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Background: In the UK, a regional vertical system for the delivery of COVID-19 medicines has been in place. This enabled centralization of expertise in risk stratification of patients, and in understanding and mitigating drug–drug interactions. Research design and methods: We analyzed real-world drug–drug interactions in adult patients referred for nirmatrelvir/ritonavir therapy across one such geographic area covering 2.2 million London citizens. Results: Among 208 who received NMV/r therapy, we identified 184 potential DDIs, 8% precluded nirmatrelvir/ritonavir use, 53% required management, but 56% of these did not have documented advice to hold therapy. Conclusions: This highlights the need to maintain and develop pathways for clinical pharmacology expertise in COVID-19 management. [ABSTRACT FROM AUTHOR]