A 66-year-old man with type 2 diabetes develops mild COVID-19 within 3 days of symptom onset. He takes metformin and simvastatin 40 mg daily. Nirmatrelvir-ritonavir is being considered. What is the main pharmacological concern?

• A Metformin increases nirmatrelvir levels causing lactic acidosis
• B Simvastatin antagonises the viral main protease, reducing efficacy
• C Ritonavir inhibits CYP3A4, causing dangerous accumulation of simvastatin ✓
• D Nirmatrelvir causes severe hypoglycaemia when combined with statins

Explanation

Ritonavir is a potent CYP3A4 inhibitor included solely to boost nirmatrelvir plasma concentrations. Co-administration with simvastatin markedly raises statin levels, risking rhabdomyolysis, so simvastatin must be withheld during the 5-day course. Metformin needs no dose change, statins do not interfere with the viral protease target, and there is no hypoglycaemic interaction. Recognising CYP3A-mediated interactions is the key prescribing skill for this drug.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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