Potential Drug-Drug Interactions Among U.S. Adults Treated With Nirmatrelvir/Ritonavir (Paxlovid): A Cross-sectional Study Of The National COVID Cohort Collaborative (N3C)
Importance. Nirmatrelvir/ritonavir has potential to interact with many drugs. 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, Setting, and Participants. Cross-sectional study using electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID-19 data resources in the US. Study participants were outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022. Main Outcome and Measures. Potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after receiving nirmatrelvir/ritonavir. 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), with a history of solid organ transplant (OR 3.63, CI 2.05-6.45). Conclusions and Relevance. 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. Key words: Drug interactions; drug safety; SARS-CoV-2; antivirals; patient safety; nirmatrelvir/ritonavir
