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.

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.

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.

The impact of COVID-19 pandemic on colorectal cancer patients at an NHS Foundation Trust hospital-A retrospective cohort study.

INTRODUCTION: Current NHS guidelines recommend that treatment of colorectal patients referred through the two-week wait referral system should occur within sixty two days from the date of referral. The COVID-19 pandemic which started in March 2020 has however led to significant delays in the delivery of health services, including colorectal cancer treatments. This study investigates the effects of delayed colorectal cancer treatments during the COVID pandemic on disease progression. METHODS: A retrospective chart review of 107 patients with histologically confirmed diagnosis of colorectal cancer was conducted. The occurrence of cancer upstaging after initial diagnosis was assessed and compared between patients with treatment delays and patients who received treatments within the period recommended by NHS guidelines. A logistic regression was performed to evaluate the association between treatment delays beyond 62 days and cancer upstaging. RESULTS: The median age of the cohort was 71.2 years and 64.5% of the patients were over 65 years. Treatment delays were observed in 53.3% of reviewed patients. Patients with treatment delays received cancer treatments 95.8 (31.0) days on average after referral, compared to 46.3 (11.5) days in patients who experienced no treatment delays (p-value<0.0001). 38.6% of patients with treatment delays experienced cancer upstaging by the time of treatment, compared to 20% in the non-delay group (p-value = 0.036). Patients who received treatment after sixty two days from date of referral were 3.27 times more likely to experience colorectal cancer upstaging compared to those who received timely treatments. CONCLUSION: Although an effective response to the Covid-19 pandemic requires the reallocation of healthcare resources, there is a need to ensure that treatments and health outcomes of patients with chronic diseases such as colorectal cancer continue to be prioritized and delivered in timely fashion.