WARNING: BLEEDING RISK
Warfarin sodium can cause major or fatal bleeding. Bleeding is more likely to occur during the starting period and with a higher dose (resulting in a higher INR). Risk factors for bleeding include high intensity of anticoagulation (INR > 4.0), age ≥ 65, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs (see PRECAUTIONS) and long duration of warfarin therapy. Regular monitoring of INR should be performed on all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed about prevention measures to minimize risk of bleeding and to report immediately to physicians signs and symptoms of bleeding (see PRECAUTIONS: Information for Patients).

DESCRIPTION
Warfarin sodium (crystalline) is an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors. Chemically, it is 3-(α-acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the R-and S-enantiomers. Crystalline warfarin sodium is an isopropanol clathrate. The crystallization of warfarin sodium virtually eliminates trace impurities present in amorphous warfarin. Its molecular formula is C19H15NaO4, and its structural formula may be represented by the following:

Crystalline warfarin sodium occurs as a white, odorless, crystalline powder, is discolored by light and is very soluble in water; freely soluble in alcohol; very slightly soluble in chloroform and in ether.

Warfarin sodium tablets, USP for oral administration contain either 1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg or 10 mg warfarin sodium, USP. In addition they also contain the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, stearic acid and,

1 mg tablets: FD&C Red No. 40 Aluminum Lake
2 mg tablets: FD&C Blue No. 2 Aluminum Lake and FD&C Red No. 40 Aluminum Lake
2.5 mg tablets: D&C Yellow No. 10 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake
3 mg tablets: FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake
4 mg tablets: FD&C Blue No. 1 Aluminum Lake
5 mg tablets: FD&C Yellow No. 6 Aluminum Lake
6 mg tablets: FD&C Blue No. 1 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake
7.5 mg tablets: D&C Yellow No. 10 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake
10 mg tablets: Dye Free

CLINICAL PHARMACOLOGY
Warfarin sodium and other coumarin anticoagulants act 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. Half-lives of these clotting factors are as follows: Factor II – 60 hours, VII – 4 to 6 hours, IX - 24 hours, and X – 48 to 72 hours. The half-lives of proteins C and S are approximately 8 hours and 30 hours, respectively. The resultant in vivo effect is a sequential depression of Factor VII, Protein C, Factor IX, Protein S, and Factor X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. The vitamin promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins which are essential for biological activity.

Mechanis