Warfarin Bucolome

Bucolome increases the anticoagulant effects of warfarin by inhibiting its metabolism. 

A patient who had been taking warfarin with bucolome for 18 days developed gross haematuria. He was found to have an intraluminal ureteral haematoma and an excessively prolonged prothrombin time, and was treated with intravenous vitamin K." ... 

In vitro studies show that the bucolome can inhibit the metabolism of the more potent enantiomer 5-warfarin by the cytochrome P450 isoenzyme CYP2C9, thereby reducing its clearance and increasing its effects. ... 

Information appears to be limited to the reports cited here but the interaction would seem to be established and clinically important. Monitor the INR closely. A reduced warfarin dosage (the study cited above suggests a 30 to 60% reduction) is likely to be needed if both drugs are used concurrently to avoid excessive anticoagulation and possible bleeding. Note that bucolome is sometimes used with warfarin to enhance its therapeutic effect. Based on the mechanism of action, acenocoumarol and phenpro-coumon would be anticipated to be similarly affected. 

TakahashiH, Kashima T, Kimura S, MurataN, TakabaT, Iwade K, Abe T, Tainaka H, Yas-umori T, Echizen H. Pharmacokinetic interaction between warfarin and a uricosuric agent, bucolome application of in vitro approaches to piedictii in vivo reduction of ( ) warfarin clearance. DmgMetab Dispos (1999) 27, 1179-86. 

Matsumoto K, Ishida S, Ueno K, Hashimoto H, TakadaM, Tanaka K, Kamakura, Miyatake K, Shibakawa M. The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin. J Clin Pharmacol (2001) 41,459-64. 

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