Potential drug-drug interactions in a multi-center study of death cases of COVID-19: The significance of appropriate drug choice.

Objectives: The prevalence, types, severity, risk ratings, and common pairs of involved drugs, and the most important potential drug-drug interactions (pDDIs) in coronavirus disease 2019 (-COVID-19) deceased cases were evaluated.

Materials And Methods: We reviewed the medical records of 157 confirmed COVID-19 deceased cases hospitalized in 27 province-wide hospitals. Patients' demographics and clinical data (including comorbidities, vital signs, length of in-hospital survival, electrocardiograms (ECGs), medications, and lab test results) were extracted. The online Lexi-interact database and Stockley's drug interactions reference were used to detect pDDIs retrospectively. The QTc interval and total Tisdale risk score were also calculated. Descriptive analysis, analysis of variance, Fisher exact test, and multivariate analysis were conducted for data analysis.

Results: Of 157 study cases, 63% were male, had a mean age of 68 years, and 55.7% had one or more underlying diseases. All patients had polypharmacy, with 69.2% having ≥ 15 drugs/day. We detected 2,416 pDDIs in patients' records, of which 658 (27.2%) were interactions with COVID drugs. Lopinavir/ritonavir among -COVID drugs and fentanyl among non-COVID drugs were commonly involved in the interactions. pDDIs was significantly higher in the polypharmacy group of ≥ 15 medications (p < 0.001). A majority (83%) had received drug(s) with the QTc prolongation effect, of whom 67% had actual QTc prolongations in their ECGs. The regression analysis showed that by increasing 6.7% in polypharmacy, one day increase in-hospital survival can be expected. Moreover, an increase of 2.3% in white blood cells or 10.5% in serum potassium level decreased in-hospital survival by 1%.

Conclusion: The findings underscored the importance of careful drug choice, especially in the hectic search for early treatments in pandemics of novel diseases. Close monitoring of patients' drug choice is warranted for reducing pDDIs and their adverse effects in any new disease outbreak.