Interaction between Chloral Hydrate and Warfarin

Data from a comprehensive drug surveillance program were analyzed to determine the clinical importance of the interaction between chloral hydrate and the oral anticoagulant warfarin. Patients anticoagulated during hospitalization were divided into three groups receiving continuous, occasional or no chloral hydrate during the first four days of warfarin therapy. Those receiving continuous chloral hydrate therapy required significantly less warfarin (p <0.01) during the induction phase of anticoagulation than those receiving no chloral hydrate. Patients given occasional chloral hydrate required an intermediate dose. All patients received similar loading doses of warfarin and similar doses from the fifth day onward. The results indicate that the interaction between these drugs is of clinical importance and that care should be exercised when they are administered concurrently. SELLERS and Koch-Weser¹ have recently demonstrated that trichloroacetic acid, a major metabolite of chloral hydrate, displaces warfarin from its binding sites on plasma albumin. This action temporarily raises plasma levels of unbound warfarin and thus increases the pharmacologic effect per unit dose. In their studies, Sellers and Koch-Weser also demonstrated that increased plasma levels of unbound warfarin are associated with a decrease in the plasma half-life of the drug. Griner et al.² and Udall³ studied the potential interaction of warfarin and chloral hydrate in a clinical setting and failed to show an increased prothrombin time in patients given warfarin and.