Warfarin Cloral hydrate

The anticoagulant effects of warfarin are increased in the first few days of cloral hydrate use, but this is normally of little or no clinical importance. Cloral betaine and triclofos may be expected to behave similar. ... 

In a retrospective study in patients just starting warfarin, the same loading doses of warfarin were given to 32 patients taking cloral hydrate daily and 67 patient who did not receive cloral hydrate. The warfarin requirements of the cloral group during the first 4 days fell by about one-third, but rose again to control requirements by the fifth day. ... 

In a study in 8 subjects, the concurrent use of warfarin (loading dose 25 mg then 5 mg daily for 5 days) and cloral hydrate 1 g each night resulted in potentiation of the effect of warfarin, when compared with placebo (increase in prothrombin time of about 3 to 4 seconds). However, in a longer term study, the addition of cloral hydrate 500 mg at night for 4 weeks to subjects stabilised on warfarin did not alter the average prothrombin time before, during, and after the cloral treatment (18.9, 19.3, and 19.2 seconds, respectively). ... 

Similar results have been described in other studies in patients taking warfarin and cloral hydrate or triclofos. Qoral betaine appears to behave similarly. An isolated and by no means fully explained case of fatal hypoprothrombinaemia occurred in a patient taking dicoumarol who was given cloral hydrate for 10 days, later replaced by secobarbital." Another patient taking dicoumarol had a reduction in prothrombin times when given cloral hydrate."... 

Cloral hydrate is mainly metabolised to trichloroacetic acid, which then successfully competes with warfarin for its binding sites on plasma proteins. As a result, free and active molecules of warfarin are displaced into the plasma water and the effects of the warfarin are increased. But this is... 

The interaction between warfarin and cloral hydrate is well documented and well understood, but normally of little or no clinical importance. There is very good evidence that concurrent use need not be avoided. " However, it may be prudent to keep an eye on the anticoagulant response during the first 4 to 5 days, just to make sure it does not become excessive. It is not certain whether other anticoagulants behave in the same way because the evidence is sparse, indirect and inconclusive, but what is known suggests that the coumarins probably do. Triclofos and cloral betaine appear to behave like cloral hydrate. Dichloralphenazone on the other hand interacts quite diflerently (see Coumarins+Dichloralphenazone , p.399). 

The phenazone , (p.434) component of dichloralphenazone is a potent liver enzyme inducer, which increases the metabolism and clearance of the warfarin, thereby reducing its effects. The effects of the cloral hydrate , (p.396) component appear to be minimal. 

There is in vitro evidence that the serum binding of warfarin is decreased by sodium valproate so that free warfarin levels rise, by 32% according to one study. The increase in free warfarin levels is transient until a new equilibrium is reached, but theoretically could result in a transient increase in INR, as is seen with cloral hydrate , (p.396). 

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