Potential drug-drug interactions in hospitalized COVID-19 patients (CATCO-DDI)

ABSTRACT

Background: Therapies for managing COVID-19 disease may interact with other drugs, particularly in hospitalized patients with comorbidities. Objectives: Characterize the prevalence of drug-drug interactions (DDIs) between investigational/approved medications for managing COVID-19 (COVID-meds) and co-medications (co-meds) in hospitalized COVID-19 patients. Methods: Multicentre retrospective observational study of hospitalized COVID-19 patients screened for the CATCO trial between 1-Apr-20 and 15-Sep-20. Patients' co-meds were assessed for potential DDIs with the following COVID-meds hydroxychloroquine (HQ), lopinavir/ritonavir (LPV), remdesivir (REM), dexamethasone (DEX), azithromycin (AZ), interferon beta-1B (IFN) and tocilizumab (TOC). The Liverpool-COVID DDI website and Lexicomp were used to identify and characterize DDI severity (red do not co-administer, amber potential interaction) and potential clinical impact. QT prolongation risk was assessed with the Tisdale risk score. The primary outcome was the prevalence of subjects with =1 potential clinically significant (red/amber) DDI between each COVID-med and co-med. Secondary outcomes included DDI severity and potential clinical impact. Descriptive statistics are presented as medians (range) or proportions. Results: Data from 51 patients are available 61% male, age 74 (44-95) years, 6 (1-15) comorbidities, Tisdale risk score 6 (31.4% moderate risk, 11.8% high risk) and 10 (0-19) co-meds. LPV had the highest rate of potential DDIs (92.2%, 45% red, 3 DDIs per patient) with risk of increased co-med toxicity (most commonly psychotropics, anticoagulants/antiplatelets), while REM and IFN had the least (2% and 9.6%, respectively). Most patients (75%) had =1 DEX DDI (mostly amber, 1per patient) with risk of increased co-med toxicity. The most common DDIs with HQ and AZ involved increased risk of QTc prolongation. Over one-third (35%) of patients were deemed ineligible for CATCO at screening due to DDIs with LPV. Conclusions: Hospitalized COVID-19 patients are at high risk of DDIs with many investigational/approved COVID medications. Routine DDI screening is recommended, ideally using both general and COVID-specific DDI resources.