Interaction of miconazole oral gel with warfarin and cyclosporine in a patient with nephrotic syndrome.

It is well known that miconazole inhibits cytochrome P450 (CYP). However, this drug in oral gel form is believed not to absorb into systemic circulation, and therefore not to inhibit CYP. We experienced a case of increased oral bioavailability of warfarin and cyclosporine with this gel for treatment of oral candidiasis in a patient with nephrotic syndrome. Her prothrombin time-international normalized ratio (PT-INR) increased from 2 to 7.25, and the cyclosporine concentration at 2 h after final dosing (C2) increased from 633.8 to 1396.5 ng/ml 6 days after the coadministration. These problems were resolved by termination of the gel and switching to amphotericin B gargle. We further detected a significant amount of miconazole in her plasma, directly showing for the first time in a patient with this interaction that oral miconazole gel was actually absorbed into systemic circulation. Because warfarin and cyclosporine are often used simultaneously by nephrologists, caution should be applied with combined use of these drugs and oral miconazole gel to avoid adverse reaction.