MajorSystemic glucocorticoid×HIV protease inhibitor / pharmacokinetic booster
Updated · Methodology
Mechanism
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.
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 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.
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.
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Sources
- FDA: Norvir (ritonavir) prescribing information contraindications (2018)– ; DailyMed setid 2849298e-de6e-47bb-8194-56e075b33fc3
- AEMPS: Ficha técnica: Ritonavir (nº registro 81039), sección 4.5 (2025)– AEMPS, CIMA, nº registro 81039, sección 4.5
- AEMPS: Ficha técnica: Metilprednisolona (nº registro 71866), sección 4.5 (2024)– AEMPS, CIMA, nº registro 71866, revisión 11/2024, sección 4.5