Description
Fluconazole inhibits CYP3A4, reducing dexamethasone clearance and raising dexamethasone plasma levels, potentially causing Cushingoid features or adrenal suppression on steroid withdrawal.
Mechanism
Fluconazole's potent CYP3A4 and CYP2C19 inhibition reduces dexamethasone hepatic clearance, increasing systemic corticosteroid exposure and duration of action.
Clinical Significance
Case reports document iatrogenic Cushing syndrome in patients on dexamethasone who received fluconazole for fungal prophylaxis; the effect is more pronounced with higher dexamethasone doses or prolonged fluconazole use.
Management
Reduce dexamethasone dose when initiating fluconazole; monitor for Cushingoid symptoms (weight gain, moon face, hypertension, hyperglycaemia); consider alternative antifungal with less CYP3A4 inhibition (e.g., caspofungin).