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

OBJECTIVE: To describe three cases of interaction between miconazole oral gel and acenocoumarol, manifested as an increase in the international normalized ratio (INR). CASE SUMMARIES: Three patients (62-year-old woman, 89-year-old woman, 43-year-old man) following oral antithrombotic treatment with acenocoumarol for different pathologies were diagnosed with oral candidiasis and started miconazole oral gel. In all cases, the previous INR values were repeatedly within the therapeutic range. The following routine monitoring of the antithrombotic therapy showed a marked increase in anticoagulant activity in all cases, which returned to the therapeutic range after miconazole was withdrawn.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 therapeutic range. DISCUSSION: We report three cases in which a possible interaction between miconazole oral gel and acenocoumarol is suggested by the chronological relationship 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 candidiasis) may enhance its transmucosal absorption. In this setting, cytochrome P450 isoenzymes belonging to the host may be inhibited too. This mechanism provides an explanation for different interactions observed with miconazole oral gel. CONCLUSIONS: Miconazole oral gel enhances acenocoumarol anticoagulant activity. Although we did not observe major bleeding complications, we suggest the use of other families of antifungal drugs, such as nystatin, to treat oral candidiasis in patients taking acenocoumarol.