Taking warfarin - INR norm, dose, diet, contraindications and reviews

Even if the doctor explained in detail what dosage to take Warfarin, the instructions for use should still be thoroughly studied by the patient. This drug has an indirect effect directly on blood clotting, that is, it acts as an indirect anticoagulant. The peak effect occurs 3-5 days from the start of use. The action of the tablets, at the correct dosage, is aimed at the synthesis of side enzymes that regulate blood clotting, but thrombin is not affected at all.

Historical reference

In the early 20s, an outbreak of a hitherto unknown bovine disease was registered in the United States, and later Canada. Cows often began to spontaneously bleed; for example, after dehorning, 24 out of 25 animals died. The gap also affected males - only 14 out of 30 bulls survived the castration procedure. The reason for the increased mortality was simple blood loss.

The secret of the disease was discovered by butcher-pathologist Frank Schofield in 1921. He found out that the dead animals ate moldy silage from sweet clover, which is a powerful coagulant. To confirm his theory, he conducted an experiment with rabbits, giving one group of individuals spoiled hay and the other fresh hay. The moldy stems of the plant caused multiple bleeding in animals and led to death. After 8 years, veterinarian Roderick L.M., based on experiments, revealed that their condition was directly related to the insufficient functioning of prothrombin.

Warfarin is prescribed to patients for life while monitoring blood clotting

Unfortunately, the anticoagulant substance from sweet clover could not be isolated until 1940. After synthesis, it received the name dicumarol. It was obtained from plant coumarin molecules. It is its sweetish smell that we feel when inhaling the aroma of freshly cut grass. Dicumarol became the first anticoagulant patented in 1941. The drug Warfarin was synthesized after 7 years. And the history of its origin is no less interesting.

Warfarin was first officially registered and used as an effective poison to kill rodents. But doctors began to think about a more useful use of the drug after an incident with a US military conscript who tried to commit suicide with the help of this substance. He was taken to intensive care and treated with an increased dose of vitamin K, resulting in a full recovery. Doctors noticed that the use of Warfarin in the doses indicated in the instructions inhibits an enzyme called epoxide reductase, disrupting general metabolism and having a powerful effect on blood viscosity.

After this, studies began on the use of a drug containing Warfarin as a therapeutic anticoagulant. It is noteworthy that one of the first patients to receive these pills was President Dwight Eisenhower, who survived a heart attack. There is a theory that it was with Warfarin that his closest associates tried to poison even Joseph Stalin himself; the substance has no color or taste and, according to the symptoms of its effects, completely coincides with the clinical picture that appeared in the dictator.

Pharmacokinetics of the drug

After use, Warfarin is absorbed into the stomach almost completely. It binds to liver proteins by 97-99%. According to the instructions, the substance is also metabolized in liver cells.

Warfarin Nycomed is a racemic mixture, but the R- and S-isomers are metabolized separately. They form 2 different metabolites.

The catalyst for the S-enantiomer is the enzyme CYP2C9, respectively, for the R-enantiomer it is CYP1A2 and CYP3A4. The levorotatory isomer has approximately 2-5 times increased anticoagulant activity (according to the attached instructions). If a patient experiences a polymorphism of the CYP2C9 enzyme after using the substance, then he may have too much sensitivity to the active substance Warfarin, which increases the risk of internal bleeding.

According to the instructions, after use, Warfarin is safely excreted from the human body along with urine (with bile). The process takes from 20 to 60 hours after the end of the reception. In this case, the R-enantiomer may require up to 90 hours, and the S-enantiomer only 44 hours.

pharmachologic effect

warfarin formula

Warfarin is included in the list of indirect anticoagulants. It blocks the activity of the enzyme necessary for the formation of vitamin K, which, in turn, helps the synthesis of individual coagulation factors - II, VII, IX, X, as well as some proteins. As a result of the drug's action, the vitamin K-dependent pathway for the production of coagulation factors is disrupted, and the higher the dosage, the more pronounced the inhibitory effect of warfarin on hemostasis.

In recommended therapeutic doses, the drug reduces the total amount of active factors and vitamin K by about a third and up to half. The effect of taking it appears within a day from the start of treatment, but it reaches its maximum after 3-4 days, lasting for a total of up to five days. With daily regular use of the drug, its effect becomes stronger.

Warfarin does not act directly on a blood clot and, moreover, does not restore tissue in areas of ischemic damage, but its administration is necessary to ensure that there is no increase in the volume of thrombotic deposits or the detachment of their fragments with the development of embolism.

The drug is taken orally, after which it is almost completely absorbed in the intestine, and already in the first four hours after consuming the anticoagulant, its maximum amount is found in the blood, associated with plasma carrier proteins. The drug is able to pass through the placental barrier, after which its concentration in the fetal blood becomes almost the same as in a pregnant woman, but does not penetrate into breast milk.

Active warfarin from the blood enters hepatocytes, where it is inactivated. The end products of drug metabolism enter the urine through the renal filter and are excreted from the body. In addition, some of the inactive components may be excreted in the bile.

In elderly patients after 60 years of age, the ratio of prothrombin time to INR changes more than in young patients, so the main blood-thinning effect of the drug will be more noticeable. This feature requires dosage adjustment with taking a smaller amount of the drug in older patients.

Pregnant women should not be prescribed warfarin, as it penetrates into the bloodstream of the developing fetus, reaching a therapeutic “adult” dose, which can lead to bleeding. In addition, some studies indicate a teratogenic effect of the anticoagulant. It practically does not penetrate into breast milk, but experts advise babies feeding from a mother being treated with warfarin to determine the INR. If it is necessary to use high dosages of the drug, it is advisable to stop breastfeeding.

In case of kidney failure, the effect of the anticoagulant practically does not change, which is associated with the excretion in the urine of an already inactivated drug, the circulation of which in the blood does not cause coagulation disorders. This circumstance is associated with the prescription of the same dose of the drug for renal failure as for all other patients.

Unlike the kidneys, the liver can reverse the effects of warfarin. Thus, hepatocyte deficiency increases the concentration of active forms of the drug and the formation of natural anticoagulants, which inevitably leads to an increase in the effect of the drug, so patients with pathology of the hepatic parenchyma may need to reduce the dosage of warfarin.

The route of administration of the drug is not critical for maintaining the required concentration of the drug and obtaining a therapeutic effect. Both when administered intravenously and when tablets are taken orally, an equal amount of its active forms circulates in the blood. Intravenous administration allows you to quickly achieve the maximum concentration of warfarin in plasma, but the anticoagulant effect in both cases will not occur earlier than after 3-4 days.

Admission rules

Warfarin is often prescribed to patients for life. But in order for the treatment to bring only benefits, you should adhere to a number of simple rules described in the instructions:

• regularly take blood tests to monitor blood clotting indicators;
• take Warfarin of the same brand;
• adhere to the diet prescribed by the doctor, which usually includes a large number of foods containing vitamin K (cabbage with dark green leaves, salad);
• exclude cranberry juice from the diet (it is also contraindicated in the instructions);
• Closely monitor bleeding (for example, while brushing your teeth or during menstruation) and bruising and report them to your doctor;
• Under no circumstances should you change the dosage of Warfarin yourself;
• consult a doctor and follow the instructions before starting parallel intake of vitamins, dietary supplements or herbal infusions (teas, decoctions);
• limit the consumption of alcoholic beverages;
• at an appointment with a doctor (dentist, etc.), inform him that you are a patient taking Warfarin;
• If you experience any side effects related to your health, contact your doctor immediately.

Manufacturers and possible dosage of tablets

Warfarin, the tablet of which may differ in dosage, is produced by several European and domestic factories. The most common drugs in the pharmacy chain are from Orion Corporation (manufactured in Finland), Pharma Start (Ukraine, the most budget option), Takeda Pharma (Denmark or Poland). Instructions for the medication are always included.

The medicine Warfarin is available in the following forms:

• FS tablets of 2.5 and 3 mg (packaged in bags, containers);
• tablets No. 10 and No. 100 (this is how the number of units in the blister is indicated);
• Warfarin Sodium Clathrate is a white or colorless powder in double packaging, intended and directly used for the production of solutions and non-sterile dosage forms;
• Warfarin Nycomed - most often packaged in 100 tablets with a dosage of 2.5 mg;
• Orion - tablets containing 3 and 5 mg of the active substance (30 pieces per package), in liquid form have a volume of 100 mg (bottle).

This drug is not available in the form of suppositories or ampoules. The use of the active substance in this way is not intended.

Warfarin analogs

For patients who have previously successfully used Warfarin in their treatment and prevention of blood clots and have not observed changes in INR levels, there is no point in switching to another drug. This may only be required directly if the instructions identify direct contraindications and the risk of bleeding is too great. For replacement, the doctor may prescribe the following medications:

• Dabigatran (Ethexilate);
• Heparin injections are very effective; low molecular weight options are also used, for example, Enoxaparin (Clexane);
• Aspirin (Astrid, Cartia);
• Rivaroxaban (Xarelto, according to the instructions, they are completely identical in action);
• Dipyridamole (imported names - Asasantin Wed, Persantin Wed);
• Apixaban (Eliquis will need to adjust the dosage, it may differ from the original instructions);
• Clopidogrel (you can find Plavix, Iskover in the pharmacy).

Interestingly, these medications rarely require INR and PRI monitoring. However, according to the instructions, they have a number of dangerous side effects, which are recommended to be discussed with your doctor before using the medicine.

Side effects and overdose of anticoagulant

Side effects from taking warfarin can be very serious and even life-threatening, so the doctor carefully ascertains the patient’s contraindications, and the patient himself would do well to read the list of them in the instructions for the drug.

The anticoagulant effect causes increased bleeding, up to massive bleeding. This is the most common adverse effect of the drug. In addition to bleeding, the following are possible:

• Increased sensitivity to the anticoagulant with prolonged use;
• Anemia;
• Dyspeptic symptoms - nausea, diarrhea, vomiting and abdominal pain;
• Rarely, but still not excluded, allergic reactions such as urticaria, itching, jaundice of the skin, increased serum levels of liver enzymes AST and ALT, kidney damage, hair loss and eczematous skin changes.

Bleeding occurs in approximately 8% of patients taking the drug for at least a year. They may require hospitalization and infusion of blood and blood components, but fatal bleeding is still rare. Of particular danger is increased bleeding in patients suffering from hypertension, which is not treated or responds poorly to antihypertensive therapy. In these cases, there is a high risk of intracranial hematoma (hemorrhagic stroke).

A specific, albeit rare, complication of taking warfarin is skin necrosis, which manifests itself as swelling and darkening of the skin of the legs and buttocks, which culminates in the formation of foci of tissue necrosis. Every ninth patient with this complication is a woman.

Necrotic changes occur from the third to the 10th day of treatment. In order to neutralize hemostatic disturbances in persons predisposed to necrosis, warfarin is prescribed with heparin, and in cases where necrosis has already appeared, warfarin is discontinued, and heparin administration is continued until the lesions are completely scarred.

Men suffering from atherosclerosis may experience another rare complication - hand-foot syndrome, which manifests itself in the hands and feet with severe pain and symmetrical purple rashes. It is assumed that the reason for everything is hemorrhages into atherosclerotic plaques with microthromboembolism. Canceling the medication leads to a gradual disappearance of negative symptoms.

Factors that may increase the likelihood of bleeding while taking warfarin are older age, concomitant intensive anticoagulant and antiplatelet therapy, previous strokes and bleeding from the stomach and intestines.

An overdose of warfarin is manifested mainly by bleeding, but it is worth noting that effective treatment may be accompanied by minor bleeding - gingival bleeding, microhematuria, which do not require discontinuation of the drug or dose reduction if the amount used maintains the target INR level.

To treat bleeding in case of overdose in mild cases, reduce the dosage or completely stop the drug for a while. For severe bleeding, the use of intravenous vitamin K, enterosorbents, infusion of fresh frozen plasma and coagulation factors is indicated.

Pharmacotherapeutic action and indications for use

Warfarin Nycomed, according to the instructions, has an anticoagulant effect. It is aimed at significantly slowing down or completely inhibiting the synthesis of factors that are associated with blood coagulation in the liver, which occurs under the influence of vitamin K. But it should be understood that according to the instructions, the drug is an indirect anticoagulant, so during use it does not cause clotting directly in the blood channel, but begins to act only a couple of days after administration.

Warfarin's instructions for use are quite extensive. The drug must be prescribed to people at risk of developing embolism or blood clots. Under the supervision of a doctor and in accordance with the instructions, the medicine can be prescribed for the following diagnoses:

• varicose veins – varicose veins in the legs or torso;
• thrombophlebitis – veins are contaminated with harmful cholesterol;
• acute or chronic venous thrombosis (take according to individual dosage);
• secondary myocardial infarction (Warfarin is prescribed for life);
• a blood clot formed in the lungs (pulmonary embolism);
• thrombosis of cerebral or peripheral or coronary arteries;
• haemorrhoids;
• thromboembolism;
• transient ischemic attacks that develop into strokes - especially if there is a risk of death.

Warfarin Nycomed is often taken in the postoperative period, when the body is full of medications designed to stop bleeding. When replacing heart valves and blood vessels, the medication is often combined with acetylsalicylic acid, according to the instructions.

Warfarin is prescribed in the postoperative period to prevent bleeding

Use (effect) of warfarin, dose, overdose

The body needs vitamin K to ensure blood clotting.

A person gets vitamin K from food, mainly from vegetables. Vitamin K can also be produced in the human intestine by special intestinal bacteria. From the intestines, vitamin K is absorbed into the blood and goes to the liver, the “laboratory” of the body. In the liver, with the participation of vitamin K, blood clotting factors necessary for the formation of a blood clot (thrombus) are synthesized. These are prothrombin (factor II), factors VII, IX and X. They are called “vitamin K-dependent factors”.

The action of warfarin is to reduce the formation of vitamin K-dependent factors. As long as warfarin is regularly injected into your body, your blood's clotting time is prolonged and this prevents blood clots from forming. There is also a risk of bleeding if the dose of the drug is excessive.

The effect of warfarin on blood clotting varies from person to person.

Therefore, each patient receives his own, individually selected dose. To achieve the desired effect, a minimum of 4-5 days is required, often dose selection lasts up to 2-3 weeks. Prescription of the drug and further monitoring are carried out using the determination of INR. The daily dose of warfarin is taken orally once a day, in the evening (at 18.00-19.00 hours); if necessary, the tablet or part of it can be chewed and washed down with water.

What should you tell your doctor about if you start taking warfarin or are already being treated with it?

About all problems associated with bleeding or its risk (stomach or duodenal ulcers, colon; hemorrhoidal bleeding; heavy menstruation), liver and kidney diseases, high blood pressure and diabetes. Very important if you are planning a pregnancy or are already pregnant. Warfarin has a teratogenic effect. This means that taking it can lead to various deformities in the fetus (if taken in the first trimester of pregnancy) or to intrauterine bleeding (in later stages). Therefore, women whose pregnancy occurred while taking warfarin are recommended to terminate it.

Contraindications and dangers of the drug

The instructions included with Warfarin also describe a number of contraindications to the use of the drug. For example, it should not be used by patients prone to bleeding and suffering from anemia. Warfarin is contraindicated in the following cases:

• bacterial endocarditis;
• pregnancy (Warfarin is strictly prohibited in the 1st trimester and in the last 4 weeks of pregnancy);
• lactation period at any age of the child (breastfeeding);
• acute syndrome (stages 2 and 3) of disseminated intravascular coagulation;
• clearly visible aneurysm;
• lumbar puncture (prohibited in any cases);
• period of menstruation;
• deficiency of category C and S proteins (strictly prohibited in the instructions);
• cerebrovascular hemorrhages;
• peptic ulcer of the walls of the stomach, any part of the gastrointestinal tract or damage to the duodenal mucosa;
• malignant (or turning into a cancerous tumor) arterial hypertension;
• thrombocytopenia (prohibited in the instructions);
• severe arterial hypertension;
• exudative and no less dangerous bacterial pericarditis;
• liver or kidney failure;
• hemorrhagic stroke, intracranial hemorrhage caused by injury or disease;
• varicose veins affecting the veins located in the esophagus.

You should not take the drug to patients who cannot take blood tests exactly on schedule to monitor the level of blood clotting. According to the instructions, Warfarin is prohibited for people who are unable to independently control the dosage and strictly follow the doctor’s recommendations.

The use of the drug is not prescribed for recent ophthalmological (performed on the eyes) and craniocerebral operations, as well as for extensive surgery in the torso area (chest, back, abdominal area). The medicine is also dangerous for patients with hypersensitivity to Warfarin.

Contraindications to warfarin

Some people have contraindications to the use of “indirect” anticoagulants (warfarin):

1. Individual intolerance or allergy.
2. The presence of diseases and conditions that are potentially dangerous for the development of bleeding:

• intracerebral aneurysms and vascular malformations;
• recent injury or major surgery;
• peptic ulcer of the stomach or duodenum in the acute stage;
• vitamin K hypovitaminosis;
• alcohol abuse;
• portal hypertension with esophageal varices;
• impaired renal function (creatinine level in the blood - more than 200 mmol/l);
• impaired liver function with a more than threefold increase in the level of liver transaminases;
• high arterial hypertension, resistant to drug treatment (BP level > 160/100 mm Hg);
• thrombocytopenia (low levels of platelets in the blood);
• the need for constant use of non-steroidal anti-inflammatory drugs;
• malignant neoplasms.

3. History of hemorrhagic complications:

• active bleeding of any location;
• hemorrhagic stroke;
• bleeding from the gastrointestinal tract;
• hemorrhagic diathesis;
• gross hematuria;
• metrorrhagia in menopausal women.

First aid for different types of bleeding

4. Inability to adequately control therapy:

• history of severe central nervous system disorders;
• dementia (including in older people);
• lack of laboratory control over the level of anticoagulation.

How to take Warfarin?

When starting to take Warfarin Nycomed, you must read the instructions for use. But it is equally important to get a personal diary with a table. It is convenient to note changes in the dosage of the drug and maintain an exact schedule for its daily intake. Warfarin is taken at the same time every day!

Your doctor will tell you in detail how to take the medicine. The tablet can be taken both before and after meals. It must be swallowed whole with a sufficient amount of liquid. Do not chew or crush the pill in any other way.

Compatibility of drugs with warfarin

Warfarin can be taken at the same time as other medicines. Never change the dose yourself or take a double dose! If you forget to take the drug, take it as soon as you remember. Tell your doctor at your appointment if you miss a dose. How to properly take other medications with warfarin:

Remember that there are other medicines that are not included on this list. Check with your doctor.

PTI and INR, analysis directly while taking the medicine

Before prescribing Warfarin, the doctor must monitor IPT and INR:

• INR is an abbreviation for international normalized ratio, which stands for the ratio of the prothrombin time of a specifically selected person (that is, the patient) to the standard prothrombin period;
• PTI stands for prothrombin index, which allows you to compare the ratio of prothrombin time in an absolutely healthy person with the exact indicators of the selected patient.

According to the instructions, it is advisable to undergo both tests before use. The PTI norm ranges from 70-100 units. Warfarin Nycomed is able to reduce this figure to 24-26 units. It is dangerous when this parameter is higher, this indicates that the patient has a high risk of developing a stroke. If the level is too low, severe bleeding can occur, which can be fatal.

Blood INR - what is the norm?

How do doctors determine blood's ability to clot?

To do this, a blood test is performed - prothrombin time. Previously, doctors received the result of this analysis in the form of prothrombin index (PTI). Currently, all over the world, the laboratory produces the result of a prothrombin time study in the form of INR - international normalized ratio. All healthy people not receiving warfarin have an INR within one (0.9-1.1). As blood clotting time increases, the INR value increases. For example, to prevent thrombosis in chronic atrial fibrillation, it is necessary to lengthen the coagulation time by 2-3 times. In this case, the INR should be within the therapeutic range of 2.0-3.0. When implanting artificial heart valves, the interval shifts towards greater “thinning” of the blood - from 2.5 to 3.5. Your doctor will tell you what INR goals you need to adhere to.

Detailed instructions for use

To get only benefits from the medication for the body and avoid unpleasant side effects, you should follow a number of simple rules:

1. Before starting treatment, the patient must undergo an INR and PTI test. Repeated testing is carried out every 4-8 weeks, which allows you to monitor the condition of the blood. In this case, the therapy itself may already be completed.
2. Warfarin Nycomed is taken 1 time per day, strictly according to the instructions at the same time.
3. The duration of the required treatment period is determined by the doctor individually and directly depends on the severity of the disease and the general condition of the patient.
4. If the patient has previously used Warfarin, he is usually prescribed a starting dose equal to twice the maintenance dose. The course of treatment with this regimen is 2 weeks.
5. On day 5, immediately after starting to take the pills, the patient must undergo an additional INR test. Based on its results, the doctor adjusts the dosage and duration of treatment as a whole, taking into account the recommendations from the instructions.
6. When INR levels are high (2.5-3.5 units), Warfarin continues to be used only for complicated myocardial infarction and after heart valve replacement surgery.

If the patient has not previously had to deal with Warfarin, then he is prescribed an initial dosage. Usually it is 2 tablets. Primary treatment is carried out over 4 days. After passing the INR analysis, the dosage is adjusted according to the instructions from 1 to 3 tablets according to the schedule for every 24 hours.

If the INR is between 2 and 3, the prescription and subsequent use of Warfarin is permitted only for the following diagnoses:

• therapy and prevention of pulmonary embolism;
• atrophy of heart valves;
• venous thrombosis (there are contraindications in the instructions);
• prosthetics (a technique requiring surgical intervention) of the heart valve using bioprostheses;
• dilated cardiomyopathy;
• atrial fibrillation.

I'm taking warfarin and I have bruises, what should I do?

The higher the INR level, the lower the blood's ability to clot. Within the therapeutic INR interval, the risk of bleeding is minimal. Therefore, your doctor recommends that you have an INR blood test at least once a month to make your treatment as safe as possible. You will also be warned about the first signs of bleeding, which may indicate a risk of bleeding: bleeding gums when brushing your teeth, the appearance of brown urine (the color of “meat slop”), unusually large bruises. In this case, you need to see a doctor as soon as possible and take an emergency INR test. You may have to reduce your warfarin dosage and you won't get any new bruises.

If you start bleeding:

nasal infections, coughing up blood, heavy and prolonged menstruation, black stools (except when taking medications containing iron - for example, to treat anemia), dizziness and disturbances in speech, movement and sensitivity of the arms and legs, red or dark brown urine, vomiting " coffee grounds" - temporarily stop taking the drug and immediately contact your doctor.

How to behave in everyday life, and is it necessary to limit activity?

You should be careful in situations where there is a risk of injury (bruise, abrasion, cut, etc.). In these cases, you will bruise more easily than usual and will take longer than usual to stop bleeding. For shaving, it is better to use an electric razor, brush your teeth with a soft brush and be careful when using dental floss. If you are injured, you must inform emergency personnel about taking the drug. Your loved ones should also know that you are taking warfarin so that if necessary, they can inform their doctors about it.

In cases where dental treatment (tooth extraction) or minor surgery is necessary, your doctor will reduce the dose of warfarin to the lower limit of the therapeutic interval of INR 2.0. If more complex operations are required, your dose will be adjusted individually or, more likely, you will be temporarily switched to another drug (for example, heparin).

Remember that warfarin treatment can prevent thrombosis that threatens your life and health, and the safety of treatment depends, first of all, on you and your contact with doctors.

• Take the drug strictly as prescribed by your doctor.
• Maintain a regular schedule of INR blood tests and a diet with consistent amounts of vitamin K.
• Watch for signs of bleeding and tell your doctor right away if you notice any.
• Inform all your doctors that you are taking "indirect" anticoagulants.

Be healthy!
Leave your feedback on the use of this drug. Perhaps they will help other people. According to warfarin.ru

Taking Warfarin in old age

There are no special recommendations for elderly patients when using Warfarin. But treatment with this drug should be carried out exclusively under the constant supervision of the treating doctor and in compliance with the instructions, since with age the risk of developing various side effects increases significantly.

The instructions indicate that when used simultaneously with anticholinergic drugs, memory impairment and absent-mindedness may occur. And when combined with hypoglycemic drugs, the effect of the latter is enhanced.

Compatibility of warfarin with other drugs and precautions during treatment

When using warfarin and any other medicine simultaneously, you should definitely discuss this with your doctor, since if the compatibility of the drugs is violated, the risk of adverse reactions and serious complications increases significantly.

The likelihood of severe bleeding increases when warfarin is used concomitantly with:

1. Aspirin;
2. Clopidogrel;
3. Ticlopidine;
4. Chimes;
5. Non-selective anti-inflammatory drugs (except COX-2 inhibitors);
6. Penicillin antibiotics in high dosage;
7. Cimetidine (replaced with ranitidine or famotidine);
8. Chloramphenicol.

The listed drugs affect platelet count and blood clotting, so it is better not to combine them with anticoagulants, but aspirin is sometimes prescribed along with warfarin, and the INR level should not exceed 2.5.

A number of drugs can enhance the effect of warfarin: aspirin, amiodarone, sumamed, ofloxacin and many other antibacterial and antifungal agents, vitamins A and E, heparin, some beta blockers, lipid-lowering drugs and cardiac glycosides (digoxin, clofibrate, propranolol), antidepressants (amitriptyline , rexetine, sertraline, fluoxetine), steroid hormones and non-steroidal anti-inflammatory drugs. A complete list of medications that enhance the effect of warfarin is given in the instructions for use of the drug.

Video: about the incompatibility of warfarin with other drugs

In addition to medications, the anticoagulant activity of warfarin increases with alcohol intake, which should be avoided for the entire duration of treatment, as well as drinks containing quinine as a tonic additive.

In addition to synthetic drugs, many herbs influence the metabolism of warfarin, which adherents of traditional medicine should be warned about. Thus, garlic, papaya, and sage increase the anticoagulant effect, while St. John's wort and ginseng reduce it.

Particular care should be taken when taking St. John's wort. Under the control of INR, St. John's wort preparations are discontinued, but hemostasis indicators are carefully monitored, since a decrease in coagulation is possible when stopping the use of St. John's wort. The effect of St. John's wort lasts approximately 2 weeks after its discontinuation, during this period the INR is monitored and only after normalization of hemostasis is it possible to prescribe warfarin.

Many drugs can reduce the effectiveness of warfarin - phenobarbital, azathioprim, vitamins K and C, carbamazepine, veroshpiron, cyclosporines and others. When used together, the INR should be regularly checked and treatment adjusted.

To avoid negative consequences from taking warfarin, the patient must take a strictly prescribed dose of the drug. For alcoholism and dementia, warfarin is not contraindicated, but patients may violate the treatment regimen established for them, which is fraught with serious consequences.

During treatment with anticoagulants, the patient should monitor his diet, if possible eliminating or reducing the proportion of foods that weaken or increase the procoagulant properties of the drug. For example, foods containing large amounts of vitamin K can reduce the effectiveness of warfarin, while diarrhea and laxative use can increase it.

The diet when taking warfarin involves the exclusion or significant limitation of vitamin K-containing foods: greens, cabbage of various varieties, peas and soybeans, spinach, leafy salads (lettuce, watercress), and olive oil are not recommended.

Video: what products warfarin cannot be combined with

Today, a number of warfarin analogues have been obtained, which replace the anticoagulant. Some of them involve systematic clarification of the INR level, while others do not require such control. Determination of hemostasis parameters is necessary when replacing warfarin with a cheaper analogue containing the same active substance - warfarex, marevan. These products have a large list of contraindications and adverse reactions indicated in the instructions.

There is a group of anticoagulants with an effect similar to warfarin, but which do not require systematic determination of INR, which simplifies the life of patients. Analogues that do not require INR control include clopidogrel, phenylin and the new generation drugs Pradaxa and Xarelto. They are more effective than warfarin and can be used in combination with it to prevent recurrent episodes of blood clots in the arteries.

The compatibility of warfarin with the treatment the patient is receiving is determined by the attending physician. If necessary, it is possible to either replace it with another anticoagulant with no less effectiveness, or cancel or replace other drugs with analogues that do not change the effect of warfarin.

Recommendations for patients with renal and liver failure

There are no special contraindications or recommendations in the instructions for use for patients with renal failure. Even if a person is on peritoneal dialysis, he should not increase the dose of the drug without additional advice from a doctor.

With liver failure and other liver problems, patients experience increased sensitivity of the body to Warfarin. Before taking the drug, you should consult your doctor. It is the liver that metabolizes Warfarin, and it, in turn, has a direct effect on the level of blood clotting. Therefore, people with liver failure should strictly monitor their INR.

How and in what quantity is warfarin prescribed?

The instructions for use of warfarin explain in detail how and in what quantities it is permissible to take the drug. Most often it is prescribed in tablets, once a day every day, preferably at the same time (usually 17:00), so that the intervals between tablets are approximately the same. The duration of therapy is determined by the attending physician.

Before starting treatment, possible contraindications are carefully assessed, and the INR (international normalized ratio), which characterizes the state of hemostasis, is determined. When taking warfarin for a long time, the INR must be constantly monitored by testing at least once a month. If necessary, the drug can be discontinued immediately, without a period of dosage reduction.

The target indicators of blood clotting during treatment with warfarin are considered to be an increase in prothrombin time up to 4 times, an INR in the range of 2.2-2.4 , depending on the nature of the pathology, the likelihood of thrombosis and bleeding.

If the patient has never used warfarin before, then the initial dose is 5 mg per day for the first four days of treatment. On day 5, the patient donates blood for an INR test, depending on the values ​​of which the maintenance dosage is determined, usually up to three tablets (up to 7.5 mg per kg of weight).

In cases where there is already experience in using an anticoagulant, the doctor prescribes a starting dose for the first two days of use, which is double that taken previously. From the third day, therapy is carried out with the maintenance dose that the patient has already taken. On day 5, the INR is determined and, if necessary, the amount of medication is adjusted.

For the prevention and treatment of thrombus formation in the veins, pulmonary embolism, arrhythmia, damage to the heart valves, as well as after transplantation of biological valves, the recommended INR value is within 2-3 .

With a higher risk of thrombosis after transplantation of synthetic valves, in the case of complicated forms of myocardial infarction, the INR should be higher - 2.5-3.5 .

Children are a special category of patients whose use of warfarin is limited and is carried out under the strict supervision of a physician. The starting dose is 0.2 mg per kg daily if the liver is functioning normally, otherwise it is halved to 0.1 mg/kg. The maintenance dosage is set depending on blood clotting parameters. The target INR level for treatment is the same as for adult patients.

At each stage of the child taking warfarin, clotting is monitored and the dose of the medication is adjusted. As the INR increases, it decreases until it is completely canceled when it exceeds 3.5, and then the intake continues in a reduced amount.

Elderly patients often take warfarin tablets for a long time and even for life; there are no specific recommendations (except for a possible dose reduction) for therapy in this category of patients, however, constant monitoring is the key to safe treatment, since the risk of adverse reactions increases with age.

Disorders of the liver can change the effect of the drug, since the organ synthesizes coagulation factors, but with pathology there are fewer of them, and sensitivity to warfarin is higher. The dose is selected according to the INR and is often lower than that prescribed in accordance with age and pathology.

Kidney disease, on the contrary, does not in any way affect the anticoagulant treatment regimen; the dosages are as recommended by the instructions and the doctor. Peritoneal dialysis for chronic renal failure also does not require treatment adjustment.

The drug dosage regimen changes if the patient requires elective surgery. Since warfarin reduces blood clotting, the risk of bleeding becomes significantly higher, therefore, a week before the planned intervention, the INR is determined, and warfarin is discontinued approximately 2-5 days depending on its level. In case of risk of thrombosis, it is replaced with heparin administered subcutaneously.

During and after surgery, the risk of thrombosis is eliminated by the administration of heparin, which is used in the postoperative period in parallel with the restoration of warfarin under strict control of coagulation.

Warfarin and pregnancy

According to the instructions for use, Warfarin quickly penetrates (almost in pure form) through the placenta and causes a teratogenic effect on the developing fetus. This leads to the development of the so-called warfarin syndrome at approximately 6-12 weeks from the start of pregnancy. Its manifestations include:

• atrophy (partial or complete death) of the optic nerve;
• nasal hypoplasia (deformation of cartilage tissue progressing in the fetus, for example, a saddle-shaped nose);
• inhibition of mental or physical development;
• punctate chondrodysplasia (visible during X-ray examination, develops in the spine and even sometimes in long bones);
• short hands and fingers;
• cataracts with the risk of partial or even complete blindness;
• microcephaly;
• fetal death.

Warfarin causes increased bleeding, which is very dangerous in the prenatal period and directly during childbirth. During lactation, the medicine is excreted along with breast milk, but in extreme cases its use is allowed when prescribed by a doctor. There is no data on the effect of the drug on fertility.

Warfarin has a number of side effects - be careful with dosage

How safe is the drug for children?

Detailed information regarding the use of Warfarin in childhood based on practical studies is not available. But if the result justifies the means, and there are no problems with liver function, then the drug can be prescribed to the child. At the same time, he must receive proper nutrition; the diet is developed individually.

Before use, it is important to correctly calculate the dosage. Initially, it should not exceed the parameters of 0.2 mg/kg body weight. In case of viral lesions and functional disorders of the liver, the dosage is reduced by 2 times. To calculate the amount of the drug during the maintenance period, INR values ​​are used.

Side effects

Depending on the age, build and other characteristics of the human body, the following side effects may be observed after taking the drug:

• blood observed in urine;
• problems with the gastrointestinal tract - diarrhea, prolonged constipation, nausea, dull pain in the stomach;
• allergic reactions - itching and rashes on the skin, anemia, age spots, eosinophilia, jaundice, a rash similar to seasonal allergies, urticaria;
• increased body temperature - the patient must be given an antipyretic drug and immediately consult a doctor;
• bruises under the skin - stop using the drug and immediately consult an experienced doctor;
• tissue necrosis;
• slight hair loss;
• kidney problems - nephritis.

Warfarin

Monitoring

A prerequisite for therapy with Warfarin is the patient's strict adherence to the recommended dose of the drug.

The target INR value for oral anticoagulant therapy to prevent thromboembolic complications in patients with prosthetic heart valves is 2.5-3.0; for other indications - 2.0-3.0.

Patients suffering from alcoholism or dementia may be unable to adhere to the prescribed regimen of Warfarin.

Factors influencing the effect of warfarin

In conditions such as fever, hyperthyroidism, decompensated heart failure, alcoholism with concomitant liver damage, the effect of Warfarin may be enhanced. Increased effects of warfarin, requiring dose reduction, may also occur with weight loss, acute comorbidities, and smoking cessation.

The effect of warfarin may be reduced in hypothyroidism. A decrease in the effect of warfarin, requiring an increase in the dose of the drug, is possible with weight gain, as well as with diarrhea and vomiting.

Patients with a mutation of the gene encoding the CYP2C9 isoenzyme

Patients with a mutation in the gene encoding the CYP2C9 isoenzyme have a longer T1/2 of warfarin. These patients require lower doses of Warfarin, since the risk of bleeding increases when using normal therapeutic doses. If it is necessary to achieve a rapid antithrombotic effect, it is recommended to begin therapy with the administration of heparin; then, for 5-7 days, combination therapy with heparin and warfarin should be carried out until the target INR value is maintained for 2 days (see section "Dosage and Administration").

In the case of rare individual resistance to warfarin (extremely rare), 5-20 loading doses of Warfarin are required to achieve a therapeutic effect.

If the use of Warfarin in such patients is ineffective, other possible reasons should be identified, for example, concomitant use of other drugs (see section “Interaction with other drugs”), inadequate diet, laboratory errors.

Calciphylaxis

Calciphylaxis is a rare syndrome characterized by calcification of blood vessels with skin necrosis and is associated with high mortality. This complication is mainly observed in patients with end-stage renal disease on dialysis, or in patients with known risk factors such as protein C or S deficiency, hyperphosphatemia, hypercalcemia, or hypoalbuminemia. Rare cases of calciphylaxis have been described when taking warfarin in patients who do not have kidney disease. If calciphylaxis develops, appropriate treatment should be initiated and discontinuation of warfarin therapy should be considered.

Thrombophilia

Patients with protein C deficiency are at increased risk of developing skin necrosis when starting warfarin. In patients with protein C deficiency, treatment with warfarin should be initiated without a loading dose, even if heparin is used concomitantly. With protein S deficiency there is also a risk of skin necrosis, so it is advisable for such patients to start warfarin therapy with low doses.

Ischemic stroke

Anticoagulant therapy after ischemic stroke increases the risk of secondary hemorrhage in the necrotic area of ​​the brain. In patients with atrial fibrillation, long-term use of warfarin is beneficial. However, the risk of early recurrence of embolism is low, so temporary cessation of therapy after an ischemic stroke is advisable. Warfarin treatment should be restarted 2 to 14 days after an ischemic stroke, depending on the size of the infarction and blood pressure. In patients with major embolic stroke or uncontrolled hypertension, warfarin should be discontinued for 14 days.

Surgical interventions

Surgeries not associated with the risk of severe bleeding can be performed with an INR < 2.5. If there is a risk of serious bleeding, warfarin should be discontinued 3 days before surgery. If it is necessary to continue anticoagulant therapy (for example, with a high risk of life-threatening thromboembolic complications), the INR should be reduced to <2.5 and heparin therapy should be started (see section "Dosage and Administration").

If surgery is necessary and warfarin cannot be stopped 3 days before surgery, the anticoagulant effect of warfarin should be stopped with low-dose vitamin K supplements.

The timing of resumption of warfarin therapy depends on the risk of postoperative bleeding. In most cases, warfarin can be restarted as soon as the patient can take the tablets by mouth.

Dental procedures

You should not stop taking warfarin before routine dental procedures (for example, before a tooth extraction).

Renal dysfunction

In chronic renal failure or nephrotic syndrome, the concentration of the free fraction of warfarin in the blood plasma increases, which, depending on concomitant diseases, can lead to either an increase or decrease in the effect. In cases of moderate renal failure, the effect of warfarin is enhanced. Caution is recommended when using warfarin in patients with impaired renal function. In all of the above conditions, careful monitoring of INR values ​​should be carried out.

Thyroid diseases

The rate of warfarin metabolism depends on the functional state of the thyroid gland. Therefore, patients with hyper- or hypothyroidism require careful monitoring when initiating warfarin therapy.

Elderly patients

Treatment of elderly patients should be carried out with caution, because the synthesis of blood coagulation factors and hepatic metabolism in such patients is reduced, as a result of which the effect of warfarin may be enhanced.

Diet while using Warfarin

According to recent studies, plants of the cabbage family are very rich in vitamin K. It is its excess that affects INR levels and reduces the effectiveness of Warfarin. But at the same time, if your daily food does not contain vitamin K at all, this can lead to bleeding. This is why a balanced diet and strict adherence to the diet are so important for the entire period of treatment and use of the drug.

It is advisable to exclude all green foods. The greatest amount of vitamin K contains:

• lettuce;
• avocado is a tropical fruit with a large seed, suitable for salads, and has a nutty flavor;
• chayo leaf;
• coriander – the seeds of cilantro, which is very popular in Georgian and Armenian cuisine;
• chicory is a well-known coffee substitute;
• green mustard;
• parsley – very useful for men’s health and potency;
• pistachios - you should not buy salted ones, which are produced as a snack for beer;
• spinach greens - vitamins are contained only in fresh greens, frozen is suitable for consumption in this case;
• soya beans;
• Brussels sprouts;
• turnip greens;
• broccoli and classic cabbage;
• onion;
• cucumbers – the largest amount of vitamin is contained in the peel;
• kiwi is a fragrant and tasty fruit;
• mint - do not overuse, it is a powerful sedative;
• olive oil – can be used for salad dressing and frying;
• amaranth greens;
• young peas;
• red seaweed;
• watercress.

Along with useful products, there are also dangerous ones, such that they can significantly increase the risk of bleeding and even lead to death if they are used simultaneously while using Warfarin. And although the instructions for the drug do not contain such contraindications, it is recommended to refrain from eating the following berries and plants:

• currant;
• anise;
• ginger and garlic;
• echinacea and ginseng;
• cordyceps;
• wort;
• fish fat;
• rose hip;
• lingonberries, strawberries and cranberries;
• dandelions;
• grapefruit;
• gingko biloba and chamomile;
• horse chestnut;
• cherries.

When purchasing a product in a store, do not forget to study the label, which indicates its composition. Particular attention should be paid to searching the list for vitamin K. It is often found in processed foods and carbonated sweet drinks or juices (berry ones are especially dangerous). For example, you can drink no more than 1 glass (200 ml) of cranberry juice per day.

Warfarin nycomed tab 2.5 mg vial plast 100 pcs

It is NOT RECOMMENDED to start or stop taking other medications, or change the dosage of medications taken, without consulting your doctor. When prescribing concomitantly, it is also necessary to take into account the effects of stopping the induction and/or inhibition of the action of warfarin by other drugs. The risk of severe bleeding increases when taking warfarin simultaneously with drugs that affect platelet levels and primary hemostasis: acetylsalicylic acid, clopidogrel, ticlopidine, dipyridamole, most non-steroidal anti-inflammatory drugs (with the exception of cyclooxygenase-2 inhibitors), antibiotics of the penicillin group in high doses. You should also avoid the combined use of warfarin with drugs that have a pronounced inhibitory effect on the cytochrome P450 system, for example, cimetidine and chloramphenicol, when taken for several days the risk of bleeding increases. In such cases, cimetidine can be replaced, for example, with ranitidine or famotidine. Substances that reduce the effect of warfarin:

Cardiovascular drugs: cholesterol - decreased absorption of warfarin and effect on enterohepatic recirculation; bosentan induction of warfarin conversion to CYP2C9/CYP3A4 in the liver

Gastrointestinal drugs: aprepitant - induction of the conversion of warfarin to CYP2C9, mesalazine - the possibility of reducing the anticoagulant effect of warfarin, sucralfate - the possibility of reducing the absorption of warfarin

Dermatological drugs: griseofulfin - reducing the anticoagulant effect of coumarins, retinoids - the possibility of reducing the activity of warfarin.

Anti-infectives: dicloxacillin - increased metabolism of warfarin, rifampicin - increased metabolism of warfarin, joint use of these drugs should be avoided, antiviral agents (nevirapine, ritonavir) - increased metabolism of warfarin mediated by CYP2C9, nafcillin - decreased anticoagulant effect of warfarin.

Medicines for muscle, joint and bone pain: phenazone - induction of enzyme metabolism, reduction in plasma warfarin concentrations, an increase in warfarin dosage may be required; Rofecoxib's mechanism of interaction is unknown.

Drugs affecting the central nervous system: 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; glutethimide - reduction of the anticoagulant effect of warfarin due to increased metabolism; chlordiazepoxide - reducing the anticoagulant effect of warfarin.

Cytostatics: aminoglutethimide - increased metabolism of warfarin; azathioprine - decreased absorption of warfarin and increased metabolism of warfarin; mercaptopurine - reducing the anticoagulant effect of warfarin; mitotane - may reduce the anticoagulant effect of warfarin.

Immunosuppressants: Cyclosporine-warfarin increases the level of cyclosporine or enhances its effect by affecting the metabolism of cyclosporine.

Lipid-lowering agents: cholestyramine may reduce the anticoagulant effect of warfarin due to a decrease in its absorption.

Diuretics: spironolactone, chlorthalidone - taking diuretics in the case of a pronounced hypovolemic effect can lead to an increase in the concentration of clotting factors, which reduces the effect of anticoagulants.

Traditional medicine: St. John's wort (Hypericum perforatum) - enhances the metabolism of warfarin by CYP P450-3A4 and -1A2 (metabolism of R-warfarin), as well as by CYP P450-2C9 (metabolism of Swarfarin). The effect of enzyme induction may persist for 2 weeks after the end of use of St. John's wort. If the patient is taking St. John's wort preparations, the INR should be measured and the 11th dose should be stopped. INR monitoring should be careful because... its level may increase when St. John's wort is discontinued. After this, warfarin can be prescribed; ginseng (Panax ginseng) - likely to induce the conversion of warfarin in the liver. The combined use of these drugs should be avoided.

Foods that may reduce the effects of warfarin: Foods that contain vitamin K. Vitamin K is found most in green vegetables (eg, amaranth, cabbage, avocado, broccoli, Brussels sprouts, canola oil, chayo leaf, onion, coriander (cilantro) , cucumber peel, chicory, kiwi fruit, lettuce, mint, mustard greens, olive oil, parsley, peas, pistachios, red seaweed, spring onions, soybeans, tea leaves (but not tea-drink), turnip greens, watercress, spinach), therefore, when treating with warfarin, these foods should be taken with caution.

Vitamins: vitamin C - reducing the anticoagulant effect of warfarin; Vitamin K-warfarin blocks the synthesis of vitamin K-dependent coagulation factors.

Substances that enhance the effect of warfarin

Drugs affecting the blood and hematopoietic organs: abciximab, tirofiban, eptifibatide, clopidogrel, heparin - additional effect on the blood coagulation system.

Drugs affecting the gastrointestinal tract and metabolism: cimetidine has a pronounced inhibitory effect on the cytochrome P450 system (cimetidine can be replaced with ranitidine or famotidine), leading to a decrease in the metabolism of warfarin; glibenclamide - enhances the anticoagulant effect of warfarin; omeprazole - enhances the anticoagulant effect of warfarin.

Drugs affecting the cardiovascular system: amiodarone - decreased metabolism of warfarin after one week of co-administration. This effect may persist for one to three months after stopping amiodarone; ethacrynic acid - may enhance the effect of warfarin due to the displacement of warfarin from protein bonds; lipid-lowering drugs (fluvastatin, simvastatin, rosuvastatin, gemfibrozil, bezafibrate, clofibrate, lovastatin, fenofibrate) - competition for metabolism mediated by cytochromes P450 2C9 and 3A4; propafenone - decreased metabolism of warfarin; quinidine - decreased synthesis of blood clotting factors; diazoxide - can replace warfarin, bilirubin or other highly protein-bound substance from protein bonds; digoxin - increased anticoagulant effect; propranolol - increased anticoagulant effect; Ticlopidine - increased risk of bleeding. It is necessary to monitor INR levels; dipyridamole - increased levels of warfarin or dipyridamole due to potentiation of effects. Increased risk of bleeding (hemorrhages).

Dermatological agents: miconazole (including in the form of an oral gel) - reducing the intrinsic clearance of warfarin and increasing the free fraction of warfarin in plasma; decreased metabolism of warfarin mediated by cytochrome P450.

Genitourinary system and sex hormones: steroid hormones - anabolic and/or androgenic (danazol, testosterone) Reduced metabolism of warfarin and/or direct effect on the coagulation and fibrinolysis systems.

Hormones for systemic use: agents acting on the thyroid gland - enhancing the metabolism of vitamin K-dependent coagulation factors; glucagon - enhances the anticoagulant effect of warfarin.

Antigout drugs: allopurinol - enhances the anticoagulant effect of warfarin; sulfinpyrazone - increased anticoagulant effect due to a decrease in its metabolism and weakening of bonds with proteins

Anti-infectives: penicillins in large doses (cloxacillin, amoxicillin) - the possibility of increasing the likelihood of bleeding, including bleeding from the gums, nose, unusual bruising or dark stools; tetracyclines - the possibility of enhancing the anticoagulant effect of warfarin; sulfonamides (sulfamethizole, sulfafurazole, sulfafenazole) - the possibility of enhancing the anticoagulant effect of warfarin; quinolones (ciprofloxacin, norfloxacin, ofloxacin, grepafloxacin, nalidixic acid) - decreased metabolism of warfarin; macrolides (azithromycin, clarithromycin, erythromycin, roxithromycin) - decreased metabolism of warfarin; antifungal agents (fluconazole, itraconazole, ketoconazole, metronidazole) - decreased metabolism of warfarin; chloramphenicol - decrease in warfarin metabolism, pronounced inhibitory effect on the cytochrome P450 system; cephalosporins (cefamandole, cephalexin, cefmenoxime, cefmetazole, cefoperazone, cefuroxime) - enhancing the effect of warfarin due to suppression of the synthesis of vitamin K-dependent blood coagulation factors and other mechanisms; sulfamethoxazole-trimethoprim-reduces the metabolism of warfarin and displaces warfarin from protein binding sites.

Anthelmintics: levamisole—enhanced anticoagulant effect of warfarin

Centrally acting antitussives: Codeine—a combination of codeine and paracetamol enhances the activity of warfarin.

Remedies for muscle, joint and bone pain: acetylsalicylic acid - displaces warfarin from plasma albumin, restricts the metabolism of warfarin; NSAIDs - azapropazone, indomethacin, oxyphenbutazone, piroxicam, sulindac, tolmetin, feprazone, celecoxib, etc. (with the exception of cyclooxygenase-2 inhibitors) - competition for metabolism carried out by cytochrome P450 2C9 enzymes; leflunomide - restriction of warfarin metabolism mediated by CYP2C9; paracetamol (acetaminophen) (especially after 1 - 2 weeks of continuous use) - limiting the metabolism of warfarin or influencing the formation of coagulation factors (this effect does not occur when taking less than 2 g of paracetamol per day); phenylbutazone - decreases the metabolism of warfarin, displaces warfarin from protein binding sites. This combination should be avoided; narcotic analgesics (dextropropoxyphene) - enhancing the anticoagulant effect of warfarin.

Drugs affecting the central nervous system: antiepileptic drugs (fosphenytoin, phenytoin) - displacement of warfarin from protein binding sites, increased metabolism of warfarin; tramadol competition for cytochrome P450 3A4-mediated metabolism; antidepressants: selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, sertraline) - limitation of warfarin metabolism. SSRIs are believed to limit the cytochrome P450 2C9 isoenzyme (CYP2C9). It is the enzyme that metabolizes the most potent isomer, Swarfarin. In addition, both SSRIs and warfarin bind strongly to albumin. In the presence of both, the possibility of displacing one of the compounds from albumin increases; chloral hydrate-mechanism of interaction is unknown.

Cytostatics: fluorouracil - reduction in the synthesis of cytochrome P450 2C9 enzymes that metabolize warfarin; capecitabine - reduction of CYP2C9 isoenzymes; imatinib competitive inhibition of the CYP3A4 isoenzyme and suppression of warfarin metabolism mediated by 16 CYP2C9 and CYP2D6; ifosfamide - suppression of CYP3A4; Tamoxifen Tamoxifen, a CYP2C9 inhibitor, may increase serum concentrations of warfarin due to decreased metabolism; methotrexate - increased effect of warfarin due to decreased synthesis of proagulant factors in the liver; tegafur - enhances the anticoagulant effect of warfarin; trastuzumab - enhancing the anticoagulant effect of warfarin; flutamide - enhances the anticoagulant effect of warfarin; cyclophosphamide - The likelihood of changing the anticoagulant effect of warfarin, because cyclophosphamide is an antitumor agent.

Cytotoxic drugs: etoposide may enhance the anticoagulant effect of coumarins.

Immunomodulators: alpha and beta interferon - an increase in the anticoagulant effect and an increase in the concentration of warfarin in serum necessitates a reduction in the dosage of warfarin.

Drugs for the treatment of addiction: disulfiram - reduction in the metabolism of warfarin.

Diuretics: metolazone - enhances the anticoagulant effect of warfarin; Thienylic acid - enhances the anticoagulant effect of warfarin.

Drugs for the treatment of bronchial asthma: zafirlukast - increased levels or increased effect of zafirlukast while taking warfarin due to changes in the metabolism of zafirlukast.

Antihyperglycemic drugs: troglitazone - decreased levels or weakened effect of warfarin due to changes in the metabolism of warfarin.

Vaccines - influenza vaccine - the ability to enhance the anticoagulant effect of warfarin.

Antimalarials: Proguanil may enhance the anticoagulant effect of warfarin in anecdotal reports.

Food: Cranberry-cranberry reduces CYP2C9-mediated metabolism of warfarin, tonic drinks containing quinine - consumption of large quantities of tonic drinks containing quinine may result in the need to reduce the dosage of warfarin. This interaction can be explained by a decrease in the synthesis of proagulant factors in the liver by quinine, ginkgo (Ginkgo biloba), garlic (Allium sativum), angelica sinensis, papaya (Carica papaya), sage (Salvia miltiorrhiza) - potentiation of the anticoagulant / antiplatelet effect may increase the risk of bleeding.

Substances that reduce or enhance the effect of warfarin

Drugs affecting the cardiovascular system - disopyramide - may weaken or enhance the anticoagulant effect of warfarin

Dietary Supplements: CoQ10 Coenzyme Q10 may enhance or inhibit the effects of warfarin due to the homogeneous chemical structure between CoQ10 and vitamin K.

Other substances: alcohol (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 carry out monitoring (INR) at the beginning and end of treatment, and, if possible, after 2-3 weeks from the start of therapy.

Interaction with other medications

What indications Warfarin has can be read in more detail in the instructions itself, but before that you need to thoroughly understand whether it interacts with other medications. For convenience, we offer sorting of medications that can become active and conflict with Warfarin into groups:

1. Antibiotics of general and targeted action - Ciprofloxacin (Ciproxin), it is very dangerous to use Erythromycin, Metronidazole (Flagyl) during this period; Sulfamethoxazole with Trimethoprim (Bactrim) is rarely prescribed.
2. Medicines whose action is aimed at normalizing heart function and reducing the level of bad cholesterol - Aspirin, Clopidogrel (Plavix), Amiodarone (Cordarone), the most popular in Europe are Simvastatin (Zukor) and its analog Fenofibrate.
3. Antidepressants - Fluoxetine (Prozac), Fluvoxamine (Fevarin), Paroxetine has a calming effect.
4. Hormones similar to those secreted by the thyroid gland, the most common is Thyroxine.
5. Antiviral and antipyretic drugs – Paracetamol.
6. Anti-inflammatory (including colds) and painkillers (especially those used to treat arthritis) - most often prescribed are Aspirin, Meloxicam (Mobis) or their analogue Celecoxib; pharmacies usually recommend Ibuprofen (Nurofen), Indomethacin (Indocid), Methyl salicylate (Deep Hit Ointment) or the most budget option - Paracetamol (Panadol).
7. Antiulcer drugs - Esomeprazole (Nexium), especially dangerous Cimetidine (Tagamet), Omeprazole.
8. Corticosteroids – Prednisolone.
9. Antiepileptic drugs – Carbamazepine (Tegretol).
10. Antifungal drugs - Miconazole (Daktarin), analogues can be considered Fluconazole (Diflucan), Griseofulvin.

In what cases is the drug discontinued?

It is strictly prohibited to stop using Warfarin or change the prescribed dosage on your own! In most cases, it will need to be used for life, but sometimes discontinuation occurs due to improvement in the condition and INR values. If you suddenly stop using Warfarin, this can lead to blood clots and increase the risk of death due to internal bleeding.

Early use of the drug according to the instructions may be canceled in the following cases:

• allergic reaction to the active substance;
• complications after using Warfarin;
• the need for surgery;
• in case of poisoning and overdose.

The daily dose of Warfarin is calculated individually and is usually in the range of 2.5-7.5 mg of the substance. Imported analogues are practically no different in effectiveness from domestic ones, but alternating their use is prohibited.

Warfarin: use, rules of administration, selection of dosages.

The content of the article:

1. General information about taking warfarin.
2. Contraindications.
3. INR control. Target INR range.
4. INR value for patients with prosthetic heart valves.
5. About a missed dose or temporary discontinuation of the drug.
6. Selection of warfarin dosages and rules for changing the dose of drugs.
7. Diet while taking warfarin.
8. Precautionary measures.
9. Interaction of warfarin with other drugs.
10. Portable devices for self-monitoring of INR at home.

General information about taking warfarin.

Warfarin is a drug (anticoagulant) that reduces blood clotting. It is prescribed when there is a high risk of unwanted blood clots. The most common indications for prescribing warfarin: artificial heart valve, atrial fibrillation, deep vein thrombosis, pulmonary embolism, sometimes after a heart attack, stroke, for thrombophilia (a disease in which blood clotting is increased and blood clots constantly appear).

Warfarin blocks part of vitamin K, from which the liver synthesizes prothrombin, a substance necessary for the formation of blood clots. Vitamin K enters the body with food from green vegetables, and is also produced by human intestinal bacteria. Warfarin “neutralizes” part of vitamin K, and the liver does not receive enough “building material” to create prothrombin. However, warfarin does not dissolve already formed blood clots.

The main condition for taking the drug is that warfarin should be taken every day, without skipping. To take the drug, it is important to determine the time when taking the medicine will be most convenient for you. It is advisable to do this always at the same time and on an empty stomach (food affects the absorption of warfarin, so it is better not to combine them). It is best to take warfarin once a day in the evening.

The length of time you take warfarin depends on the reason you are prescribed warfarin. For example, after installation of an artificial mechanical heart valve or for thrombophilia, taking the drug is indicated for life. After certain other heart surgeries or deep vein thrombosis, warfarin is usually prescribed for 6-12 months.

It is very important to control blood clotting when taking warfarin. The main indicator is the international normalized ratio (INR). The higher the INR value, the thinner the blood. Conversely, the lower the INR value, the thicker the blood. When adjusting the dosage of warfarin, it is important to balance the risk of thrombosis with the risk of bleeding.

Contraindications.

Before taking medications, you need to take into account the contraindications that are indicated in the instructions for the drug:

• manifestation of high sensitivity to the components of the product or suspicion of hypersensitivity;
• acute bleeding;
• severe liver and kidney diseases;
• the first trimester of pregnancy and the last 4 weeks of gestation;
• acute DIC syndrome;
• thrombocytopenia;
• lack of proteins C and S;
• varicose veins of the digestive tract;
• arterial aneurysm;
• increased risk of bleeding, including hemorrhagic disorders;
• stomach and duodenal ulcers;
• severe wounds, including post-operative wounds;
• lumbar puncture;
• bacterial endocarditis;
• hypertension is malignant;
• intracranial hemorrhage;
• hemorrhagic stroke.

Monitoring INR when taking warfarin.

At the stage of selecting the dose of warfarin, INR should be monitored every 3 days, after reaching the target range - once every 5-7 days, after receiving three consecutive results of a blood test for coagulation in the target range, you can switch to measurement once every 2 weeks. In general, it is necessary to measure the INR at least once a month throughout the duration of taking the drug. The best results of treatment with warfarin are achieved by monitoring the blood test for INR once a week. It is also necessary to carry out an INR analysis in case of changing the dose of warfarin, changing diet, taking other medications and other situations that could affect blood clotting. Remember that the INR may not change until 3-7 days after such changes occur.

The normal blood INR of a healthy person not taking Warfarin is about 1 (0.8–1.2). With a decrease in coagulability, the INR increases. The goal of prescribing warfarin is to reduce blood clotting to a level where the risk of thrombosis is significantly reduced, but the risk of bleeding is not yet too high.

For different conditions, this balance point is between certain INR numbers; Thus, when performing a blood test for INR, normal is a relative concept. For example, when installing a mechanical prosthetic heart valve, it is recommended to increase the INR to 2.5-3.5, and for atrial fibrillation to 2.0-3.0. These numbers are called the target INR range, which varies from patient to patient and depends on what specific disease is causing you to be prescribed Warfarin.

INR value for patients with prosthetic heart valves.

Table 1. Recommended INR value for mechanical heart valves*

Table 2. Recommended INR value for biological heart valves*

Risk factors for TE complications (thromboembolic) include:

• atrial fibrillation;
• history of thrombosis, thromboembolism;
• left ventricular dysfunction (LVD)
• hypercoagulable state. Hypercoagulation - increased blood clotting, predisposing to the formation of blood clots, occurs with malignant neoplasms, blood diseases, and taking oral contraceptives.

About a missed dose or temporary discontinuation of the drug (when switching to a direct anticoagulant).

If you forget to take a warfarin tablet at the usual time, take the missed dose as soon as you remember. However, if it is already time for your next dose, skip the forgotten dose and continue taking the drug according to your regular schedule. Do not take a double dose to make up for a missed dose. Use a warfarin diary. Write down the missed dose in your diary and tell your doctor at your next visit.

If you forget to take warfarin for two or more days, call your doctor immediately!

There are situations when the attending physician recommends that you reduce the daily dose of warfarin or discontinue it for a short time and switch to a direct anticoagulant - heparin. This can include any medical procedure that carries a high risk of bleeding, such as dental, gynecological, urological procedures or minor surgery and cardiac catheterization. In these cases, 1-2 days before invasive interventions, the daily dose of warfarin should be reduced under the control of the INR (reduction of the INR to a level of 2.0). For abdominal surgical interventions, it is necessary to discontinue warfarin and switch to heparin therapy. Heparin therapy is started when the INR decreases to less than 2.0.

The duration of the break in taking warfarin is determined by the specific clinical situation: in the absence of signs of postoperative bleeding (6–12 hours), warfarin should be re-prescribed and heparin should be discontinued when the INR reaches 2.0 or more.

Selection of warfarin dosages and rules for changing the dose of the drug (using the example of 2.5 mg tablets).

Changing the dosage of warfarin (using the example of 2.5 mg tablets).

With a slight increase in INR, for example, with the aortic valve to 4.0 (should be 2.0-3.0) or mitral to 5.0 (should be 2.5-3.5), it is necessary to reduce the daily dose of warfarin by ¼ of that dose which you accept.

If the INR value increases and the aortic valve is about 4.0-4.5 or the mitral valve is about 5.0-5.5, it is necessary to reduce the daily dose of warfarin by ½ of the dose you are taking.

At high INR values ​​(more than 5.0-6.0), skip warfarin for one or more days; after reaching the proper INR value, resume taking warfarin from half the dose at which the previously high INR value was recorded.

The “One Quarter” rule can be used when selecting the dose of warfarin, when changing concomitant therapy, or when overusing foods with a high content of vitamin K.

Warfarin is a drug characterized by individual differences in drug response due to a number of factors.

Factors influencing the effectiveness of warfarin

Diet while taking warfarin

Warfarin acts on blood clotting through vitamin K, which is found in varying amounts in foods (such as green leafy vegetables and herbs).

While taking warfarin you should not:

• allow significant changes in diet (for example, depending on the season);
• change your usual diet without prior approval from your doctor;
• enter into an intensive weight loss program;
• add new vitamins or dietary supplements to your diet without prior approval from your doctor. If you need to take vitamins, it is better to choose multivitamin preparations without vitamin K in the composition.

If you significantly increase your intake of foods rich in vitamin K while on a stable dose of warfarin, this can greatly weaken its effect and lead to blood clots!

Daily requirement of vitamin K: 0.03-1.5 mcg/kg/day (up to 105 mcg/day).

The maximum amount of vitamin K (3000-6000 mcg/kg) is found in dark green leafy vegetables and herbs (spinach, parsley, green cabbage), and in green tea up to 7000 mcg/kg. Intermediate amounts (1000-2000 mcg/kg) - in plants with paler leaves (white cabbage and Brussels sprouts, broccoli, lettuce). Vitamin K is found in legumes and mayonnaise (due to vegetable oils). Fats and oils contain varying amounts of vitamin K (300-1000 mcg/kg), more of it in soybean, rapeseed, and olive oils. The vitamin K content in dairy, meat, bakery products, mushrooms, fruits and many vegetables, black tea, and coffee is low (no more than 100 mcg/kg). Taking multivitamins that contain vitamin K may reduce the effect of warfarin. Regular consumption of berries and cranberry juice may increase the effect of warfarin.

Table. Vitamin K content in foods (µg/100 g)

Warfarin and food There is no need to avoid foods high in vitamin K. You should eat a nutritious diet. Continue to eat what you have always eaten - without making any sudden major changes to your usual diet. It is best to try to adhere to the principles of healthy eating (click on the blue link to learn more about healthy eating). Tell your doctor if you have digestive problems for more than 1 day (nausea, vomiting, bowel movements). Any disease accompanied by diarrhea can lead to vitamin K deficiency and increase the blood-thinning effect.

Some medicinal herbs can both enhance the effect of warfarin, for example: ginkgo biloba, garlic, angelica, papaya, sage, and reduce its effect, for example: ginseng, St. John's wort. In this case, the increased effect of warfarin when taken simultaneously with St. John's wort can persist for two weeks after discontinuation. Monitoring of MHO in these cases must be careful, because its value may increase even more when St. John's wort is discontinued.

Quinine contained in tonic drinks can enhance the effect of warfarin. You should be aware that warfarin can enhance the effect of drugs prescribed for diabetes, which can cause dizziness and weakness. In such cases, you should eat a piece of sugar.

Precautions during treatment with warfarin.

Both deficiency and excess of warfarin are dangerous to life and health. Strictly observe the intervals of control blood tests. Follow your doctor's instructions. With an overdose of warfarin , pinpoint hemorrhages and bruises on the body, bleeding gums, black stools, dark (red) urine, and changes in the menstrual cycle in women are possible.

In cases where the INR increases to 5.0, it is necessary to reduce the daily dose of warfarin or skip 1-2 doses of warfarin if the INR value is from 5.0 to 9.0. However, if you are in doubt about what to do if the INR value increases, then it is better to consult a doctor!

Treatment with warfarin limits the body's natural ability to stop bleeding. For this reason, you should be especially careful with activities that may cause cuts, bleeding, or other injuries. Any head injury can lead to very serious consequences.

Remember!

Independent withdrawal of warfarin is unacceptable, since there is a high probability of thrombotic (thrombosis of a prosthetic heart valve) and thromboembolic (stroke, heart attack, pulmonary embolism) complications!

Discuss any problems that arise with your doctor.

Interaction of warfarin with other drugs

Some antibiotics and cardiac drugs enhance the effect of warfarin, in particular amiodarone (cordarone), acetylsalicylic acid (aspirin) and others. Its effect is reduced by phenobarbital (part of Corvalol), carbamazepine, cytostatics, antacids, diuretics, vitamin C. More details in the table. Drugs that affect the effectiveness of warfarin

• All drugs that you will take together with warfarin must be agreed with your doctor!
• Always disclose that you are taking warfarin when new medications are prescribed to you!

Portable devices for self-monitoring of INR at home.

Currently, there are portable devices for self-determination of INR (similar to systems for monitoring blood sugar levels in patients with diabetes), which can help you keep anticoagulation therapy under control. Among them, CoaguChek® XS has proven itself for patient self-testing and immediate receipt of PTT/INR results. CoaguChek XS provides accurate and reliable results in less than a minute using only 8 µL (one drop of blood). Your doctor will decide what dose of warfarin, test regimen, and monitoring method is best for you.

A portable INR self-monitoring device takes measurements automatically. Built-in internal quality control does not require instrument calibration or use of control solutions. To carry out the analysis, just one drop of blood from a finger applied to the test strip is required, and within a minute the result automatically appears on the device screen.

Benefits of INR self-monitoring

• Improving the effectiveness of INR control through regular monitoring.
• Improved treatment safety through more frequent testing.
• Increasing time within the target range and thereby ensuring higher long-term survival.
• Simplifying the choice of the most effective option for the prevention of thromboembolic complications.
• Increased reliability with immediate, accurate results.
• More independence with the ability to monitor your INR values ​​anywhere, anytime.
• Improved quality of life by reducing the need for medical consultations and travel costs.

Compared with conventional methods, self-testing and self-monitoring can significantly reduce the risk of complications and death. Patients who self-test have a 39% reduction in risk of death and a 90% reduction in risk of complications compared with patients using conventional laboratory monitoring methods. Self-monitoring can reduce the risk of death even further - by 63% compared to conventional methods.

Staying within the therapeutic range longer is the key to treatment success.