International Collaboration to Develop and Harmonize Drug Interaction Guidance for Nirmatrelvir/Ritonavir During COVID-19: Lessons Learned for Future Pandemic Preparedness.

In December 2021 and January 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug, nirmatrelvir/ritonavir, was authorized in the United States, Canada, and Europe. However, ritonavir has significant drug-drug interaction (DDI) potential, and information resources were incomplete or provided conflicting advice for certain DDIs. Within the challenging pandemic setting, nirmatrelvir/ritonavir was being prescribed largely by clinicians unfamiliar with ritonavir. Coronavirus disease 2019 (COVID-19) affects people with comorbid conditions and polypharmacy who could benefit from therapy, but prescriber uncertainty surrounding the appropriate management of DDIs was a barrier to the use of nirmatrelvir/ritonavir. To support clinicians, the National Institutes of Health (NIH) panel on COVID-19 guidelines, the Ontario COVID-19 Science Advisory Table, and the University of Liverpool independently developed prescribing guidelines. Ultimately, the groups united to establish the LiON-PK (Liverpool-Ontario-NIH Pharmacokinetics) collaboration. Here we describe how the team developed pragmatic and harmonized guidance for managing DDIs with nirmatrelvir/ritonavir. This framework may inform development of prescribing resources for other complex medications or for future pandemic preparedness.