Warfarin Nycomed
Warfarin Nycomed: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Warfarin Nycomed
ATX code: B01AA03
Active ingredient: warfarin (Warfarin)
Manufacturer: Takeda Pharma Sp. z.o.o. (Takeda Pharma, Sp.zoo) (Poland)
Description and photo update: 2019-11-07
Prices in pharmacies: from 90 rubles.
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Warfarin Nycomed is an indirect anticoagulant for oral administration.
Release form and composition
Dosage form - tablets: light blue, round biconvex, with a cross-shaped line (50 or 100 tablets in plastic bottles, placed in a cardboard box or without it. The cardboard box also contains instructions for the use of Warfarin Nycomed).
Composition of 1 tablet:
- active substance: sodium warfarin - 2.5 mg;
- auxiliary components: povidone 30 - 1 mg; lactose - 50 mg; corn starch - 34.6 mg; indigo carmine - 0.006 4 mg; calcium hydrogen phosphate dihydrate - 32.2 mg; magnesium stearate - 0.6 mg.
Pharmacological properties
Pharmacodynamics
Warfarin sodium - the active substance of Warfarin Nycomed, is an indirect anticoagulant. Its effect is aimed at blocking the biosynthesis of vitamin K-dependent blood coagulation factors in the liver, namely II, VII, IX and X. As a result, the concentration of these components in the blood decreases and, as a result, the blood coagulation process slows down.
The onset of the anticoagulant effect of warfarin sodium is observed after 36–72 hours, the maximum effect is observed after 5–7 days of daily use of Warfarin Nycomed. The activity of vitamin K-dependent blood coagulation factors is restored 4–5 days after discontinuation of therapy.
Pharmacokinetics
Warfarin sodium is rapidly absorbed from the gastrointestinal tract. Binds to blood plasma proteins at the level of 97-99%.
Metabolism occurs in the liver. Warfarin is a racemic mixture, while the metabolism of the R- and S-isomers (right- and levogyrate, respectively) is carried out in different ways. Both isomers are converted to two main metabolites. For the R-enantiomer of warfarin, the main catalysts of metabolism are the enzymes CYP1A2 and CYP3A4, for the S-enantiomer - CYP2C9. The S-enantiomer, in comparison with the R-enantiomer, has a greater anticoagulant activity (approximately 2-5 times), but the T 1/2 (half-life) of the latter is longer. Patients with polymorphisms of the CYP2C9 enzyme, including the CYP2C9 * 2 and CYP2C9 * 3 alleles, may have an increased sensitivity to warfarin, as well as an increased risk of bleeding.
The excretion of warfarin is carried out with bile in the form of inactive metabolites, which are reabsorbed in the gastrointestinal tract and excreted in the urine. T 1/2 is in the range of 20-60 hours (S-enantiomer - 21-43 hours, R-enantiomer - 37-89 hours).
Indications for use
- thrombosis and embolism of blood vessels: acute / recurrent venous thrombosis, pulmonary embolism (treatment and prevention);
- myocardial infarction (secondary prevention);
- thromboembolic complications after myocardial infarction (prevention);
- thromboembolic complications against the background of atrial fibrillation, lesions of the heart valves, as well as use in patients with prosthetic heart valves (prevention);
- transient ischemic attacks and strokes (treatment and prevention);
- postoperative thrombosis (prevention).
Contraindications
- severe liver and kidney disease;
- acute bleeding;
- acute disseminated intravascular coagulation syndrome;
- thrombocytopenia;
- deficiency of proteins C and S;
- presence of a high risk of bleeding, including bacterial endocarditis, hemorrhagic disorders, esophageal varicose veins, malignant arterial hypertension, intracranial hemorrhage, hemorrhagic stroke, arterial aneurysm, gastric ulcer and duodenal ulcer, lumbar puncture, severe) wounds (including;
- I trimester and the last 4 weeks of pregnancy;
- individual intolerance to the components of Warfarin Nycomed.
Warfarin Nycomed, instructions for use: method and dosage
Warfarin Nycomed is intended for oral administration. The drug should be taken at the same time 1 time per day. The duration of the course is determined individually, depending on the clinical condition of the patient. Treatment can be canceled without gradual dose reduction.
Before starting treatment, the MHO (International Normalized Ratio) is determined. Then laboratory control is carried out regularly 1 time in 4-8 weeks.
If warfarin has not been previously used, the initial daily dose used for 4 days is 5 mg. On the fifth day of treatment, it is necessary to determine the MHO and, based on its value, select a maintenance dose. It is usually in the range of 2.5 to 7.5 mg.
The recommended starting dose for patients who have used warfarin in the past is twice the dose of the known maintenance dose of Warfarin Nycomed and is taken for the first two days. From the third day, treatment is continued at a known maintenance dose. On the fifth day of therapy, the MHO is monitored, after which the dosage regimen may need to be adjusted.
In the treatment and prevention of pulmonary artery embolism, venous thrombosis, atrial fibrillation, dilated cardiomyopathy, complicated heart valve diseases, when prosthetic heart valves with bioprostheses, it is recommended to maintain the MHO index from 2 to 3. Higher MHO values (2.5–3.5) are recommended with complicated acute myocardial infarction and prosthetics of heart valves with mechanical prostheses.
In children, information on the use of warfarin is limited. The decision to prescribe the drug should be made by an experienced professional. Typically, the initial daily dose is 0.1 or 0.2 mg / kg with impaired liver function and their absence, respectively. The maintenance dose is adjusted according to the MHO value. The recommended MHO levels in children are the same as in adults. The therapy is carried out under medical supervision.
On the first day, children with an INR of 1–1.3 are assigned a loading dose of Warfarin Nycomed 0.2 mg / kg. Then, over three days, the dose is determined by the INR value (in% of the loading dose):
- INR 1-1.3: 100%;
- INR 1.4–3: 50%;
- INR 3.1-3.5: 25%.
If the value of the indicator is> 3.5, you must stop taking Warfarin Nycomed. After an INR <3.5 is reached, treatment is resumed at a dose equal to 50% of the previous one.
Maintenance therapy (weekly dose), depending on the INR value:
- INR 1–1.3: increase the dose by 20% of the loading dose;
- INR 1.4–1.9: increase the dose by 10% of the loading dose;
- INR 2–3: no dose adjustment required;
- INR 3.1-3.5: reduce the dose by 10% of the loading dose.
If the value of the indicator is> 3.5, you must stop taking Warfarin Nycomed. After reaching an INR <3.5, treatment is resumed at a dose of 20% of the previous one.
Elderly patients have a higher risk of developing adverse events, which requires careful medical supervision.
Patients with impaired liver function should be carefully monitored for MHO values, since this group of patients has an increased sensitivity to warfarin.
In case of impaired renal function, the use of Warfarin Nycomed in a reduced dose is indicated under close control of the condition.
The MHO must be determined a week before the planned (elective) surgery. You should stop taking Warfarin Nycomed a few days before surgery (determined by the MHO indications):
- MHO> 4: in 5 days;
- MHO 3-4: in 3 days;
- INR 2-3: in 2 days.
In the evening before the operation, it is necessary to determine the MHO, if the INR is> 1.8, vitamin K 1 is administered intravenously or orally at a dose of 0.5–1 mg.
In the presence of a high risk of thrombosis, low molecular weight heparin is injected subcutaneously for prophylaxis. After the operation, therapy is continued for 5-7 days along with concomitant reinstated warfarin.
After small operations, the administration of warfarin is continued with the usual maintenance dose on the same day in the evening, after large operations - on the day when the patient begins to receive enteral nutrition.
Side effects
Against the background of the use of Warfarin Nycomed, the following adverse events may develop (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rarely):
- hematopoietic system: very often - bleeding (in different organs); often (after prolonged therapy) - hypersensitivity to warfarin;
- skin and subcutaneous tissues: rarely - itching, skin necrosis, vasculitis, alopecia, urticaria, rash; very rarely - coumarin necrosis, palmar-plantar syndrome;
- digestive system: often - nausea, vomiting, diarrhea; very rarely - melena;
- cardiovascular system: rarely - purple finger syndrome; very rarely - cholesterol embolism;
- liver: rarely - jaundice, increased activity of liver enzymes;
- others: often - hypersensitivity reactions (manifested as a skin rash and characterized by cholestatic hepatitis, priapism, vasculitis, a reversible increase in the concentration of liver enzymes, tracheal calcification and reversible alopecia).
Among patients receiving warfarin, bleeding during the year is observed in approximately 8% of cases, while of them as severe (retroperitoneal, intracranial), in which a blood transfusion or hospitalization is required, 1% are classified as fatal - 0.25%. The most common risk factor for the development of intracranial hemorrhage is considered uncontrolled / untreated arterial hypertension. If the MHO is significantly exceeded, the risk of bleeding increases. In cases where bleeding begins with MHO, the value of which is within the target level, other associated conditions should be investigated.
Examples of such complications are hemoptysis, bleeding from the gums, nose and subconjunctival bleeding, hematuria, vaginal bleeding, bruising on the skin, bleeding from the rectum and other parts of the gastrointestinal tract, intracerebral bleeding, heavy or prolonged bleeding after surgery or injury. You can expect bleeding in any organ, including severe. There is evidence of bleeding in patients receiving long-term treatment with anticoagulants, which led to hospitalization, the need for blood transfusion or death.
Independent risk factors for significant bleeding during therapy with Warfarin Nycomed: aggravated history of stroke, gastrointestinal bleeding, high level of anticoagulation, atrial fibrillation, concomitant diseases, old age. Patients with CYP2C9 polymorphism may have an increased risk of excessive anticoagulant exposure and bleeding episodes. Such patients should be closely monitored for INR and hemoglobin levels.
Coumarin necrosis is a rare complication of warfarin therapy. Usually, necrosis begins with darkening and swelling of the skin of the buttocks and lower extremities, or (more rarely) elsewhere. Then the lesions become necrotic. In most cases (90%) this disorder occurs in women and is associated with a deficiency of antithrombotic protein C or S. The lesions occur within 3-10 days of taking Warfarin Nycomed. In congenital deficiencies of these proteins, warfarin should be started with low initial doses of the drug in combination with the introduction of heparin. If a complication occurs, warfarin is discontinued and heparin is continued until the lesions heal or scar.
Palmar-plantar syndrome is one of the very rare complications of warfarin, the development of this disorder is typical for men with atherosclerotic diseases. Warfarin presumably causes hemorrhages in atheromatous plaques, leading to microembolism. Symmetrical purple lesions of the skin of the soles and toes may occur, accompanied by burning pains.
After discontinuation of Warfarin Nycomed, these symptoms from the skin gradually disappear.
Overdose
The main symptoms: minor bleeding, including microhematuria, bleeding of the gums (since the indicator of the effectiveness of therapy is at the border of the development of bleeding).
Therapy: in mild cases, a reduction in the dose of Warfarin Nycomed or a short-term discontinuation of treatment is sufficient. In patients with minor bleeding, therapy is stopped until the MHO reaches the target level. For severe bleeding, oral administration of activated charcoal, intravenous administration of vitamin K, fresh frozen plasma or clotting factor concentrate is recommended.
Patients who are subsequently indicated for the appointment of oral anticoagulants should avoid large doses of vitamin K, since resistance to warfarin develops within 14 days.
Treatment regimen for minor bleeding (depending on the INR level):
- INR <5: the dose of warfarin should be skipped; when the therapeutic level of INR is reached, therapy is continued with lower doses;
- INR 5-9: taking 1–2 doses of warfarin should be skipped; when the therapeutic level of INR is reached, therapy is continued with lower doses. An alternative is to skip 1 dose of warfarin and administer vitamin K 1–2.5 mg orally;
- INR> 9: taking Warfarin Nycomed is canceled, 3-5 mg of vitamin K is prescribed orally.
Cancellation of the drug is indicated in the following cases (depending on the INR level):
- INR 5-9 - surgery is planned: taking Warfarin Nycomed is stopped and vitamin K is prescribed orally at a dose of 2-4 mg (24 hours before the planned operation);
- INR> 20 or severe bleeding: Give 10 mg vitamin K by slow intravenous infusion, transfusion of prothrombin complex factor concentrates, whole blood, or fresh frozen plasma. If necessary, vitamin K is re-administered every 12 hours.
T 1/2 of warfarin is 20-60 hours, therefore, after therapy, long-term monitoring of the patient's condition is required.
special instructions
Strict adherence to patients receiving the prescribed dose of Warfarin Nycomed is a prerequisite for therapy. Some patients (eg, those with dementia, alcoholism) may not be able to adhere to the prescribed dosage regimen.
Hyperthyroidism, alcoholism with concomitant liver damage, fever, decompensated heart failure can enhance the effect of warfarin. In hypothyroid patients, the effect of warfarin may be reduced.
With nephrotic syndrome or renal failure, the plasma level of the free fraction of warfarin in the blood increases, which, depending on concomitant diseases, can both enhance and reduce the effect. In patients with moderate hepatic impairment, an increase in the effect of Warfarin Nycomed is observed. In the presence of any of the above conditions, the MHO value must be carefully monitored.
During the period of therapy, it is recommended to take paracetamol, opiates or tramadol as pain relievers.
Patients with a mutation in the gene encoding the CYP2C9 enzyme have a longer T 1/2 of warfarin. In such cases, to reduce the risk of bleeding, Warfarin Nycomed is used in reduced doses.
Warfarin Nycomed contains lactose, therefore, with rare hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, the drug should not be used.
If a rapid antithrombotic effect is required, it is recommended to start treatment with heparin. Then, for 5–7 days, a combination therapy with heparin and warfarin is carried out until the target MHO value is reached and maintained for 2 days.
If protein C is insufficient, there is a possibility of developing skin necrosis without the use of a shock dose of warfarin. In this case, treatment should be started without a loading dose of warfarin, even with heparin. In patients with protein S deficiency, this risk may also be present, and therefore a slower initiation of the use of Warfarin Nycomed is recommended.
In patients with individual resistance to warfarin (occurs in rare cases), 5–20 loading doses of warfarin may be required to achieve a therapeutic effect. If therapy is ineffective, other possible causes should be considered, including laboratory errors, inadequate diet, combined use with other drugs.
In elderly patients, a decrease in the synthesis of coagulation factors and hepatic metabolism must be taken into account, due to which an excessive effect from the action of warfarin is possible.
In case of impaired renal function in patients at risk of hypercoagulability (against the background of severe arterial hypertension or kidney disease), more frequent monitoring of the INR level is indicated.
Application during pregnancy and lactation
Warfarin Nycomed 2.5 mg tablets should not be used in the first trimester and during the last 4 weeks of pregnancy. In the remaining periods, except in cases of urgent need, the use of warfarin is not recommended.
Taking Warfarin Nycomed during pregnancy can lead to congenital malformations and fetal death. Warfarin quickly penetrates the placental barrier, exerting a teratogenic effect on the fetus and leading to warfarin syndrome in the fetus at 6–12 weeks of gestation. The syndrome manifests itself in the form of microcephaly, nasal hypoplasia (saddle deformity of the nose and other cartilage changes) and point chondrodysplasia on X-ray examination (especially in the long bones and spine), short hands and fingers, delayed physical and mental development, atrophy of the optic nerve, cataracts leading to complete blindness. At the end of pregnancy and during labor, Warfarin Nycomed can cause bleeding.
Women of reproductive age should use effective methods of contraception during therapy.
Warfarin is excreted in breast milk, however, in the case of taking Warfarin Nycomed in therapeutic doses, the effect on a nursing child is not expected.
There is no data on the effect of warfarin on fertility.
With impaired renal function
In severe kidney disease, the appointment of Warfarin Nycomed is contraindicated.
For violations of liver function
In severe liver diseases, the appointment of Warfarin Nycomed is contraindicated.
Drug interactions
It is not recommended to start / stop taking other medications or change doses without consulting a doctor.
When prescribing combination therapy, the effects of stopping the induction / inhibition of the action of warfarin by other drugs should also be taken into account.
The likelihood of severe bleeding increases with the combined use of warfarin with drugs that affect primary hemostasis and platelet levels, including acetylsalicylic acid, ticlopidine, clopidogrel, dipyridamole, antibiotics of the penicillin group (if used in large doses), most non-steroidal anti-inflammatory drugs (except for anti-inflammatory drugs) COG-2).
It is also necessary to avoid the combined appointment of Warfarin Nycomed with agents that have a pronounced inhibitory effect on isozymes of the cytochrome P 450 system (cimetidine, chloramphenicol), since against the background of their use for several days, the risk of bleeding increases. In such cases, cimetidine can be replaced with another drug, for example, ranitidine or famotidine.
Drugs, when combined with which the effect of warfarin decreases:
- bosentan: induces the transformation of warfarin to CYP2C9 / CYP3A4 in the liver;
- cholestyramine: reduces the absorption of warfarin (due to which the anticoagulant effect of warfarin may decrease) and affects enterohepatic recirculation;
- mesalazine: may reduce the anticoagulant effect of warfarin;
- aprepitant: induces the transformation of warfarin to CYP2C9;
- griseofulvin: the anticoagulant effect of coumarins decreases;
- sucralfate: there is a risk of reduced absorption of warfarin;
- dicloxacillin, aminoglutethimide: warfarin metabolism increases;
- mitotane: the anticoagulant effect of warfarin may be reduced;
- retinoids: there is a risk of decreased activity of warfarin;
- antiviral agents (nevirapine, ritonavir): warfarin metabolism mediated by CYP2C9 is enhanced;
- phenazone: induction of enzyme metabolism is noted, a decrease in the plasma concentration of warfarin in the blood (with combined use, an increase in the dose of warfarin may be required);
- rifampicin: warfarin metabolism increases (combined use should be avoided);
- nafcillin: the anticoagulant effect of warfarin decreases;
- rofecoxib: the mechanism of drug interaction has not been established;
- antidepressants (trazodone, mianserin): there is evidence that combined use with trazodone leads to a decrease in INR and prothrombin time, but the mechanism of this interaction is unknown. The mechanism of interaction with mianserin is also unknown;
- barbiturates, drugs with antiepileptic action: warfarin metabolism increases;
- azathioprine: the absorption of warfarin decreases, and the metabolism increases;
- chlorthalidone, spironolactone: diuretics with pronounced hypovolemic action can lead to an increase in the concentration of coagulation factors, which reduces the effect of warfarin;
- chlordiazepoxide, glutethimide, mercaptopurine, vitamin C: the anticoagulant effect of warfarin decreases;
- cyclosporine: its concentration increases, also due to the effect on metabolism, its therapeutic effect is enhanced;
- St. John's wort preparations: there is an increase in the metabolism of warfarin, carried out by CYP1A2, CYP3A4 (metabolism of R-warfarin) and CYP2C9 (metabolism of S-warfarin); after the end of the use of St. John's wort, the preservation of the effect of enzyme induction can be observed for 14 days. A careful monitoring of INR is shown, since with the abolition of St. John's wort, its level may increase. After this, the appointment of warfarin is possible;
- vitamin K: warfarin blocks the biosynthesis of vitamin K-dependent coagulation factors;
- ginseng: it is possible to induce the transformation of warfarin in the liver (combined use should be avoided);
- troglitazone: as a result of changes in the metabolism of warfarin, a decrease in the concentration or weakening of the effect of warfarin is noted;
- Foods containing vitamin K: the effect of warfarin is weakened. During therapy, it is necessary to carefully eat foods such as olive oil, amaranth greens, broccoli, avocado, spinach, soybeans, watercress, turnip greens, green mustard, mint, parsley, lettuce, cucumber peel, cabbage and Brussels sprouts, spring onions, chaillot leaves, canola oil, coriander (cilantro), onions, red seaweed, chicory, pistachios, kiwi fruits, peas, tea leaves.
Drugs, when combined with which the effect of warfarin is enhanced:
- cimetidine: there is a pronounced inhibitory effect on the cytochrome P 450 system, which leads to a decrease in the metabolism of warfarin (combined use is not recommended; cimetidine can be replaced by ranitidine or famotidine);
- metolazone, thienilic acid, tegafur, trastuzumab, flutamide, narcotic analgesics (dextropropoxyphene), levamisole, glibenclamide, omeprazole, digoxin, propranolol, glucagon, allopurinol, tetracyclines, sulfanilamides, sulpharynol is enhanced;
- clopidogrel, abciximab, eptifibatide, tirofiban, heparin: the effect of warfarin is enhanced as a result of additional effects on the hematopoietic system;
- ethacrynic acid: the effect of warfarin is enhanced due to its displacement from the bonds with proteins;
- amiodarone: after one week of combined use, the metabolism of warfarin decreases; after discontinuation of amiodarone, this effect may persist for 1–3 months;
- quinidine: the synthesis of blood clotting factors is reduced;
- lovastatin, simvastatin, fluvastatin, rosuvastatin, bezafibrate, gemfibrozil, clofibrate, fenofibrate (lipid-lowering drugs): with combined use, there is competition for metabolism, which is mediated by CYP2C9 and CYP3A4;
- diazoxide: it is possible to replace warfarin, bilirubin or other highly protein-bound substance from protein bonds;
- ticlopidine: the risk of bleeding increases, and therefore it is necessary to monitor the INR value;
- propafenone: warfarin metabolism is reduced;
- dipyridamole: the concentration of dipyridamole or warfarin increases, which is associated with the potentiation of their effects, while the likelihood of bleeding (hemorrhages) increases;
- steroid hormones (including testosterone, danazol): warfarin metabolism decreases, and / or there is a direct effect on the coagulation and fibrinolysis systems;
- miconazole (including in the form of an oral gel): the own clearance of warfarin decreases, while the free fraction of warfarin in the blood plasma increases; there is a decrease in the metabolism of warfarin, which is mediated by enzymes of the cytochrome P 450 system;
- cephalosporins (cefamandol, cephalexin, cefmenoxime, cefmetazole, cefoperazone, cefuroxime): the effect of warfarin is enhanced due to the suppression of the synthesis of vitamin K-dependent coagulation factors and other mechanisms;
- sulfinpyrazone: due to a decrease in its metabolism and a weakening of the connection with proteins, the anticoagulant effect is enhanced;
- penicillins in high doses (amoxicillin, cloxacillin): the likelihood of bleeding (including bleeding from the nose, gums, dark stools, or the appearance of atypical bruising) increases;
- agents that affect the thyroid gland: there is an increase in the metabolism of vitamin K-dependent coagulation factors;
- chloramphenicol: the metabolism of warfarin is reduced, since chloramphenicol has a pronounced inhibitory effect on the cytochrome P 450 system (combined use is not recommended);
- trimethoprim / sulfamethoxazole: the metabolism of warfarin decreases, and its displacement from the sites of binding to plasma proteins is also noted;
- quinolones (grepafloxacin, ciprofloxacin, ofloxacin, norfloxacin, nalidixic acid), macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin), antifungal agents (itraconazole, fluconazole, ketoconazole): metabolism decreases;
- acetylsalicylic acid: warfarin is displaced from the binding sites with albumin, the metabolism of warfarin is limited;
- codeine: the combination of codeine and paracetamol leads to increased activity of warfarin;
- leflunomide: there is a limitation of CYP2C9-mediated metabolism of warfarin;
- non-steroidal anti-inflammatory drugs (celecoxib, indomethacin, azapropazone, oxyfenbutazone, feprazone, piroxicam, tolmetin, sulindac and others, except for COX-2 inhibitors): there is competition for the metabolism carried out by CYP2C9;
- paracetamol (acetaminophen, especially after 1-2 weeks of constant use): affects the formation of coagulation factors and limits the metabolism of warfarin (when using paracetamol in a daily dose of up to 2000 mg, the interaction does not appear);
- fluorouracil, capecitabine: the synthesis of CYP2C9, which metabolizes warfarin, decreases;
- chloral hydrate: the mechanism of drug interaction has not been studied;
- antidepressants - SSRIs (selective serotonin reuptake inhibitors), including fluoxetine, paroxetine, fluvoxamine, sertraline: warfarin metabolism is limited; there is a suggestion that SSRIs limit the isoenzyme CYP2C9, which metabolizes the most potent isomer S-warfarin. You also need to take into account that warfarin and SSRIs strongly bind to albumin, therefore, with simultaneous use, the likelihood of one of them being displaced from the protein binding sites increases;
- drugs with antiepileptic action (phenytoin, phosphenytoin): warfarin metabolism increases, warfarin is displaced from the sites of binding to plasma proteins;
- phenylbutazone: the metabolism of warfarin decreases, warfarin is displaced from the sites of binding to plasma proteins (combined use should be avoided);
- Ifosfamide: suppression of CYP3A4 is noted;
- tramadol: there is competition for CYP3A4-mediated metabolism;
- tamoxifen: as a CYP2C9 inhibitor, tamoxifen can increase the serum concentration of warfarin, which is associated with a decrease in its metabolism;
- imatinib: competitive suppression of the CYP3A4 isoenzyme and suppression of CYP2C9 and CYP2D6 mediated metabolism of warfarin is observed;
- cyclophosphamide: as an antineoplastic agent, may increase the risk of altering the anticoagulant effect of warfarin;
- methotrexate: due to a decrease in the biosynthesis of procoagulant factors in the liver, the effect of warfarin is enhanced;
- alpha and beta interferon: there is an increase in the anticoagulant effect and an increase in the serum concentration of warfarin (with combined use, a decrease in the dose of warfarin is required);
- etoposide: the anticoagulant effect of coumarins may be enhanced;
- disulfiram: warfarin metabolism is reduced;
- zafirlukast: due to changes in its metabolism, it is possible to increase the concentration or increase the effect of zafirlukast;
- influenza vaccine, proguanil: the anticoagulant effect of warfarin may be enhanced;
- cranberry: CYP2C9 mediated metabolism of warfarin is reduced;
- angelica officinalis, papaya, ginkgo, sage, garlic: as a result of potentiation of the anticoagulant / antiplatelet effect, the risk of bleeding may increase;
- tonic drinks containing quinine: when consuming a large number of drinks, it may be necessary to reduce the dose of warfarin, which is associated with a decrease in the biosynthesis of procoagulant factors in the liver.
Other possible interactions:
- disopyramide: it is possible to weaken / increase the anticoagulant effect of warfarin;
- ethanol: possible induction or inhibition of warfarin metabolism;
- coenzyme-Q10: due to the homogeneity of the chemical structure with vitamin K, the effect of warfarin may be enhanced or suppressed;
- oral hypoglycemic agents (sulfonylurea derivatives): warfarin can lead to an increase in their action.
If it is necessary to combine the use of Warfarin Nycomed with the above drugs, INR control should be carried out at the beginning of therapy, after 2-3 weeks (preferably) and after its end.
Analogs
Warfarin Nycomed analogs are: Warfarin, Marevan, Warfarin-OBL, Warfarex.
Terms and conditions of storage
Store at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Warfarin Nycomed
Reviews about Warfarin Nycomed are mostly positive. The advantages include efficiency, affordable cost, convenient dosing regimen. The disadvantages are the need for constant monitoring of the INR level, side effects, namely increased bleeding, which is especially dangerous in trauma.
The price of Warfarin Nycomed in pharmacies
The approximate price for Warfarin Nycomed 2.5 mg is 89-110 rubles. (50 tablets in a package) or 149-175 rubles. (100 tablets in a package).
Warfarin Nycomed: prices in online pharmacies
Drug name Price Pharmacy |
Warfarin Nycomed 2.5 mg tablets 50 pcs. RUB 90 Buy |
Warfarin Nycomed 2.5 mg tablets 100 pcs. 143 r Buy |
Warfarin Nycomed tablets 2.5mg 100 pcs. 147 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!