Large doses of drugs that are highly bound to proteins can displace coumarin anticoagulants from plasma proteins and thereby potentiate anticoagulation. Mefenamic acid, ethacrynic acid, nalidixoic acid, and diazoxide displace significant amounts of warfarin from human albumin in vitro by a noncompetitive mechanism. The relative potency of these displacing agents is: mefenamic acid > ethacrynic acid > diazoxide > nalidixic acid. If this effect occw's in vivo, clinical use of these drugs would cause an increase of 66 to 400 per cent in free active warfarin and make it necessary to reduce anticoagulant dosage in order to prevent excessive hypoprothrombinemia and hemorrhage.
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Sellers et al. (1970) studied this question.