Evaluation of potential drug-drug interactions and polypharmacy in hospitalized COVID-19 patients

Background: Drugs that are used in COVID-19 infection, may interact with each other, as well as with the drugs for comorbidities, used concomitantly with COVID-19 treatment. Objectives: It is quite important to calculate and present the patients' exposure to clinically important potential drug-drug interactions (pDDIs). We aimed to investigate the pDDIs and the burden of polypharmacy in COVID-19. Methods: The medical records of 126 consecutive inpatients with COVID-19 treatment were retrospectively analyzed. The Lexi-interact database was used to investigate pDDIs. Results: According to the Lexi-interact database, 605 pDDIs were detected. Of these pDDIs, 23 (3.8%) were A risk category interaction, 186 (30.7%) were B risk category interaction, 339 (56%) were C risk category interaction, 54 (8.9%) were D risk category interaction, and 3 (0.5%) were X risk category interaction. Sixty-five-point five percent of pDDIs (n=396) were clinically important pDDIs (C, D, and X categories), and 69 patients (54.8%) had at least one clinically important pDDIs. The most interacting drug was hydroxychloroquine (n=171, 28.3%). Hydroxychloroquine was also the most interacting drug in the C risk category (n=101, 29.8%) and had 19 pDDIs with metformin, 16 pDDIs with beta-blockers, 13 pDDIs with acetylsalicylic acid, and 10 pDDIs with insulin in the C risk category. Enoxaparin was the most interacting drug (n=25, 46.3%) in the D risk category and most of them were with acetylsalicylic acid (n=12). The most common possible clinical manifestations of pDDIs were QT prolongation, hypoglycemia, and hemorrhage. One hundred and eighteen patients (93.6%) used five or more drugs daily. There was a significant positive correlation between the number of drugs prescribed to patients and the number of clinically important pDDIs (r=0.80, p<0.001). Conclusions: Clinically important pDDIs are common among COVID-19 patients and the majority of pDDIs require monitoring of therapy. COVID-19 patients should be closely observed for QT prolongation, hypoglycemia, and hemorrhage due to pDDIs during treatment.