methylprednisolone × ritonavir

Ritonavir is the most potent CYP3A4 inhibitor available – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 5- to 10-fold. High risk of iatrogenic Cushing's syndrome and severe adrenal insufficiency on withdrawal.

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: adrenal insufficiency risk with hypotension and weakness.

Avoid the combination. Alternative glucocorticoid: hydrocortisone (less CYP3A4-dependent) or inhaled/topical routes (no systemic effect). If methylprednisolone is needed, reduce 5-fold and keep the course as short as possible. Taper over several weeks on withdrawal because of suppressed adrenal cortex.