A 62-year-old diabetic man tests positive for SARS-CoV-2, is symptomatic on day 4, and has risk factors for progression. Nirmatrelvir-ritonavir is being considered. His regular medications include simvastatin, amlodipine, and metformin. Which adjustment is required?

• A Metformin must be stopped because ritonavir causes fatal lactic acidosis
• B Simvastatin must be held during the 5-day course because ritonavir strongly inhibits CYP3A4 ✓
• C Amlodipine must be doubled because ritonavir induces its metabolism
• D No changes are needed since nirmatrelvir-ritonavir has no significant interactions

Explanation

Ritonavir is a potent CYP3B4 inhibitor, so coadministration with simvastatin greatly raises statin levels and risks rhabdomyolysis; the statin should be paused for the course and restarted afterwards. Metformin has no relevant interaction, and amlodipine levels may rise modestly rather than fall, so dose reduction rather than doubling is considered if needed. Recognising CYP3B4-mediated interactions is essential before prescribing this antiviral.

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

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