Major
Budesonide × Clarithromycin
Inhaled corticosteroids (ICS)×Macrolide antibiotic
Mechanism
Clarithromycin blocks CYP3A4 – the main hepatic metabolic route for budesonide. Systemic budesonide exposure (oral or inhaled) rises 4- to 8-fold. Cushing's syndrome and adrenal insufficiency have been reported.
Symptoms
Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: risk of adrenal insufficiency with hypotension and weakness.
Management
For short clarithromycin courses (5–7 days), halve budesonide temporarily. For prolonged therapy, switch antibiotics (azithromycin, doxycycline) or replace budesonide with fluticasone/mometasone (less CYP3A4-dependent).