Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;43(12):1251-1261.
doi: 10.1002/phar.2860. Epub 2023 Aug 21.

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

Xuya Xiao  1   2 , Hemalkumar B Mehta  1   2 , Jill Curran  1   2 , Brian T Garibaldi  3 , G Caleb Alexander  1   2   4 ; National Covid Cohort Collaborative (N3C) Consortium
Collaborators, Affiliations

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

Xuya Xiao et al. Pharmacotherapy. 2023 Dec.

Abstract

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.

Keywords: SARS-CoV-2; antivirals; drug interactions; drug safety; nirmatrelvir/ritonavir; patient safety.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Dr. Alexander is past Chair and a current member of FDA’s Peripheral and Central Nervous System Advisory Committee; is a co-founding Principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation, for whom he has served as a paid expert witness; and is a past member of OptumRx’s National P&T Committee. Dr. Garibaldi is a member of the FDA Pulmonary-Asthma Drug Advisory Committee and has received consulting fees from Janssen Research and Development LLC, Gilead Sciences and Atea Pharmaceuticals. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies.

Figures

Figure 1.
Figure 1.
Study implementation
Figure 2.
Figure 2.
Study participants flow diagram.
Figure 3.
Figure 3.
Prevalence of most frequently prescribed co-medications among 521 individuals with potential moderate to severe DDIs
Figure 4.
Figure 4.
Adjusted association between risk factors and potential moderate to severe DDIs DDIs drug-drug interactions, OR odds ratio, 95%CI 95% confidence interval The p Value of rheumatic disease (p=0.115) was larger than 0.1 in univariable analysis and therefore not included in the multivariable model *p Value is less than 0.05
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention. COVID Data Tracker. Atlanta, GA: US Department of Health and Human Services, CDC; 2023, April 03. https://covid.cdc.gov/covid-data-tracker
    1. Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19 [Internet]. U.S.Food & Drug Administration; c2021[cited 2023 Mar 22]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19...
    1. Pfizer’s Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study [Internet]. Pfizer; c2021. [cited 2022 July 23]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizers-n....
    1. COVID-19 Treatment Guidelines [Internet]. National Institutes of Health; c2022. [cited 2022 May 29]. Available from: https://www.covid19treatmentguidelines.nih.gov/.
    1. COVID-19 Drug Interactions [Internet]. University of Liverpool; c2022. [cited 2022 May 10]. Available from: https://www.covid19-druginteractions.org/checker.

Publication types

Grants and funding