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

## TL;DR

Experts from multiple countries worked together to create clear drug interaction guidelines for a new coronavirus treatment, improving prescribing during the pandemic.

## Contribution

A collaborative framework for harmonizing drug interaction guidance for nirmatrelvir/ritonavir was developed during the pandemic.

## Key findings

- A unified approach to managing drug interactions with nirmatrelvir/ritonavir was created through international collaboration.
- The LiON-PK collaboration provided practical guidance to reduce prescriber uncertainty during the pandemic.
- The framework can inform future pandemic preparedness and complex medication management.

## Abstract

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.

In December 2021, the National Institutes of Health panel on coronavirus disease 2019 treatment guidelines, the Ontario Science Table, and the University of Liverpool collaborated to harmonize drug interaction guidance for nirmatrelvir/ritonavir. This article outlines the processes and lessons learned from this collaboration to inform future pandemic preparedness.