Overview
11 DESCRIPTION Warfarin sodium tablets, USP contain warfarin sodium, an anticoagulant that acts by inhibiting vitamin K-dependent coagulation factors. The chemical name of warfarin sodium is 3-(α-acetonylbenzyl)-4-hydroxycoumarin sodium salt, which is a racemic mixture of the R - and S -enantiomers. Crystalline warfarin sodium is an isopropanol clathrate.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. Vitamin K promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins that are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K 1 epoxide [see Clinical Pharmacology ( 12.5 )] . 12.
Indications
- 1 INDICATIONS AND USAGE Warfarin sodium tablets are indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Limitations of Use Warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage.
Common Doses
- 100 mg
- 5 mg
- 10 mg
- 7 mg
Dosage
2 DOSAGE AND ADMINISTRATION Individualize dosing regimen for each patient, and adjust based on INR response. ( 2.1 , 2.2 ) Knowledge of genotype can inform initial dose selection. ( 2.3 ) Monitoring: Obtain daily INR determinations upon initiation until stable in the therapeutic range. Obtain subsequent INR determinations every 1 to 4 weeks. ( 2.4 ) Review conversion instructions from other anticoagulants. ( 2.8 ) 2.1 Individualized Dosing The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the patient’s International Normalized Ratio...
Black Box Warning
WARNING: BLEEDING RISK Warfarin sodium can cause major or fatal bleeding [see Warnings and Precautions ( 5.1 )] . Perform regular monitoring of INR in all treated patients [see Dosage and Administration ( 2.1 )] . Drugs, dietary changes, and other factors affect INR levels achieved with warfarin sodium therapy [see Drug Interactions ( 7 )] . Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding [see Patient Counseling Information ( 17 )] . WARNING: BLEEDING RISK See full prescribing information for complete boxed warning.
Contraindications
- 4 CONTRAINDICATIONS Warfarin sodium is contraindicated in: Pregnancy Warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.1 )] . Warfarin sodium can cause fetal harm when administered to a pregnant woman. Warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion...
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions to warfarin sodium are discussed in greater detail in other sections of the labeling: Hemorrhage [see Boxed Warning, Warnings and Precautions (5.1), and Overdosage ( 10 )] Tissue Necrosis [see Warnings and Precautions ( 5.2 )] Calciphylaxis [see Warnings and Precautions ( 5.3 )] Acute Kidney Injury [see Warnings and Precautions ( 5.4 )] Systemic Atheroemboli and Cholesterol Microemboli [see Warnings and Precautions ( 5.5 )] Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Concomitant use of drugs that increase bleeding risk, antibiotics, antifungals, botanical (herbal) products, and inhibitors and inducers of CYP2C9, 1A2, or 3A4. ( 7 ) Consult labeling of all concurrently used drugs for complete information about interactions with warfarin sodium or increased risks for bleeding. ( 7 ) 7.1 General Information Drugs may interact with warfarin sodium through pharmacodynamic or pharmacokinetic mechanisms.