Potential drug–drug interactions among U.S. adults treated with nirmatrelvir/ritonavir: A cross‐sectional study of the National Covid Cohort Collaborative (N3C)

Study Objective To estimate the prevalence of potential moderate to severe drug–drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs. Design Cross‐sectional study. Data Source Electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID‐19 data resources in the United States. Patients Outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022. Intervention Nirmatrelvir/ritonavir. Measurements The outcome is potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir. Main Results Of 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8 ± 17.1 years, 39.5% were male, and 65.8% were non‐Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10‐year increase, 95% confidence interval [CI] 1.08–1.25), male (OR 1.36, CI 1.09–1.71), smokers (OR 1.38, CI 1.10–1.73), on more co‐medications (OR 1.35, CI 1.31–1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05–6.45). Conclusions One in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks.