Commonly used drugs such as mefenamic acid and diazepam should be administered with caution in patients on warfarin therapy due to the risk of drug interactions leading to severe bleeding.
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May signal bleeding risk with warfarin plus mefenamic acid or diazepam; hypothesis-generating and requires controlled confirmation.
Following a marked hypoprothrombinemia, unexpected hematuria occured in a 67-year-old woman taking a maintenance dose of warfarin. Diazepam and tipepidine given concomitantly were suspected to have a responsibility for the hypoprothrombinemia. Tipepidine did not show any effect on the prothrombin time in a healthy volunteer who was administered warfarin.A possible mechanism in protein binding competetion of diazepam with warfarin still remains in question, although a few reports have mentioned that diazepam did not influence on the metabolism of warfarin in man and animals. The second case was a 56-year-old man who was admitted to the hospital under the diagnosis of myocardial infarction.In this case melena developed after giving of mefenamic acid concurrently with warfarin. It has been clarified that mefenamic acid could displace warfarin from its binding site of albumin and enhance the effect of warfarin. It is concluded that these drugs which are commonly used should be given carefully to the patients on warfarin therapy.
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Tsutsumi et al. (1975) studied this question.
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