Prevalence of Potential Drug-drug Interactions With Ritonavir-containing COVID-19 Therapy in the United States: An Analysis of the National Health and Nutrition Examination Survey.

PURPOSE: The evolving epidemiology and treatment landscape of COVID-19 necessitates research into potential drug-drug interactions (pDDIs) from the use of new treatments for COVID-19, particularly those that contain ritonavir, a potent inhibitor of the cytochrome P350 3A4 (CYP3A4) metabolic pathway. In this study, we assessed the prevalence of pDDIs between medications for chronic conditions metabolized through the CYP3A4 metabolic pathway and ritonavir-containing COVID-19 medications in the US general population. METHODS: This study combined National Health and Nutrition Examination Survey (NHANES) waves 2015 to 2016 and 2017 to March 2020 to observe pDDI prevalence between ritonavir-containing therapy and coadministered medications among US adults 18 years or older. CYP3A4-mediated medications were identified from affirmative medication questionnaire response and associated prescription examination by surveyors. CYP3A4-mediated medications with associated pDDIs with ritonavir and assessed pDDI severity (minor, major, moderate, and severe) were obtained from the University of Liverpool's COVID-19 online drug interaction checker, Lexicomp, and US Food and Drug Administration fact sheets. pDDI prevalence and severity were evaluated by demographic characteristics and COVID-19 risk factors. FINDINGS: A total of 15,685 adult participants were identified during the 2015 to 2020 NHANES waves. Survey participants used a mean (SD) of 2.7 (1.8) drugs with likelihood of a pDDI. The weighted prevalence of major to contraindicated pDDIs among the US population was 29.3%. Prevalence rates among those 60 years and older, with serious heart conditions, with moderate chronic kidney disease (CKD), with severe CKD, with diabetes, and with HIV were 60.2%, 80.7%, 73.9%, 69.5%, 63.4%, and 68.5%, respectively. Results remained largely unchanged after removal of statins from the list of drugs associated with ritonavir-based pDDIs. IMPLICATIONS: Approximately one-third of the US population would be at risk for a major or contraindicated pDDI should they receive a ritonavir-containing regimen, and this risk increases significantly among individuals 60 years or older and with comorbidities such as serious heart conditions, CKD, diabetes, and HIV. The state of polypharmacy in the US population and the quickly changing COVID-19 landscape indicate significant risk of pDDIs among those requiring treatment with ritonavir-containing COVID-19 medications. Practitioners should take polypharmacy, age, and comorbidity profile into account when prescribing COVID-19 therapies. Alternative treatment regimens should be considered, especially for those of older age and those with risk factors for progression to severe COVID-19.

Prevalence of Potential Drug-Drug Interactions with Ritonavir-Containing COVID-19 therapy in the United States: An Analysis of the National Health and Nutrition Examination Survey

Purpose The evolving epidemiology and treatment landscape of coronavirus disease 2019 (COVID-19) necessitates research into potential drug-drug interactions (pDDIs) from the use of new treatments for COVID-19, particularly those which contain ritonavir, a potent inhibitor of the cytochrome P350 3A4 (CYP3A4) metabolic pathway. In this study we assessed the prevalence of pDDIs between chronic condition medications metabolized through the CYP3A4 metabolic pathway and ritonavir-containing COVID-19 medications in the US general population. Methods This study combined NHANES waves 2015-2016 and 2017-March 2020 to observe pDDI prevalence between ritonavir-containing therapy and co-administered medications among US adults aged 18 years or older. CYP3A4-mediated medications were identified from affirmative medication questionnaire response and associated prescription examination by surveyors. CYP3A4-mediated medications with associated pDDIs with ritonavir and assessed pDDI severity (minor, major, moderate, and severe) was obtained from the University of Liverpool's Drug-Drug Interaction Checker, Lexicomp, and FDA fact sheets. pDDI prevalence and severity were evaluated by demographics and COVID-19 risk factors. Findings 15,685 adult participants were identified during the 2015-2020 NHANES waves. Survey participants used an average of 2.7 (SD=1.8) drugs with likelihood of a pDDI. The weighted prevalence of major to contraindicated pDDIs among the US population was 29.3%. Prevalence among those with age 60 years and older, serious heart conditions, moderate CKD, severe CKD, diabetes, and HIV was 60.2%, 80.7%, 73.9%, 69.5%, 63.4%, and 68.5%, respectively. Results remained largely unchanged after removal of statins from the list of drugs associated with ritonavir-based pDDIs. Implications Approximately one-third of the US population would be at risk of a major or contraindicated pDDI should they receive a ritonavir-containing regimen, and this risk increases significantly among individuals aged 60 years or older and with comorbidities such as serious heart conditions, CKD, diabetes, and HIV. The state of polypharmacy in the US population and the quickly changing COVID-19 landscape indicates significant risk of pDDIs among those requiring treatment with ritonavir-containing COVID-19 medications. Providers should take polypharmacy, age and comorbidity profile into account when prescribing COVID-19 therapies. Alternative treatment regimens should be considered, especially for those of older age and those with risk factors for progression to severe COVID-19.

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.