Miconazole oral gel enhances acenocoumarol anticoagulant activity: A report of three cases

OBJECTIVE: To describe three cases of interaction between miconazole oral g el and acenocoumarol, manifested as an increase in the international normal ized ratio (INR). CASE SUMMARIES: Three patients (62-year-old woman, 89-year-old woman, 43-ye ar-old man) following oral antithrombotic treatment with acenocoumarol for different pathologies were diagnosed with oral candidiasis;and started mico nazole oral gel. In all cases, the previous INR values were repeatedly with in the therapeutic range. The following routine monitoring of the antithrom botic therapy showed a marked increase in anticoagulunt activity in all cas es, which returned to the therapeutic range after miconazole was withdrawn. None of the patients needed substantial changes in their habitual dosages of acenocoumarol in subsequent measurements of the INR to stay within the t herapeutic range. DISCUSSION: We report three cases in which a possible interaction between m iconazole oral gel and acenocoumarol is suggested by the chronological rela tionship between the introduction of miconazole and an increase in the INR. Miconazole exerts its fungistatic action by inhibiting some isoenzymes of the fungal cytochrome P450 system. Oral mucosa inflammation (as in oral can didiasis) may enhance its transmucosal absorption. In this setting, cytochr ome P450 isoenzymes belonging to the host may be inhibited too. This mechan ism provides an explanation for different interactions observed with micona zole oral gel. CONCLUSIONS: Miconazole oral gel enhances acenocoumarol anticoagulant activ ity. Although we did not observe major bleeding complications, we suggest t he use of other families of antifungal drugs, such as nystatin, to treat or al candidiasis in patients taking acenocoumarol.