(S)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyron

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

P203, P260, P262, P264, P270, P271, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P318, P319, P320, P321, P330, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H360 (97.4%): May damage fertility or the unborn child [Danger Reproductive toxicity]

P203, P260, P264, P270, P273, P280, P318, P319, P405, and P501 (click each P-code to see the statement)

Repr. 1A (97.4%)

Reproductive toxicity - category 1A

Repr. 1A

The primary antidote to warfarin poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses warfarin can affect the body for many months, and the antidote must be administered regularly for a long period of time. (L1257)

(S)-warfarin has known human metabolites that include (S)-6-Hydroxywarfarin, (S)-10-Hydroxywarfarin, (S)-7-Hydroxywarfarin, and (S)-4'-Hydroxywarfarin.

Metabolized stereo- and regio-selectively by hepatic microsomal enzymes. S-warfarin is predominantly metabolized by cytochrome P450 (CYP) 2C9 to yield the 6- and 7-hydroxylated metabolites. R-warfarin is metabolized by CYP1A1, 1A2, and 3A4 to yield 6-, 8-, and 10-hydroxylated metabolites. Hydroxylated metabolites may be further conjugated prior to excretion into bile and urine. UGT1A1 appears to be responsible for producing the 6-O-glucuronide of warfarin, with a possibly contribution from UGT1A10. Five UGT1As may be involved in the formation of 7-O-glucuronide warfarin. S-warfarin has higher potency than R-warfarin and genetic polymorphisms in CYP2C9 may dramatically decrease clearance of and increase toxicity of the medication. In man, the dextrowarfarin enantiomorph is metabolized by side chain reduction to a secondary alcohol, whereas levowarfarin is metabolized by oxidation of the ring, primarily to 7-hydroxywarfarin. These inactive metabolic products are to some extent conjugated with glucuronic acid, undergo an enterohepatic circulation, & are ultimately excreted in urine & stool. (A613) Route of Elimination: The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile. Half Life: R-warfarin t_1/2=37-89 hours; S-warfarin t_1/2=21-43 hours.

Warfarin is an anticoagulant drug and rodenticide derived from coumarin. As a drug it is used for the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis. (A308)