Drug interactions between Daktozin and Miradon

anisindione ↔ miconazole

Applies to:Miradon (anisindione) and Daktozin (miconazole/zinc oxide topical)

MONITOR CLOSELY: Systemically or even topically administered miconazole may increase the plasma concentrations and hypoprothrombinemic effect of warfarin. The proposed mechanism is miconazole inhibition of CYP450 2C9, the isoenzyme responsible for the metabolic clearance of the more active S(-) enantiomer of warfarin. There have been case reports of patients stabilized on warfarin who developed bleeding complications, bruising, and/or significantly increased prothrombin time (PT) or INR following the addition of miconazole. The interaction has also been reported with other oral anticoagulants and reportedly may occur up to 2 weeks after initiation of miconazole. Although the interaction is most likely to occur with systemic miconazole, it has been reported occasionally with oral gel and intravaginal formulations. In one case, a 52-year-old woman taking warfarin experienced hemorrhage of the right kidney after 12 days of using vaginal miconazole. Her PT and partial thromboplastin time were elevated upon hospitalization but returned to normal after discontinuation of miconazole use. There is also a reported case of an 80-year-old man stabilized on warfarin who developed a marked increase in his INR following application of a miconazole cream to his groin area for 2 weeks. Another 80-year-old man had a cerebral vascular accident following application of miconazole, although causality could not be established due to multiple medical problems and concurrent medications. A handful of cases involved oral miconazole gel, generally when it was applied to inflamed or compromised oral mucosa or when substantial amounts were swallowed following application, resulting in complications including epistaxis, spontaneous bruising, hematoma, hematuria, melena, and hypotension.

MANAGEMENT: Patients receiving warfarin or other oral anticoagulants should be closely monitored during concomitant therapy with miconazole. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation or discontinuation of miconazole therapy in patients who are stabilized on their anticoagulant regimen. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools. Although vaginally administered miconazole is generally less than 2% absorbed in healthy women of childbearing age, increased absorption may occur in the presence of atrophic vaginal epithelium. Therefore, the same precaution is applicable when vaginal formulations of miconazole is prescribed to women receiving oral anticoagulant therapy.