Drug Name
Generic Name: Warfarin Sodium Tablets
Previously known as.
Trade Name.
English name：Warfarin Sodium Tablets
Hanyu Pinyin：Huflinn Pin
The chemical name of this product is: 3-(3-oxo-1-phenylbutyl)-4-hydroxy-2H-1-benzopyrandione sodium salt with isopropanol inclusion.
Structural formula.
Molecular formula: C19H15NaO4
Molecular weight: 330.31
【Properties】.
This product is sugar-coated tablet, which appears white after removing the sugar coating.
Pharmacology and Toxicology
This product is a medium-acting anticoagulant of bicoumarins. Its mechanism of action is to competitively counteract the effect of vitamin K, inhibit the synthesis of coagulation factors in hepatocytes, and also has the effect of reducing the thrombin-induced platelet aggregation reaction, so it has the function of anticoagulation and anti-platelet aggregation.
Pharmacokinetics]
Gastrointestinal absorption is rapid and complete, and the bioavailability is up to 100%. After absorption, it is 98%-99% bound to plasma proteins and can pass through the placenta, and very little in breast milk. It is mainly stored in the lung, liver, spleen and kidney. It is metabolized by the liver and the metabolites are excreted by the kidneys. The onset of action is 12-18 hours after taking the drug, with a peak anticoagulation of 36-48 hours and a maintenance of 3-6 d, t1/2 about 37 hours.
Indications
For patients who require long-term continuous anticoagulation.
① It can prevent the formation and development of thrombosis and is used for the treatment of thromboembolic diseases.
② Treatment of venous thrombosis after surgery or trauma, and as an adjunct to myocardial infarction.
③ It can be used prophylactically in patients with previous thromboembolic disease and those at risk of postoperative thrombotic complications.
Dosage
Oral, adult dose: avoid shock treatment oral dose of 3-4mg for the first 3 days (half a dose for the elderly, frail and diabetic patients), after 3 days, the maintenance dose of 2.5-5mg a day can be given (the dose can be adjusted with reference to the clotting time to make the INR value reach 2-3). Because of the slow onset of action of this product, there may be a transient hypercoagulable state in the first 3 days of treatment due to the inhibition of plasma anticoagulant cells. If the anticoagulant effect must be produced immediately, heparin can be applied at the same time at the beginning, and heparin can be discontinued after the product has fully exerted its anticoagulant effect.
Adverse effects]
Overdose may cause various kinds of bleeding. Early manifestations include petechiae, purpura, gum bleeding, epistaxis, prolonged wound bleeding, excessive menstrual flow, etc. Bleeding can occur at any site, especially in the urinary and digestive tracts. Intestinal wall hematoma can cause subacute intestinal obstruction, and subdural intracranial hematoma and puncture site hematoma can also be seen. Occasional adverse reactions include nausea, vomiting, diarrhea, pruritic rash, allergic reactions, and skin necrosis. Bilateral breast necrosis, microangiopathy or hemolytic anemia, and extensive skin gangrene may occur with large oral doses; a single overdose is particularly dangerous.
Contraindications
Contraindicated in patients with hepatic or renal impairment, severe hypertension, coagulation disorders with bleeding tendency, active ulcers, trauma, pre-eclampsia, recent surgery. Contraindicated during pregnancy.
Precautions]
(1) Should be used with caution in the elderly or during menstruation.
(2) Strictly control the indications and do not abuse this product in the absence of prothrombin assay.
(3) Individual differences are significant, so close observation should be made during treatment and dosage should be adjusted according to the INR value of prothrombin time. The oral mucosa, nasal cavity, subcutaneous bleeding and stool occult blood, hematuria, etc. should also be closely observed during the treatment period. Avoid unnecessary surgical operations during the medication period, stop the medication for 7 days for elective surgery, correct the PTINR value ≤1.6 for emergency surgery, and avoid overexertion and activities that may cause injury.
(4) If mild bleeding occurs, or if the prothrombin time (PT) has been significantly prolonged to more than 2.5 times normal, the drug should be reduced or discontinued immediately. For severe bleeding, vitamin Kl10-20mg can be injected to control bleeding, and if necessary, whole blood, plasma or prothrombin complex can be transfused.
(5) Since this product is an indirect-acting anticoagulant with a long half-life, its efficacy can be stabilized only after 5-7 days of administration, therefore, it is necessary to observe whether the maintenance amount is sufficient or not for 5-7 days before making a conclusion.
Pregnant women and nursing mothers
(1) It is likely to pass through the placenta and cause malformation. The use of this product during pregnancy can lead to “fetal warfarin syndrome”, the incidence of up to 5%-30%. The manifestation is epiphyseal separation, nasal hypoplasia, optic nerve atrophy, mental retardation, heart, liver, spleen, gastrointestinal tract, head and other malformations. The use of the product in the second trimester of pregnancy may cause bleeding and stillbirth, so it is prohibited in the early trimester and the second trimester of pregnancy. Low doses of heparin may be given to pregnant women with hereditary embolism and are subject to close laboratory monitoring.
(2) A small amount of warfarin can be secreted by breast milk, lactating women take 5-10mg daily, the blood concentration is generally 0.48-1.8μg/ml, the drug concentration in breast milk and infant plasma is very low, the effect on the infant is small.
Children’s medication
The dose should be adjusted according to individual needs.
For elderly patients
It should be used with caution in the elderly, and the dosage should be reduced and individualized.
Drug Interactions
Drugs that enhance the anticoagulant effect of this product include: aspirin, sodium salicylate, glucagon, quinidine, indomethacin, protamine, quinine, diuretic acid, methylsulfonylurea, metronidazole, allopurinol, erythromycin, chloramphenicol, certain aminoglycoside antibiotics, cephalosporins, phenylephrine, cimetidine, clobetine, dextrothyroxine, acetaminophen, etc.
Drugs that reduce the anticoagulant effect of this product: phenytoin sodium, barbiturates, oral contraceptives, estrogen, clofentezine, rifampicin, vitamin K, chlorthalidone, spironolactone, paracetamol, corticosteroids, etc.
Drugs that cannot be combined with this product: epinephrine hydrochloride, amikacin, vitamin B12, m-hydroxylamine, contractions, chlorpromazine hydrochloride, vancomycin hydrochloride, etc.
The combination of this product and chloral hydrate, its efficacy and toxicity are enhanced, should be used with reduced caution. The anticoagulant effect of this product is also affected by the impaired absorption or decreased synthesis of vitamin K.
Drug overdose
Specification
(1) 2.5mg (2) 5mg
Storage
Store under shade and seal.