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.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.