Instructions for use WARFAREX
The use of anticoagulants increases the risk of bleeding, the degree of which depends on the intensity and duration of treatment.
Warfarex should be used with caution when carrying out therapeutic and diagnostic procedures and treating diseases and injuries in which the risk of bleeding is increased, when treating elderly and debilitated patients, patients suffering from severe diabetes mellitus, liver or kidney failure.
The simultaneous use of Warfarex with urokinase and streptokinase is not recommended.
Warfarex has a small breadth of therapeutic action, so during the treatment period the INR should be regularly determined in order to select an adequate maintenance dose if necessary.
During the treatment period, regular urine analysis is also necessary to identify possible hematuria, if it occurs, the possibility of using the medication and/or the dosage regimen should be reconsidered.
In patients receiving anticoagulants, the INR should be determined before all procedures associated with a risk of bleeding. Before minor surgical interventions, a maintenance dose is selected that ensures a decrease in the INR value to the minimum therapeutic level. The procedure is carried out carefully, using local hemostatic agents. If the scope of surgery is more significant, it may be necessary to discontinue the use of anticoagulants. Therefore, the physician must weigh the risk of undergoing surgery and stopping anticoagulant treatment.
The individual sensitivity of patients to the action of Warfarex may be reduced or increased. It should be borne in mind that the body's response to the use of anticoagulants can change under the influence of many endogenous and exogenous factors (including diet, living conditions, health status, use of other medications).
The effect of the drug may be enhanced by hematological and oncological diseases, collagenosis, chronic heart failure, hyperthyroidism, hyperthermia, liver dysfunction, diarrhea, vitamin K deficiency. The anticoagulant effect may be reduced in patients with hypothyroidism, hyperlipidemia, edema, nephrotic syndrome. In these cases, more frequent laboratory tests and dose adjustment are necessary.
If it is necessary to use the drug in patients with lactase intolerance, it should be kept in mind that Warfarex contains lactose.
Use in pediatrics
The effectiveness and safety of the drug in children has not been sufficiently proven in clinical studies, but there is evidence of the effectiveness of warfarin to eliminate thromboembolic complications in pediatrics. Clinical experience suggests that a stable INR level is difficult to maintain and requires more frequent dosage adjustments.
Impact on the ability to drive vehicles and operate machinery
There are no data on the adverse effects of Warfarex on the ability to drive vehicles and operate other machinery.
Warfarex, 5 mg, tablets, 100 pcs.
High levels of vitamin K in foods (spinach, broccoli, lettuce and other leafy vegetables) may reduce the effect of Warfarex®. However, you should not change your diet too abruptly or use vitamins and nutritional supplements without consulting your doctor.
Smoking may reduce the anticoagulant effect of the drug.
The effect of Warfarex® may change under the influence of a large number of drugs.
NSAIDs, dipyridamole, valproic acid, cytochrome P450 inhibitors, cimetidine, chloramphenicol, laxatives - increase the risk of bleeding. The combined use of these drugs and Warfarex® should be avoided (cimetidine can be replaced with ranitidine or famotidine). If treatment with chloramphenicol is necessary, anticoagulant therapy may be temporarily discontinued. Diuretics can reduce the effect of anticoagulants (in case of pronounced hypovolemic effect, which can lead to an increase in the concentration of coagulation factors). Weaken the effect: barbiturates, vitamin K, glutethimide, griseofulvin, dicloxacillin, carbamazepine, mianserin, paracetamol, retinoids, rifampicin, sucralfate, phenazone, cholestyramine. Enhance the effect: allopurinol, amiodarone, anabolic steroids (alkylated at position C-17), acetylsalicylic acid and other NSAIDs, heparin, glibenclamide, glucagon, danazol, diazoxide, disopyramide, disulfiram, isoniazid, ketoconazole, clarithromycin, clofibrate, levamisole, metronidazole, miconazole, nalidixic acid, nilutamide, omeprazole, paroxetine, proguanil, oral hypoglycemic agents - sulfonamide derivatives, sulfonamides, tamoxifen, thyroxine, quinine, quinidine, fluvoxamine, fluconazole, fluorouracil, quinolones, chloral hydrate, chloramphenicol, cephalosporins, cimeti din, erythromycin, ethacrynic acid , ethanol. When using Warfarex® in combination with the above drugs, it is necessary to monitor the INR at the beginning and end of treatment and, if possible, after 2-3 weeks from the start of therapy. When using drugs that may increase the risk of bleeding due to a decrease in normal coagulation (inhibition of blood clotting factors or liver enzymes), the anticoagulant strategy should be determined by the availability of laboratory monitoring. If frequent laboratory monitoring is possible, then if therapy with such drugs is necessary, the dose of Warfarex® can be reduced by 5–10%. If laboratory monitoring is difficult, treatment with Warfarex® should be discontinued if these drugs need to be prescribed.
Warfarex®
Orally in one dose, preferably at the same time of day. The duration of treatment is determined by the doctor in accordance with the indications for use.
Control during treatment
Before starting treatment, the international normalized ratio (INR) is determined. Subsequently, laboratory monitoring is carried out regularly every 4-8 weeks. The duration of treatment depends on the clinical condition of the patient. Treatment can be canceled immediately.
Adults
For patients with normal body weight and a baseline INR of less than 1.2, warfarin 10.5 mg is prescribed for three consecutive days. The dose is then calculated according to the table below, based on the INR measurement on the fourth day of therapy.
In outpatient settings and in patients with thrombophilias (hereditary protein C or S deficiency), the recommended starting dose of warfarin is 4.5 mg for three consecutive days. The dose is then calculated according to the table below, based on the INR measurement on the fourth day of therapy.
For elderly patients, patients with low body weight with an INR greater than 1.2, or with concomitant diseases, or receiving any medications that affect the effectiveness of anticoagulant therapy, the recommended starting dose of warfarin is 4.5 mg for two consecutive days. The dose is then calculated according to the table below, based on the INR measurement on the third day of therapy.
| Day | INR | Warfarin dose, mg/day |
| 1 | — | 10,5 (4,5*) |
| 2 | — | 10,5 (4,5*) |
| 3 | <2,0 | 10,5 (4,5*) |
| from 2.0 to 2.4 | 6 | |
| from 2.5 to 2.9 | 3 | |
| from 3.0 to 3.4 | 1,5 | |
| >4,0 | miss one day | |
| 4-6 | <1,4 | 10,5 |
| from 1.4 to 1.9 | 7,5 | |
| from 2.0 to 2.4 | 6 | |
| from 2.5 to 2.9 | 4,5 | |
| from 3.0 to 3.9 | 3 | |
| from 4.0 to 4.5 | skip one day, then 1.5 | |
| >4,5 | skip two days, then 1.5 | |
| 7- | from 1.1 to 1.4 | weekly warfarin dose increased by 20% |
| from 1.5 to 1.9 | weekly warfarin dose increased by 10% | |
| from 2.0 to 3.0 | dose is maintained | |
| from 3.1 to 4.0 | decreases by 10% | |
| >4,5 | skip until INR drops to <4.5, then continue with dose reduced by 20% |
*Initial doses indicated for patients with hereditary protein S or C deficiency.
The INR is measured daily until a stable target level is reached, which is usually set on days 5-6 of treatment.
In case of large deviations in INR levels or in patients with liver disease or diseases affecting the absorption of vitamin K, measurement intervals may be less than 4 weeks. Prescribing new or discontinuing previously taken medications requires additional INR measurements.
For long-term therapy, adjustments are made to the weekly dose of warfarin in accordance with the table above. If the dose requires adjustment, the next INR measurement should be performed 1 or 2 weeks after the adjustment. After this, measurements continue until 4 weekly intervals are reached.
In the absence of the possibility of routine INR monitoring required when using warfarin, switch to other oral anticoagulants (dabigatran, apixaban, rivaroxaban). It is important to avoid the simultaneous use of warfarin and another drug in therapeutic doses. It is necessary to discontinue warfarin and then monitor the INR daily.
When the INR reaches <2.0 (usually within three days after warfarin is discontinued), apixaban or dabigatran is started; When the INR reaches <3.0, rivaroxaban is started.
Patients who have previously taken warfarin
The recommended starting dose is twice the known maintenance dose of warfarin and is given for the first 2 days. Treatment is then continued with a known maintenance dose. On the 5th day of treatment, the INR is monitored and the dose is adjusted in accordance with this indicator.
It is recommended to maintain an INR of 2 to 3 in the case of prevention and treatment of venous thrombosis, pulmonary embolism, atrial fibrillation, dilated cardiomyopathy, complicated heart valve diseases, and heart valve replacement with bioprostheses.
Higher INR levels of 2.5 to 3.5 are recommended for mechanical heart valve replacement and complicated acute myocardial infarction.
Children
Data on the use of warfarin in children are limited.
The starting dose is usually 0.2 mg/kg per day for normal liver function and 0.1 mg/kg per day for impaired liver function. The maintenance dose is selected in accordance with the INR values. Recommended INR levels are the same as for adults.
The decision to prescribe warfarin in children should be made by an experienced specialist. Treatment should be carried out under the supervision of an experienced pediatrician. Doses are selected in accordance with the table below.
| I. Day 1 | If the baseline INR value is from 1.0 to 1.3, then the loading dose is 0.2 mg/kg body weight. |
| II. Days 2 to 4, if the INR value is: | Actions: |
| from 1 to 1.3 | Repeat loading dose; |
| from 1.4 to 1.9 | 50% of loading dose; |
| from 2.0 to 3.0 | 50% of loading dose; |
| from 3.1 to 3.5 | 25% of loading dose; |
| >3,5 | Stop the drug until the INR is <3.5, then resume treatment at a dose equal to 50% of the previous dose. |
| III . Maintenance if the INR value is: | Actions (weekly dose): |
| from 1 to 1.3 | Increase the dose by 20%; |
| from 1.4 to 1.9 | Increase the dose by 10%; |
| from 2.0 to 3.0 | Without changes; |
| from 3.1 to 3.5 | Reduce dose by 10%; |
| >3,5 | Stop warfarin until the INR is <3.5, then resume treatment at a dose 20% less than the previous dose. |
Patients with liver failure
Impaired liver function increases sensitivity to warfarin because the liver produces clotting factors and also metabolizes warfarin. In this group of patients, careful monitoring of INR values is necessary.
Patients with kidney failure
In patients with impaired renal function, the dose of warfarin should be reduced and careful monitoring should be performed.
Planned (elective) surgical interventions
Pre-, peri- and post-operative anticoagulant therapy is carried out as indicated below (if urgent reversal of the oral anticoagulant effect is necessary - see section “Overdose”).
| Determine the INR one week before the scheduled surgery. |
| Stop taking warfarin 1-5 days before surgery. In case of a high risk of thrombosis, low molecular weight heparin is administered subcutaneously to the patient for prophylaxis. The duration of the pause in taking warfarin depends on the INR. Warfarin is stopped: - 5 days before surgery, if INR>4.0 - 3 days before surgery, if the INR is from 3.0 to 4.0 - 2 days before surgery, if the INR is from 2.0 to 3.0 |
| Determine the INR the evening before surgery and administer 0.5-1.0 mg of vitamin K1 orally or intravenously if the INR is >1.8. |
| Consider the need for unfractionated heparin infusion or prophylactic low molecular weight heparin on the day of surgery. |
| Continue subcutaneous administration of low molecular weight heparin for 5-7 days after surgery with concomitant resumption of warfarin. |
| Continue warfarin at the usual maintenance dose on the same day in the evening after minor surgery and on the day the patient begins receiving enteral nutrition after major surgery. |
If you miss a dose of warfarin and notice it within 12 hours, take the missed dose as soon as possible. Take your next dose as usual. If more than 12 hours have passed since the missed dose, do not take it. Take your next dose as usual. If more than one dose is missed, you should consult your doctor for advice. Never take a double dose to replace a missed dose. It is recommended to keep a record of warfarin doses.
