Miconazole Acenocoumarol

Interactions between conmarins and miconazole have been reported, although the mechanism of the interaction is not known. There have been two separate reports of potentiation of the anticoagulant effect of acenocoumarol by non-systemic administration of miconazole. Three patients taking long-term acenocoumarol who used miconazole gel for oral candidiasis had significant rises in INR (197). In two other patients vaginal miconazole potentiated the anticoagulant effect of acenocoumarol (198). 

Lansdorp D, Bressers HP, Dekens-Konter JA, Meyboom RH. Potentiation of acenocoumarol during vaginal administration of miconazole. Br J Clin Pharmacol 1999 47(2) 225-6. 

Marotel C, Cerisay D, Vasseur P, Rouvier B, Chabanne JP. Potentialisation des effets de I acenocou-marol par le gel buccal de miconazole. [Potentiation of the effects of acenocoumarol by a buccal gel of miconazole.] Presse Med 1986 15(33) 1684-5. 

Ortin M, Olalla JI, Muruzabal MJ, Peralta FG, Gutierrez MA. Miconazole oral gel enhances acenocoumarol anticoagulant activity a report of three cases. Ann Pharmacother 1999 33(2) 175-7. 

In rate, ketoconazole potentiated the anticoagulant eflect of acenocoumarol, but at much higher doses than miconazole , (p.388). It is now known that ketoconazole is an inhibitor of the cytochrome P450 isoenzyme CYP3A4, but this isoenzyme has only a minor role in the metabolism of warfarin (p.358), specifically the less active R-isomer. 

A few similar cases have also been reported for acenocoumarol " or fluindione with miconazole oral gel. In addition, in one cohort study in patients taking acenocoumarol or phenprocoumon, use of oral miconazole (form and doses not stated) markedly increased the risk of over-anti-coagulation (INR greater than 6 adjusted relative risk 36.6 range 12.4 to 108). When analysed separately, the adjusted relative risk was higher for acenocoumarol than phenprocoumon (35.1 versus 16.5). ... 

The Centres de Pharmacovigilance Hospitaliere in Bordeaux have on record 5 cases where miconazole (oral doses of 500 mg daily, where stated form not mentioned) was responsible for a marked increase in prothrombin times and/or bleeding (haematomas, haematuria, gastrointestinal bleeding) in patients taking acenocoumarol (2 cases), ethyl biscoumacetate (1 case), tioclomarol (1 case) and phenindione (1 case). Other cases and reports of this interaction involving acenocoumarol have been described elsewhere. " ... 

Ponge T, Barrier J, Spreux A, Giidlou B, Larousse C, Grolleau JY. Potentialisation des effets de I acenocoumarol par le miconazole. Therapie (1982) 37,221-2. 

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