Major
Ketoconazole × methylprednisolone
Systemic antimycotics. Imidazole derivatives×Systemic glucocorticoid
Mechanism
Ketoconazole strongly blocks CYP3A4 – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 2- to 3-fold. Risk of iatrogenic Cushing's syndrome and adrenal insufficiency on withdrawal.
Symptoms
Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: adrenal insufficiency risk with hypotension and weakness.
Management
Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, halve the methylprednisolone dose.