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.

BACKGROUND: Patients with COVID-19 receiving ritonavir-containing therapies are at risk of potential drug-drug interactions (pDDIs) because of ritonavir's effects on cytochrome P450 3A4. OBJECTIVE: To assess the prevalence of pDDIs with ritonavir-containing COVID-19 therapy in adults with COVID-19 using the Optum Clinformatics Data Mart database. METHODS: In this retrospective, observational cohort study, patients with COVID-19 aged 18 years or older prescribed cytochrome P450 3A4-mediated medications with supply days overlapping the date of COVID-19 diagnosis between January 1, 2020, and June 30, 2021, were classified as having pDDIs. pDDI was classified as contraindicated, major, moderate, or mild using established drug interaction resources. Prevalence of pDDIs with ritonavir-containing COVID-19 therapy was estimated for the entire cohort and in patient groups with high risk of severe COVID-19 progression or pDDIs. Actual COVID-19 treatments received by the patients, if any, were not considered. Outcomes were presented descriptively without adjusted comparisons. RESULTS: A total of 718,387 patients with COVID-19 were identified. The age-sex standardized national prevalence of pDDIs of any severity was estimated at 52.2%. Approximately 34.5% were at risk of contraindicated or major pDDIs. Compared with patients without pDDI, patients exposed to pDDIs were older and more likely to be female, reside in long-term care facilities, and have risk factors for progression to severe COVID-19. Higher prevalence of major/contraindicated pDDIs was observed in older patients (76.1%), female patients (65.0%), and patients with multiple morbidities (84.6%). CONCLUSIONS: Study findings demonstrate that more than one-third of patients with COVID-19 were at risk of significant pDDIs if treated with ritonavir-containing COVID-19 therapy and highlight the need to assess all patients with COVID-19 for pDDIs. Ritonavir-based therapies may not be appropriate for certain patient groups, and alternative therapies should be considered. DISCLOSURES: Drs Igho-Osagie, Puenpatom, and Grifasi Williams are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Dr Song and Ms He are employees of Analysis Group, Inc., and served as paid consultants for Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Drs Yi and Wang, and Mr Berman, and Ms Gu were employees of Analysis Group, Inc., at the time of study conduct. Financial support for this study was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Short-Term Tea Consumption Is Not Associated with a Reduction in Blood Lipids or Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: A recent systematic review of epidemiological evidence suggests that higher amounts of tea intake are associated with lower risks of cardiovascular disease (CVD) incidence and mortality. OBJECTIVES: Our study objective was to assess mechanisms by which tea consumption may influence CVD risks. METHODS: A systematic review and meta-analysis was conducted to investigate the effects of green and/or black tea consumption (≥4 wk) on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride (TG) in healthy populations and among at-risk adults (analyzed separately) with metabolic syndrome, prediabetes, and hypercholesterolemia. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the strength of evidence (SoE). RESULTS: A total of 14 unique RCTs which randomly assigned 798 participants to either green tea, black tea, or placebo controls were included in our analyses. Intervention durations ranged from 4 to 24 wk (mean: 7.4 wk). Individual studies were judged as moderate to high quality based on risk of bias assessments. SoE was low to moderate owing to low sample sizes and insufficient power for most included studies to observe changes in the measured CVD biomarkers. Meta-analyses showed no significant effects of tea consumption on SBP, DBP, total cholesterol, LDL cholesterol, HDL cholesterol, and TG in healthy and at-risk adults (i.e., adults with obesity, prediabetes, borderline hypercholesterolemia, and metabolic syndrome). CONCLUSIONS: Short-term (4-24 wk) tea consumption does not appear to significantly affect blood pressure or lipids in healthy or at-risk adults, although the evidence is limited by insufficient power to detect changes in these CVD biomarkers. High-quality RCTs with longer durations and sufficient sample sizes are needed to fully elucidate the effects of tea. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020134513.