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.
Authors
- Fiona Marra (ORCID: https://orcid.org/0000-0003-1326-1149)
- Kimberly K. Scarsi (ORCID: https://orcid.org/0000-0001-9406-693X)
- Gregory Eschenauer (ORCID: https://orcid.org/0000-0001-5971-0531)
- Jennifer Cocohoba (ORCID: https://orcid.org/0000-0003-4003-1939)
- Pierre Giguère (ORCID: https://orcid.org/0000-0003-1174-8965)
- Page Crew (ORCID: https://orcid.org/0000-0003-2803-4264)
- Kimberly Struble (ORCID: https://orcid.org/0000-0001-9618-0875)
- Saye Khoo (ORCID: https://orcid.org/0000-0002-2769-0967)
- Melissa E. Badowski (ORCID: https://orcid.org/0000-0001-7564-0131)
- Safia Kuriakose (ORCID: https://orcid.org/0009-0001-4076-6276)
- Catia Marzolini (ORCID: https://orcid.org/0000-0002-2312-7050)
- Alice K. Pau (ORCID: https://orcid.org/0000-0002-0153-0236)
- Claire Lund (ORCID: https://orcid.org/0009-0006-2338-810X)
- Tessa Senneker (ORCID: https://orcid.org/0009-0006-6275-5988)
- Deborah Yoong
- Pamela S. Belperio (ORCID: https://orcid.org/0000-0002-6435-7450)
- Sarita D. Boyd (ORCID: https://orcid.org/0000-0002-5859-7722)
- Alice Tseng (ORCID: https://orcid.org/0000-0002-6480-6690)
- Salin Nhean (ORCID: https://orcid.org/0000-0001-6310-2811)
- Alison Boyle (ORCID: https://orcid.org/0000-0003-1365-9755)
- Jomy George
- Sara Gibbons
- Justin Chiong (ORCID: https://orcid.org/0000-0001-8063-6399)
Institutions
- National Institutes of Health (US)
- Nebraska Medical Center (US)
- United States Food and Drug Administration (US)
- University Health Network (CA)
- Center for Drug Evaluation and Research (US)
- University of Liverpool (GB)
- University of Michigan (US)
- University Hospital of Basel (CH)
- Department of Human Services (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
- Kingston Health Sciences Centre (CA)
- VA Greater Los Angeles Healthcare System (US)
- University of Nebraska Medical Center (US)
- ICF International (United States) (US)
- University of Lausanne (CH)
Publication Details
- Journal
- Clinical Infectious Diseases
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1093/cid/ciaf606
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00