarin. Flutamide: increased anti-coagulant effect of warfarin. Cyclophosphamide: the probability of a change in the anticoagulant effect of warfarin, because cyclophosphamide is an antitumor agent. Etoposide: may enhance the anticoagulant effect of coumarins. Interferon alpha and beta: an increase in the anticoagulant effect and an increase in the serum concentration of warfarin makes it necessary to reduce the dose of warfarin. Disulfiram: decreased metabolism of warfarin. Metolazon: increased anti-coagulant effect of warfarin. Thienyl Acid: Enhanced Anti-Coagulant Effect of Warfarin Zafirlukast: increasing the concentration or enhancing the effect of zafirlukast on the background of the use of warfarin due to changes in the metabolism of zafirlukast. Troglitazone: a decrease in the concentration or weakening of the effect of warfarin due to changes in the metabolism of warfarin. Influenza vaccine: the possibility of enhancing the anticoagulant effect of warfarin. Proguanil: may enhance the anticoagulant effect of warfarin according to individual reports. Food (cranberry): reduces the metabolism of warfarin, mediated by CYP2C9. Quinine-containing tonic beverages: consuming large amounts of quinine-containing tonic beverages may result in the need to reduce the dose of warfarin. This interaction can be explained by the fact that quinine reduces the synthesis of procoagulant factors in the liver. Ginkgo (Ginkgo biloba), garlic (Allium sativum), medicinal (Angelica sinensis), papaya (Carica papaya), sage (Salvia miltiorrhiza): potentiation of the anticoagulant / anti-platelet effect may increase the risk of bleeding. Medications that reduce or enhance the effect of warfarin: Disopyramide: may weaken or strengthen the anticoagulant effect of warfarin. Coenzyme-Q10: may enhance or suppress the effect of warfarin due to the homogeneity of the chemical structure with vitamin K. Ethanol: inhibition or induction of warfarin metabolism. Warfarin may enhance the effect of oral hypoglycemic agents (sulfonylurea derivatives).In the case of combined use of warfarin with the above drugs, it is necessary to monitor the INR at the beginning and at the end of treatment and, if possible, 2-3 weeks after the start of therapy.
special instructions
A prerequisite for warfarin therapy is strict patient compliance with the prescribed dose of the drug. Patients suffering from alcoholism, as well as patients with dementia, may be unable to comply with the prescribed regimen of warfarin. Fever, hyperthyroidism, decompensated heart failure, alcoholism with concomitant liver damage, may enhance the effect of warfarin. In hypothyroidism, the effect of warfarin can be reduced. In the case of renal failure or nephrotic syndrome, the level of the free fraction of warfarin in the blood plasma increases, which, depending on the associated diseases, can lead to both an increase and a decrease in the effect. In the case of moderate liver failure, the effect of warfarin is enhanced. In all of the above conditions, careful monitoring of the MHO should be carried out. Patients receiving warfarin are recommended to prescribe paracetamol, tramadol or opiates as painkillers. Patients with a mutation of the gene encoding the CYP2C9 enzyme have a longer T1 / 2 warfarin. These patients require lower doses of the drug, since the risk of bleeding increases when taking the usual therapeutic doses. Warfarin should not be taken in patients with rare hereditary intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome due to the presence of lactose in the preparation (as an auxiliary substance). If necessary, the onset of a rapid antithrombotic effect, it is recommended to begin treatment with the introduction of heparin; then, within 5-7 days, combination therapy with heparin and warfarin should be carried out until the target value of MHO is maintained for 2 days. In patients with protein C deficiency, there is a risk of skin necrosis without the use of a shock dose of warfarin. This therapy should be started without the use of a shock dose of warfarin, even with heparin.Patients with protein deficiency S may also be at risk; in these circumstances, a slower initiation of warfarin therapy is recommended. In the case of individual resistance to warfarin (rarely found), from 5 to 20 shock doses of warfarin are needed to achieve a therapeutic effect. If taking warfarin in these patients is ineffective, other possible causes should be established: simultaneous use of warfarin with other drugs, inadequate diet, laboratory errors. The treatment of elderly patients should be carried out with special precautions, since the synthesis of coagulation factors and hepatic metabolism in these patients is reduced, as a result of which there may be an excessive effect from the action of warfarin. It is recommended to be careful in patients with impaired renal function, as a result of which the level of INR in patients at risk of hypercoagulation, for example, in severe hypertension or kidney disease should be monitored more often.