Warfarin 5 mg tablet number 30

Warfarin (WARFARIN ORION) user manual

Composition

active ingredient: 1 tablet contains 3 mg of sodium warfarin or 5 mg;
excipients: lactose, corn starch, gelatin, magnesium stearate, indigo E 132 (3 mg tablets) or erythrosine E 127 (5 mg tablets).

Dosage form

Pills.

Pharmacological group

Antithrombotic agents. Antagonists of vitamin K. The code of ATS B01A A03.

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.Prophylaxis of thromboembolic complications in patients with atrial fibrillation, lesions of the heart valves or prosthetic heart valves. Prophylaxis of rapidly transient ischemic attacks and stroke.

Contraindications

Hypersensitivity to warfarin or any of the excipients, acute bleeding, tendency to bleeding (Willebrand disease, hemophilia, thrombocytopenia and impaired platelet function), to avoid the risk of severe bleeding within 72 hours after extensive surgery, for 48 hours in the postpartum period, severe renal failure, severe hepatic insufficiency and cirrhosis, untreated or uncontrolled hypertension, recent intracranial hemorrhage e, a health condition that results in intracranial hemorrhage, for example aneurysm of the cerebral arteries, aortic aneurysm, a tendency to fall, lumbar puncture, central nervous system or eye surgery, gastrointestinal or renal bleeding and their complications, diverticulosis or malignant tumors, varicose veins esophageal veins, infective endocarditis or exudative pericarditis, dementia, psychosis, alcoholism and other situations where compliance may be insufficient and anticoagulant therapy can not conducted safely enough.

Dosing and Administration

The target level of PI (International Normalizing Index) for oral anticoagulant therapy:

Prevention of thromboembolic complications in patients with prosthetic heart valves: MNI 2.5-3.5.

Other indications: MNI 2.0-3.0.

Adults in patients with normal weight and spontaneous MNI below 1.2 are prescribed 10 mg of warfarin for three consecutive days. The dose is then calculated according to the table below, based on the measurement of PIM on the fourth day.

"In open care" and in patients with hereditary deficiency of protein C or S, the recommended dose is 5 mg of warfarin for three consecutive days. The dose is then calculated according to the table below, based on the measurement of PIM on the fourth day.

For elderly patients, patients with a small body weight, with spontaneous MSR greater than 1.2, or those who have co-morbidities or receive any medications that affect the effectiveness of anticoagulant therapy, the recommended dose is 5 mg of warfarin for the next two days. The dose is then calculated according to the table below, based on the measurement of PIM on the third day.

Day	IHP	Dose of warfarin, mg / day
1	-	10 (5 *)
2	-	10 (5 *)
3	<2 from 2 to 2.4 from 2.5 to 2.9 from 3 to 3,4 from 3,5 to 4 > 4	10 (5 *) 5 3 2.5 1.5 Skip one day
4-6	<1.4 from 1.4 to 1.9 from 2 to 2.4 from 2.5 to 2.9 from 3 to 3.9 from 4 to 4,5 > 4.5	10 7.5 5 4,5 3 Skip one day, then 1.5 Skip two days, then 1.5
7th	1.1 to 1.4 from 1.5 to 1.9 from 2 to 3 from 3,1 to 4,5 > 4.5	Weekly dose of warfarin: Increases by 20% Increases by 10% the dose persists Reduces by 10% Skip until the MNI is <4.5, then continue treatment with a dose reduced by 20%

Measurement of MRI is carried out daily until a stable target level is reached, which is usually established on the 5th-6th day of treatment. Then, the MRI measurements are carried out weekly, reaching a 4-week interval. In the case of large deviations in the level of MND or in patients with liver disease or disease, the absorption of vitamin K affects the measurement intervals can be less than 4 weeks. The appointment of new or abolition of medications, previously accepted, requires additional measurements of PIM. With prolonged therapy, adjustments are made prior to a weekly dose of warfarin according to the table above. If the dose requires correction, the next PWR measurement should be done 1 or 2 weeks after the correction. After this, the measurements are continued until the 4-week intervals are reached.

Children: therapy with anticoagulants in children is conducted under the supervision of pediatricians. Doses are selected in accordance with the table below.

Day 1, if the spontaneous IPN from 1 to 1.3	Initial dose 0.2 mg / kg body weight 0.1 mg / kg of body weight if liver function is impaired
Days 2 to 4, if the value of the PIM: from 1.1 to 1.3 from 1.4 to 1.9 from 2 to 3 from 3.1 to 3.5 > 3.5	Maintenance dose Repeat the initial dose 50% of the initial dose 50% of the initial dose 25% of the initial dose Stop the drug before reaching the MRI <3.5, then resume treatment with a dose of 50% of the previous dose
Supportive treatment, if the value of PIM: from 1,1 to 1,4 from 1.5 to 1.9 from 2 to 3 from 3.1 to 3.5 > 3.5	Actions Increase the weekly dose by 20% Increase the weekly dose by 10% Without changes Reduce the weekly dose by 10% Stop the drug before reaching the MRI <3.5, then resume treatment with a dose, 20% less than the previous

Planned operations: pre-, post- and postoperative anticoagulant therapy is performed as described below.

Identify the PIM a week before the scheduled operation.

Stop taking warfarin 1-5 days before surgery. In the case of a high risk of thrombosis, low molecular weight heparin is administered subcutaneously to the patient for prophylaxis.

The duration of the pause in taking warfarin depends on the MRI. Acceptance of warfarin is discontinued:

• 5 days before surgery, if MNI> 4.0;
• 3 days before the operation, if the PIM = 3.0 to 4.0;
• for 2 days before surgery, if the PIM = 2.0 to 3.0.

Determine the MNI in the evening before the operation and enter 0.5-1.0 mg of vitamin K 1 orally or intravenously if MNI> 1.8.

Consider the need for infusion of unfractionated heparin or preventive 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 for concomitant reconstituted warfarin.

Continue taking warfarin with a regular maintenance dose on the same day in the evening after small surgeries and on the day the patient begins to receive enteral feeding after major surgery.

Adverse Reactions

The incidence of adverse reactions is as follows:

• very often (≥1 / 10);
• often (≥1 / 100, <1/10);
• infrequently (≥1 / 1000, <1/100);
• rarely (≥1 / 10000 to <1/1000);
• very rarely (<1/10000), the frequency is unknown (can not be determined from available data).

From the hemopoietic system and lymphatic system.

• Often hemorrhage.
• Infrequent anemia.
• Rarely coumarin necrosis, purpura finger syndrome, eosinophilia.
• Very rarely: vasculitis.

On the part of the respiratory system, thoracic and mediastinal disorders.

• Very rarely: calcification of the trachea.

From the digestive tract.

• Often, nausea, vomiting, diarrhea, pain in the abdomen.

From the digestive system.

• Very rarely: a reversible increase in the level of hepatic enzymes, cholestatic hepatitis, jaundice.

From the skin and subcutaneous tissue.

• Very rarely: alopecia, rash, eczema, urticaria, necrosis of the skin.

From the reproductive and urinary system.

• Very rarely priapism, nephritis, urolithiasis, tubular necrosis.

General disorders and reactions at the site of administration.

• Very rarely, allergic reactions (usually a rash), itching.

In the postmarketing period, the following adverse reactions were observed: fever, subdural hematoma, hemothorax, epistaxis, gastrointestinal bleeding, rectal bleeding, vomiting of blood, pancreatitis, ground, purpura, skin edema of the skin, which leads to ecchymosis, infarction and skin necrosis , hematuria, decrease in hematocrit.

Most often, reports (from 1% to 10%) about such an adverse reaction as bleeding develop in about 8% of patients taking warfarin annually. Moderate bleeding occurs annually in 6%, severe bleeding - in 1% and fatal - 0,25% of patients. A frequent risk factor for intracranial hemorrhage is untreated or uncontrolled hypertension. The likelihood of bleeding rises if MNI is significantly higher than the target level. If the bleeding started with PIM, which is within the target level, this means the existence of other attendant conditions that need to be investigated.

Coumarin necrosis is a rare (<0.1%) complication with warfarin therapy. Necrosis usually begins with swelling of the skin of the lower extremities or buttocks, darkened, but may appear elsewhere. Later such lesions become necrotic. 90% of these patients are women. The lesions are observed from the 3rd to the 10th day of admission and the etiology suggests an inadequacy of the antithrombotic protein C or S. Congenital insufficiency of these proteins can be the cause of complications. For this reason, the use of warfarin should be started simultaneously with the administration of heparin and in small initial doses. If a complication occurs, then warfarin is discontinued and heparin is continued until the lesions are healed or scarring.

The syndrome of the purple fingers is a rare complication when taking warfarin. This is typical for male patients with atherosclerotic diseases. It is suggested that warfarin causes hemorrhages of atheromatous plaques that lead to microemboli. There are symmetrical purple lesions of the skin of the fingers and soles of the feet, and such lesions are accompanied by burning pain. The use of warfarin should be discontinued, and skin lesions usually disappear.

Overdose

In cases of a gradual overdose, it is usually sufficient to stop taking the drug in order to reach the target level of MNI. In acute overdose, it is not recommended to empty the stomach because of the danger of bleeding. Reassign activated charcoal to prevent absorption and enterohepatic circulation of warfarin. When prescribing activated carbon, vitamin K, which may be needed later, should be administered parenterally (intravenously). In case of bleeding, the effect of warfarin can be stopped by the administration of vitamin K, a concentrate of coagulation factor or freshly frozen plasma.If oral anticoagulants are indicated in the future, larger doses of vitamin K than 10 mg should be avoided, as patients become resistant to warfarin for two weeks.

In overdose therapy, the following measures are taken:

In the absence of clinically significant bleeding
Level of PIM	Recommendations
<5.0	Skip the next dose of warfarin and restore the therapy to a lower dose when the target level of PSI is reached.
5,0-9,0	Skip 1-2 doses of warfarin and restore the therapy to a lower dose when the target level of MNI is reached or skip 1 dose of warfarin and prescribe vitamin K 1 2.5 mg orally.
> 9.0	Stop taking warfarin, prescribe vitamin K 1 from 3 to 5 mg orally.
A quick cancellation is shown (before the operation)
Level of PIM	Recommendations
5,0-9,0 and the planned operation	Stop taking warfarin and prescribe vitamin K 1 from 2 to 4 mg orally. Approximately 24 hours before the operation, an additional dose of 1 to 2 mg may be given orally.
Very quick cancellation is shown
Level of PIM	Recommendations
Severe bleeding or severe overdose (Eg, MHI> 20.0)	Assign vitamin K at a dose of 10 mg by slow infusion. Also, depending on the urgency of the situation, a freshly frozen plasma or a concentrate of the prothrombin complex is shown. If necessary, you can repeat the introduction of vitamin K 1 every 12:00.

Use during pregnancy and lactation

Warfarin penetrates the placenta. Therapy with warfarin in pregnant women can lead to warfarin embryopathy (nasal hypoplasia and chondrodysplasia) if warfarin is taken during organogenesis (from 6 to 12 weeks), and after that it can cause disorders in the development of the central nervous system. Warfarin can cause fetal hemorrhages, especially at the end of pregnancy and during labor. Warfarin embryopathy, as described, occurs in 4% to 6% of cases if warfarin is used during pregnancy and the likelihood of its occurrence is increased by taking a daily dose of more than 5 mg. Thus, warfarin is contraindicated in pregnancy. The risk of taking warfarin for the fetus should be carefully assessed relative to the risk to the mother in the event of the non-use of warfarin. Antithrombotic therapy during pregnancy should be carried out individually under the supervision of appropriate specialists.

Warfarin does not penetrate breast milk, so breast-feeding can continue during warfarin therapy.

Children

Therapy with anticoagulants in children is conducted under the supervision of pediatricians.

Application features

If it is necessary to quickly antithrombotic effect, it is recommended to begin treatment with the administration of heparin.After the administration of heparin, continue with simultaneous administration of warfarin for 5-7 days, until the MNI is maintained at the target level for at least two days.

During the administration of oral anticoagulants, reports of such an adverse reaction as bleeding are more often reported. Warfarin should be administered with caution to patients who are at risk of serious bleeding (eg, concomitant use of NSAIDs, after recent ischemic stroke, bacterial endocarditis, gastrointestinal bleeding).

The most likely risk factors for bleeding are high levels of anticoagulation (MHI> 4.0), age over 65 years, unstable MND, recent gastrointestinal bleeding, uncontrolled hypertension, cerebrovascular disease, serious heart disease, a tendency to fall, anemia, malignant tumor, trauma, renal failure, simultaneous intake of other medicines. All patients taking warfarin should regularly measure PIU. Patients with an increased risk of bleeding need frequent PID measurement, more careful selection of the dose to achieve the desired PIF and short duration of therapy. Patients should be warned about measures to minimize the risk of bleeding, and immediately inform the doctor of the appearance and symptoms of bleeding.

It is extremely important to measure PI, consult a doctor and reduce the dose or cancel the drug. If MNI is high, reduce the dose or stop therapy with warfarin. Sometimes it is necessary to continue therapy with anticoagulants. It should be vimyuvaty MNI for 2-3 days to make sure that it has decreased.

Other antiplatelet drugs should be used with extreme caution because of the increased risk of bleeding.

A mandatory condition for therapy with warfarin is strict adherence to the prescribed dose of the drug.

The occurrence of bleeding may indicate an overdose of warfarin. Unexpected bleeding when taking therapeutic doses should be examined and PIM should be monitored.

Anticoagulation after an ischemic stroke increases the risk of secondary hemorrhage to the brain. In patients with atrial flutter, long-term therapy with warfarin has been shown, but the risk of early re-embolism is low and therefore a break in treatment after ischemic stroke is justified. Treatment with warfarin should begin anew 2-14 days after ischemic stroke, depending on the size of the infarct and pressure. In patients with embolic strokes or uncontrolled hypertension, treatment with warfarin should be discontinued for 14 days.

Before surgery, if there is no risk of serious bleeding, surgery can be performed with MNI <2.5. Before surgery, if there is a risk of serious bleeding, taking warfarin should be stopped 3 days before surgery.

If it is necessary to continue anticoagulant therapy, for example, in thromboembolism, life-threatening, PIM should be reduced to <2.5 and heparin therapy is started.

If surgery is necessary and taking warfarin can not be stopped 3 days before surgery, anticoagulation should be canceled with low doses of vitamin K.

The recovery of warfarin therapy depends on the risk of post-operative bleeding.

The use of warfarin should not be discontinued before routine dental operations, such as tooth extraction.

Treatment of patients with peptic ulcer disease should be performed with extreme caution, given the high risk of bleeding. Such patients should be screened regularly and be informed about how to recognize bleeding, and, in the event of bleeding, that need to be taken.

Patients suffering from alcoholism, as well as patients with dementia may not be able to adhere to the necessary mode of taking warfarin.In the case of consuming large amounts of alcohol increases the risk of bleeding gipotrombinemii and development. Resistance to warfarin is very rare. Such patients to achieve a therapeutic effect needed from 5 to 20 conventional doses of warfarin. If warfarin is not sufficiently effective, must be set other probable reasons: lack of dosing, interactions with other drugs or food products, as well as laboratory error.

Patients with hereditary deficiency of antithrombotic protein C at the start of therapy with warfarin there is a risk of skin necrosis. In these patients, therapy should be initiated without a loading dose of warfarin, even if the patient is administered heparin. Patients with hereditary deficiency of protein S as an antithrombotic therapy with warfarin is recommended to start slowly.

Treatment of elderly patients should be performed with extreme caution. It is necessary to ensure the patient's ability to comply with strict rules while taking the drug. Hepatic metabolism, as well as the synthesis of clotting factors in the elderly is reduced. The result can easily occur excessive effect of warfarin. Treatment should be started with caution. It is necessary to take into account the concomitant medication in order to prevent unwanted interactions.

Many drugs and foods interact with warfarin and affect the prothrombin time. Taking any drugs including OTC drugs, it is the basis for the gain control of the PIM level. Patients should be warned about the need to inform the physician before taking any drugs, including herbal medicines and vitamin preparations.

Hyperthyroidism, fever and decompensated heart failure can increase the effect of warfarin. In hypothyroidism effect of warfarin can be reduced. In patients with moderate hepatic impairment warfarin enhanced. In case of renal failure, nephrotic syndrome or increased levels of free fraction of warfarin in the blood plasma, depending on concomitant diseases may lead to increased or decrease the effect of warfarin. In all these cases it is necessary to monitor the patient's clinical condition and the PIM level. Patients with mutations in the gene encoding the enzyme CYP2C9, have a longer half-life of warfarin. Such patients require lower doses, since the risk of bleeding when receiving usual therapeutic doses.

The influence of factors such as weight loss, acute disease, smoking cessation may increase the effect of warfarin and may require dose reduction.

Weight gain, diarrhea and vomiting, on the contrary, reduces the effect of warfarin, however increasing the dose may be required.

The preparation contains lactose. In rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose / galactose application of the drug is not shown.

To avoid the simultaneous application of cranberry juice and other products containing cranberries, because they significantly increase the effect of warfarin.

During therapy with warfarin intake of vitamin K from food should remain unchanged.

Most of all vitamin K is found in green vegetables and herbs, such as tea leaves (but not brewed tea), green amaranth, avocado, endive, peas, chayote, cabbage, green onions, kiwi fruit, coriander, peel cucumber (but not cucumber without skin), kale, lettuce, turnip, mint leaves, olive oil, broccoli, parsley, spinach, pistachios, red algae, onions, brussels sprouts, oil turnip, leaf mustard, soybeans, soybean oil, water cress.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Does not affect.

Interaction with other drugs and other interactions

Warfarin interacts with many other medications.

In a joint application with anticoagulants or hemostatic agent, the latter can enhance the pharmacological effect of warfarin, increasing the risk of bleeding. Streptokinase and alteplase contraindicated in patients receiving warfarin.

When warfarin should avoid taking thrombin inhibitors, not fractionated heparins, and their derivatives, heparin, low molecular weight, fondaparinux, rivaroxaban glycoprotein receptor antagonists, IIb / IIIa, prostacyclin, serotonin reuptake inhibitors, erlotinib, methylphenidate, oral contraceptives. If this is not possible, these drugs should be used with caution under close clinical and laboratory control

Absorption and enterohepatic circulation of warfarin may vary under the influence of certain drugs, such as cholestyramine. Available as induction (antiepileptic or anti-inflammatory drugs) and inhibition (amiodarone or metronidazole) effect of warfarin. In some cases, termination of the induction or inhibition of hepatic enzymes can also change the balance of warfarin therapy. Some drugs can displace warfarin from the compounds to plasma proteins, the free fraction increases and as a result, metabolism and excretion of warfarin are enhanced, resulting in reduced effect (except for patients with liver disease). Pharmacodynamic interaction observed during simultaneous administration with drugs affecting platelets (acetylsalicylic acid, clopidogrel, ticlopidine,dipyridamole, and the majority of non-steroidal anti-inflammatory drugs). The primary and secondary hemostasis in a patient can cause a strong tendency to bleeding. Penicillins in large doses have the same effect. Anabolic steroids, azapropazone, erythromycin, cephalosporins and some directly reduce the levels of vitamin K-dependent clotting factor synthesis and enhance the effect of warfarin. Vitamin K from food reduces the effect of warfarin. Reducing absorption of vitamin K, due, for example, diarrhea, can enhance the effect of warfarin. Patients who receive an inadequate amount of food with vitamin K, vitamin K dependent 2 products by intestinal microflora. In these patients, the majority of antibiotics may reduce the ability of intestinal flora to produce vitamin K 2,which leads to increased warfarin effect. Alcoholism associated with liver lesions potentiates the effect of warfarin. Quinine contained in water "Tonic", can also increase the effect of warfarin. Lactulose may enhance the effect of warfarin for prolonged use.

In the temporary need of analgesia in patients who receive warfarin is recommended to assign opiate or paracetamol.

Warfarin may enhance the effect of oral antidiabetic sulfonylurea derivatives.

The following drugs are known to alter the effect of warfarin:

Enhancing: allopurinol, amiodarone, amoxicillin, argatroban, aspirin, azapropazone, azithromycin, vitamin A, bezafibrate, dextropropoxyphene, digoxin, disulfiram, doxycycline, erythromycin, etoposide, vitamin E, fenofibrate, phenylbutazone, feprazone, fluconazole, fluorouracil, flutamide, fluvastatin, fluvoxamine, gatifloxacin, gemfibrozil, grepafloksatsin, ifosfamide, influenza vaccine, alpha- and beta-interferon, isoniazid, itraconazole, capecitabine, karboksiuridin, tsefamandola, cephalexin, cefmetazole, cefmenoxime, tse perazon, cefuroxime, ketoconazole, quinidine, quinine, clarithromycin, clofibrate, chloral hydrate, codeine, latamoxef, leflunomide, lepirudin, levofloxacin, lovastatin, metolazone, methotrexate, metronidazole, miconazole (also gel oral) moksalatam, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin,oxyphenbutazone, omeprazole, paracetamol (the effect is obvious after 1 -2 weeks of continuous use), proguanil, propafenone, propranolol, rofecoxib, roxithromycin, celecoxib, cimetidine, simvastatin, ciprofloxacin, sulfaphenazole, sulfafurazol, sulfamethizole, sulfamethoxazole-trimethoprim, sulfinpyrazone, sulfofenur , sulindac (anabolic or androgenic) steroids, cyclophosphamide, tamoxifen, tegafur, tetracycline, tolmentin, tramadol, trastuzumab, troglitazone, zafirlukast, nonsteroidal antiinflammatory drugs (NSAIDs) (the s as ibuprofen, ketoprofen, naproxen, diclofenac, indomethacin and piroxicam), (dextro) thyroxine, valproate.sulfaphenazole, sulfafurazol, sulfamethizole, sulfamethoxazole-trimethoprim, sulfinpyrazone, sulfofenur, sulindac (anabolic or androgenic) steroids, cyclophosphamide, tamoxifen, tegafur, tetracycline, tolmentin, tramadol, trastuzumab, troglitazone, zafirlukast, nonsteroidal antiinflammatory drugs (NSAIDs) (such as ibuprofen, ketoprofen, naproxen, diclofenac, indomethacin and piroxicam), (dextro) thyroxine, valproate.sulfaphenazole, sulfafurazol, sulfamethizole, sulfamethoxazole-trimethoprim, sulfinpyrazone, sulfofenur, sulindac (anabolic or androgenic) steroids, cyclophosphamide, tamoxifen, tegafur, tetracycline, tolmentin, tramadol, trastuzumab, troglitazone, zafirlukast, nonsteroidal antiinflammatory drugs (NSAIDs) (such as ibuprofen, ketoprofen, naproxen, diclofenac, indomethacin and piroxicam), (dextro) thyroxine, valproate.(Dextro) thyroxine, valproate.(Dextro) thyroxine, valproate.

Reducing the Effects of azathioprine (barbiturates), vitamin C, dikloksatsilin, disopyramide, phenobarbital, griseofulvin, carbamazepine, kloksatsilin, chlorthalidone, chlordiazepoxide, mercaptopurine, mesalamine, mitotane, naftsilin, nevirapine, primidone, rifampicin, tacrolimus, spironolactone, trazodone.

Herbal treatments may also increase the effect of warfarin, e.g., ginkgo extract (Ginkgo biloba), garlic extract (Allium sativum), drugs dong quai (Angelica sinensis, contains coumarins), papaya extract (Carica papaya) or Danchin (Salvia miltiorrhiza), or decrease it, e.g., ginseng (Panax spp.), or Hypericum perforatum extract (Hypericum perforatum). This is due to the ability to induce Hypericum enzymes metabolize drugs. Therefore, herbal preparations containing St. John's wort is not recommended to be taken with warfarin. The effect can continue for 2 weeks after stopping the drugs of plant origin. If a patient is already taking St. John's wort extract, you need to measure PIM level and stop taking St. John's wort extract.Because PIM can increase cases of hypericum extract, it should be carefully monitored. It may be necessary to adjust the dose of warfarin.

Pharmacological properties

Pharmacodynamics.Warfarin or 4-hydroxycoumarin - anticoagulant that blocks the vitamin K-dependent blood clotting factor synthesis. With its isomer S-warfarin about 5 times stronger than R-warfarin. Its efficiency is based on warfarin ability to block the effect of vitamin K on the synthesis of the blood clotting factors II, VII, IX and X. In therapeutic doses of warfarin reduces the rate of synthesis of clotting factors by 30-50% and also reduces their biological activity. Full effect occurs at 2-7 days (during this time, clotting factors, are already circulating in the blood removed from the body).

Pharmacokinetics. After oral administration, the bioavailability of warfarin is higher than 90% and the maximum concentration in blood plasma is achieved after 1.2 hours. Simultaneous food intake slows down absorption, but does not reduce absorption quantitatively, due to the presence of hepatic circulation. Warfarin almost completely binds to albumin, the free fraction varies from 0.5% to 3%. The volume of distribution is approximately 0.14 l / kg. Warfarin penetrates the placenta, but does not penetrate into breast milk. Warfarin is metabolized in the liver by catalysis of CYP2C9 (S-warfarin), CYP1A2 and CYP3A (R-warfarin), it turns into inactive metabolites that are excreted in the urine.The half-life of S-warfarin is 18-35 hours, and R-warfarin is between 20 and 70 hours.

Basic physical and chemical properties

tablets of 3 mg round tablets with a flat surface with bevelled edges and a notch, light blue, with possible impregnations.The surface of the tablets contains the imprint "ORN 17" on one side;
tablets of 5 mg tablets of round shape with a flat surface with bevelled edges and a notch, pink color, with possible impregnations. The surface of the tablets contains an imprint of "ORN 18" on one side.

Shelf life

3 years.

Storage conditions

Store at 15-25 ° C. Keep out of the reach of children.

Packaging

For 30 or 100 tablets in a vial; 1 bottle in a cardboard box.

Category of leave

On prescription.