Warfarin-Alium, tablets 2.5mg 100 pcs

Warfarin s belongs to the group of anticoagulants – drugs that prevent blood clotting, and is intended for long-term use.

It has an indirect anticoagulant effect, inhibiting in the liver the synthesis of a number of factors involved in the regulation of blood clotting.

Warfarex prevents the formation of new blood clots and prevents the increase of already formed ones.

Indications

Treatment and prevention of thrombosis and embolism of blood vessels: Acute venous thrombosis and pulmonary embolism; postoperative thrombosis; recurrent myocardial infarction; as an adjunct to surgical or drug (thrombolytic) treatment of thrombosis; and in electrical cardioversion of atrial fibrillation; recurrent venous thrombosis; recurrent pulmonary embolism; prosthetic heart valves and vessels (can be combined with acetylsalicylic acid); peripheral, coronary and cerebral artery thrombosis; secondary prevention of thrombosis and thromboembolism after myocardial infarction and atrial fibrillation.

Active ingredient

Composition

On 1 tablet:

the active ingredient:

warfarin sodium clathrate – 2.71 mg, in terms of warfarin sodium – 2.5 mg;

excipients:

magnesium stearate,

lactose monohydrate,

corn starch,

calcium hydrophosphate dihydrate,

povidone K-30.

How to take, the dosage

Overly, in a single dose, at the same time of day.

The initial dose is 2.5-5 mg/day. Further dosing regime is determined individually depending on results of prothrombin time or INR determination. Prothrombin time should be increased 2-4 times of initial one and INR should be 2.2-4.4, depending on disease, thrombosis danger, bleeding risk and individual peculiarities of a patient.

In determining INR, the sensitivity index of thromboplastin should be taken into account and used as a correction factor (1.22 – when using domestic thromboplastin from rabbit brain “Neoplast” and 1.2 – when using thromboplastin by “Roche Diagnostics”). Older and weakened patients are usually prescribed lower doses of the drug.

Before the upcoming surgery (if there is a high risk of thromboembolic complications) the treatment is started 2-3 days before surgery.

In case of acute thrombosis, treatment is carried out in combination with heparin until the effect of oral anticoagulant therapy is fully apparent (not before 3-5 days of treatment).

In heart valve replacement, acute venous venous thrombosis or thromboembolism (in the initial stages), left ventricular thrombosis and for the prevention of myocardial ischemia, the effective effect noted at INR 2.8-4 should be sought.

In atrial fibrillation and maintenance therapy for venous thrombosis and thromboembolism, a moderate anticoagulation effect (INR 2.8-3) is sought.

When warfarin is used together with acetylsalicylic acid, the INR should be between 2 and 2.5.

In children

The 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 adjusted according to INR values. The recommended INR levels are the same as in adults. The decision to prescribe vrfarin in children should be made by an experienced specialist. Treatment should be conducted under the supervision of a pediatrician.

The duration of treatment depends on the condition of the patient. Treatment can be withdrawn immediately.

Interaction

Concomitant use with anticoagulants and drugs with antiaggregant activity increases the risk of bleeding.

Concomitant use with anticholinergic agents may cause memory and attention disorders in elderly patients.

Concomitant use with microsomal liver enzyme inhibitors increases the anticoagulant effect of warfarin and increases the risk of bleeding.

Concomitant use with hypoglycemic agents sulfonylurea derivatives may increase their hypoglycemic effect.

When used concomitantly the anticoagulant effect of warfarin decreases: inducers of microsomal liver enzymes (including barbiturates, phenytoin, carbamazepine), glutethimide, griseofulvin, dicloxacillin, coenzyme Q10, mianserine, paracetamol, retinoids, rifampicin, sucralfate, phenazone, Colatiramine, glutethimide, vitamin K, acitretin, diuretics (spironolactone and chlorthalidone), aminoglutethimide, mercaptopurine, mitotane, cisapride, ginseng products, glucagon.

The anticoagulant effect of warfarin may be enhanced and the risk of bleeding increased with concomitant use with heparin, NSAIDs (including acetylsalicylic acid), pyrazolone derivatives (including with phenylbutazone, sulfinpyrazone), tramadol, dextropropoxyphene, combination of paracetamol and codeine, antiarrhythmic agents (including with amiodarone, quinidine, propafenone, moratsizine), antimicrobial and antifungal agents (including with chloramphenicol, metronidazole, cefamandole, cefmetazole, cefoperazone, cefazolin, erythromycin, azithromycin, roxithromycin, clarithromycin, co-trimoxazole, miconazole, ketoconazole, itraconazole, fluconazole, nalidixic acid, ciprofloxacin, norfloxacin, ofloxacin, aminosalicylic acid, benzylpenicillin, doxycycline, isoniazid, neomycin, tetracyclines, aztreonam), glibenclamide valproic acid, quinine, proguanil, cyclophosphamide, methotrexate, fluorouracil, with combinations of etoposide and vindesine or carboplatin, ifosfamide with mesna, tamoxifen, flutamide, interferon alfa (for chronic hepatitis C), interferon beta, saquinavir, clofibrate, ciprofibrate, fenofibrate, gemfibrozil, cimetidine, lovastatin, fluvastatin, simvastatin, piracetam, danazol, tramadol.

In concomitant use with tricyclic antidepressants, disopyramide, felbamate, terbinafine, allopurinol, dipyridamole, chloral hydrate, ranitidine, ascorbic acid, tocopherol the data on drug interaction is controversial.

In patients with chronic alcoholism taking disulfiram an increase in the effects of warfarin has been observed.

The absorption and bioavailability of warfarin are decreased when concomitant use with colestyramine.

In concomitant use with ticlopidine liver damage has been described. The anticoagulant effect of warfarin is not changed.

Concomitant use with phenazone decreases plasma concentrations of warfarin.

In concomitant use with phenytoin, an initial increase in anticoagulant activity with a subsequent decrease has been reported.

In concomitant use with fluoxetine, trazodone, vitamin E there have been reports of increased effect of warfarin.

In concomitant use with cyclosporine a mutual reduction of the effects is observed.

Concomitant use with enoxacin decreases clearance of R-isomer but not S-isomer, while prothrombin time is not increased.

Concomitant use with etacrynic acid may increase diuretic effect, hypokalemia, because as a result of competition for binding to plasma proteins the concentration of free (active) etacrynic acid increases.

In regular use of alcohol it is possible to reduce the effects of warfarin, apparently due to the induction of liver enzymes. However, the effects of warfarin may increase with liver damage.

Inadvertent ingestion of large amounts of alcohol may increase the effects of warfarin.

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Special Instructions

A mandatory requirement of warfarin therapy is that the patient adheres to the prescribed dose of the drug.

Patients with alcoholism and patients with dementia may not be able to adhere to the prescribed warfarin regimen. Conditions such as fever, hyperthyroidism, decompensated heart failure, and alcoholism with concomitant liver damage may increase the effect of warfarin. In hypothyroidism, the effect of warfarin may be reduced. In case of renal failure or nephrotic syndrome, the level of free plasma fraction of warfarin increases, which, depending on the concomitant diseases, may lead to both enhancement and reduction of the effect. In case of moderate hepatic insufficiency, the effect of warfarin is enhanced. In all of the above conditions, careful monitoring of MHO levels should be performed.

Patients receiving warfarin should be prescribed paracetamol, tramadol or opioids as analgesics. If a rapid antithrombotic effect is required, it is recommended that treatment be initiated with heparin administration; then combination therapy with heparin and warfarin should be given for 5-7 days until the target MHO level has been maintained for 2 days. To avoid coumarin necrosis, patients with hereditary antithrombotic protein C or S deficiency should be given heparin first. The concomitant initial loading dose should not exceed 5 mg. Heparin administration should be continued for 5-7 days.

During treatment with warfarin, ethanol should be abstained (risk of hypoprothrombinemia and bleeding).

In case of individual resistance to warfarin (rare), 5 to 20 shock doses of warfarin are needed to achieve therapeutic effect.

If warfarin administration is ineffective in these patients, other possible causes should be identified, among which are possible: concomitant administration of warfarin with other medications (see appropriate section of the instructions), inadequate diet, and laboratory errors.

The treatment of elderly patients should be conducted with special caution because the synthesis of clotting factors and hepatic metabolism in these patients is decreased, as a consequence of which excessive effect of warfarin may occur.

Contraindications

Hypersensitivity, acute bleeding, severe liver or kidney disease, severe arterial hypertension, acute DIC syndrome, protein C and S deficiency, hemorrhagic diathesis, thrombocytopenia, Peptic ulcer in acute stage, cerebral hemorrhage, alcoholism, renal insufficiency, pregnancy, hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Side effects

Most common: >1/10 – bleeding.

Often: >1/100, <1/10 – increased sensitivity to warfarin after long-term use.

Infrequent: >1/1,000, <1/100 – anemia, vomiting, abdominal pain, nausea, diarrhea.

Rare: >1/10,000, <1/1,000 – eosinophilia, increased liver enzyme activity, jaundice, rash, urticaria, pruritus, eczema, skin necrosis, vasculitis, hair loss, nephritis, urolithiasis, tubular necrosis.

Bleeding. The most common risk factor for intracranial hemorrhage. The likelihood of bleeding is increased if the INR is well above the target level. If bleeding has started at an INR that is within the target level, then there are other concomitant conditions that should be investigated.

Digestive system disorders. Vomiting, nausea, diarrhea.

Necrosis. Coumarin necrosis. In 90% of cases, necrosis develops in women. Lesions are seen from day 3 to day 10 of the drug and the etiology suggests insufficiency of antithrombotic protein C or S.

The palmar-treated syndrome. A very rare complication of warfarin therapy, its development is typical for men with atherosclerotic diseases.

Others. Hypersensitivity reactions manifested as skin rash and characterized by reversible increase in liver enzyme concentrations, cholestatic hepatitis, vasculitis, priapism, reversible alopecia and tracheal calcification. Independent risk factors for serious bleeding during warfarin treatment are: older age, high intensity of concomitant anticoagulant and antiaggregant therapy, a history of strokes and gastrointestinal bleeding. The risk of bleeding is increased in patients with CYP2C9 gene polymorphism.

Overdose

The treatment efficacy rate is on the border of bleeding development, so the patient may have minor bleeding, such as microhematuria, bleeding gums, etc. In mild cases, it is sufficient to reduce the dose of the drug or stop treatment for a short time. In minor bleeding it is sufficient to discontinue the drug until the INR reaches the target level.

In case of severe bleeding – administration of vitamin K (intravenous) and activated charcoal, clotting factor concentrate or fresh frozen plasma. If oral anticoagulants are indicated for further administration, large doses of vitamin K should be avoided, as resistance to warfarin develops within 2 weeks.

After treatment, long-term follow-up of the patient is necessary, given that the half-life of warfarin is 20-60 hours.