Potential Cyp3a4-Mediated Drug-Drug Interactions with Ritonavir-Containing Medications in U.S. Patients with Diabetes or Cardiovascular Diseases: An Analysis of Nhanes Data

This cross-sectional study examined the 2015-2019 National Health and Nutrition Examination Surveys (NHANES), which has been used in previous COVID-19 research, to estimate the proportion of adults with diabetes and serious heart conditions (SHCs) at risk of potential drug-drug interactions (pDDIs) arising from concomitant use of ritonavir and medications used to treat their comorbid conditions. Medications metabolized through the CYP3A4 pathway were identified as having pDDI with ritonavir, and were categorized as contraindicated, major, moderate, or minor pDDI severity using data sources from University of Liverpool, Lexicomp® and the FDA. Age-stratified prevalence of pDDIs were estimated using U.S. population weights (Table 1). 6.3% and 11.0% of survey participants reported a diagnosis of SHC and diabetes, respectively. pDDIs of any severity were identified in 44.5% of all adults; with 28.4% at risk of major or contraindicated pDDIs. Major or contraindicated pDDIs were observed in 58.1% of adults 60+. Among individuals with diabetes and SHCs, respectively, pDDIs were identified in 83.5% and 90.9% of all adults and in 92.1% and 95.5% of adults 60+. Major or contraindicated pDDIs were identified in 69.5% and 80.2% of adults with diabetes and SHC, respectively; and in 81.4% and 86.0% of individuals with diabetes and SHC aged 60+. This study suggests that majority of U.S. adults with diabetes or SHC are at risk of a major or contraindicated pDDI if treated with ritonavir-containing therapies. Findings highlight the importance of pDDI assessments in determining appropriate COVID-19 therapies, especially for multimorbid and elderly patients.