Ortín M, Olalla J I, Muruzábal M J, Peralta F G, Gutiérrez M A
Department of Hematology, Hospital Sierrallana, Torrelavega, Cantabria, Spain.
Ann Pharmacother. 1999 Feb;33(2):175-7. doi: 10.1345/aph.18011.
To describe three cases of interaction between miconazole oral gel and acenocoumarol, manifested as an increase in the international normalized ratio (INR).
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a marked increase in anticoagulant activity in all cases, which returned to the therapeutic range after miconazole was withdrawn.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.
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.
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.
描述3例咪康唑口腔凝胶与醋硝香豆素相互作用的病例，表现为国际标准化比值（INR）升高。
3例患者（62岁女性、89岁女性、43岁男性）因不同疾病接受醋硝香豆素口服抗血栓治疗，被诊断为口腔念珠菌病并开始使用咪康唑口腔凝胶。在所有病例中，之前的INR值多次处于治疗范围内。随后对抗血栓治疗的常规监测显示，所有病例的抗凝活性均显著升高，停用咪康唑后恢复至治疗范围。在随后的INR测量中，为使INR保持在治疗范围内，所有患者在其习惯性醋硝香豆素剂量方面均无需大幅调整。
我们报告3例病例，咪康唑的引入与INR升高之间的时间关系提示咪康唑口腔凝胶与醋硝香豆素之间可能存在相互作用。咪康唑通过抑制真菌细胞色素P450系统的一些同工酶发挥其抑菌作用。口腔黏膜炎症（如口腔念珠菌病）可能会增强其经黏膜吸收。在这种情况下，宿主的细胞色素P450同工酶也可能被抑制。这一机制为观察到的咪康唑口腔凝胶的不同相互作用提供了解释。
咪康唑口腔凝胶可增强醋硝香豆素的抗凝活性。尽管我们未观察到严重出血并发症，但我们建议使用其他抗真菌药物类别，如制霉菌素，来治疗服用醋硝香豆素患者的口腔念珠菌病。
