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Interaction of Sodium Warfarin and Disulfiram (Antabuse®) in Man

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Supported in part by grant HE 8058-09, U.S. Public Health Service, Washington, D.C.

▸Requests for reprints should be addressed to Robert A. O'Reilly, M.D., Santa Clara Valley Medical Center, 751 S. Bascom Ave., San Jose, Calif. 95128.

San Jose and San Francisco, California

Ann Intern Med. 1973;78(1):73-76. doi:10.7326/0003-4819-78-1-73
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To evaluate the interaction of sodium warfarin and disulfiram (Antabuse®), a single dose (1.5 mg/kg body weight) and a 21-day course of sodium warfarin were administered orally, with and without disulfiram orally, to eight normal subjects. A significant augmentation of both the hypoprothrombinemia (P < 0.01) and the plasma warfarin level (P < 0.05) occurred with daily disulfiram compared with warfarin alone, for both the single-dose and 21-day experiments. In the single-dose and 21-day experiments a highly significant correlation of the changes in plasma warfarin levels and in the hypoprothrombinemia occurred, which was positive in 13 and negative in 2 experiments. We conclude that disulfiram increases the anticoagulant effect of warfarin therapy in most but not all subjects by inhibiting its metabolism in the liver. An augmentation of the therapeutic effect of a drug by disulfiram has thus been shown for the first time in humans.





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