Major
Clarithromycin × methylprednisolone
Macrolide antibiotic×Systemic glucocorticoid
Mechanism
Clarithromycin blocks CYP3A4 – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 2- to 3-fold, with risk of iatrogenic Cushing's syndrome and hyperglycaemia.
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
For short clarithromycin courses (5–7 days), halve methylprednisolone temporarily. For prolonged therapy, switch antibiotics (azithromycin, doxycycline) or replace methylprednisolone with hydrocortisone (less CYP3A4-dependent).