ArticleClinical and translational science2026
Managing High-Risk Drug Interactions With Nirmatrelvir/Ritonavir: Experience From a Dedicated Pharmacology Advice Service.
Article in Clinical and translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Nirmatrelvir boosted with ritonavir is a key antiviral against COVID-19, yet ritonavir's potent CYP3A4 inhibition exposes patients to numerous drug-drug interactions. To make prescribing safer, a national proactive system providing expert pharmacology advice was implemented in France. This retrospective study reports the experience of the pharmacology department at Rennes University Hospital, which provided these expert services from February 2022 to December 2024. We evaluated 455 consecutive patients (median age 75 years, median eight co-medications per patient, 3813 prescription lines). Nirmatrelvir/ritonavir was ultimately contra indicated in 26 patients. Among the 429 eligible patients (3582 prescription lines), 86.7% (372/429) had at least one clinically relevant drug interaction; 60.8% (261/429) had ≥ 2; 30.4% (130/429) had ≥ 3. Among the 831 interacting medication lines, the main drug classes involved: statins (17.7%, 147/831), immunosuppressants (12.0%, 100/831), and direct oral anticoagulants (10.5%, 87/831), with the drug mix evolving over time from transplant-related immunosuppressants in 2022 to statin agents in 2023-2024. Expert review identified options to navigate initial contraindications in 13.5% (58/429) of patients. Despite a very high prevalence of potential clinically relevant DDIs, the service supported prescribers' decision-making to consider nirmatrelvir/ritonavir in most evaluated patients, primarily via conservative co-medication management: continue unchanged 77.2% (2764/3582), temporary interruption 13.8% (493/3582), dose adjustment 5.8% (208/3582), alternative therapy (117/3582); and via targeted monitoring: clinical monitoring 45.9% (197/429) and therapeutic drug monitoring 14.2% (61/429). As a retrospective service evaluation, these findings are hypothesis-generating and emphasize a scalable model of proactive clinical pharmacology support to secure interaction-prone therapies in aging, polymedicated populations.
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