Adverse drug event risk assessment by the virtual addition of COVID-19 repurposed drugs to Medicare and commercially insured patients' drug regimens: A drug safety simulation study.

Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE

Original Publication: Malden, MA : WileyBlackwell Pub., 2008-

Drug Repositioning* ; COVID-19 Drug Treatment*; Antiviral Agents/*adverse effects ; Long QT Syndrome/*epidemiology; Administrative Claims, Healthcare/statistics & numerical data ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacokinetics ; COVID-19/complications ; COVID-19/virology ; Child ; Child, Preschool ; Computer Simulation ; Cytochrome P-450 Enzyme System/metabolism ; Drug Interactions ; Female ; Humans ; Infant ; Infant, Newborn ; Long QT Syndrome/chemically induced ; Male ; Medicare/statistics & numerical data ; Middle Aged ; Pharmacovigilance ; Retrospective Studies ; Risk Assessment/methods ; Risk Assessment/statistics & numerical data ; United States/epidemiology ; Young Adult

Drug safety is generally established from clinical trials, by pharmacovigilance programs and during observational phase IV safety studies according to drug intended or approved indications. The objective of this study was to estimate the risk of potential adverse drug events (ADEs) associated with drugs repurposed for coronavirus disease 2019 (COVID-19) treatment in a large-scale population. Drug claims were used to calculate a baseline medication risk score (MRS) indicative of ADE risk level. Fictitious claims of repurposed drugs were added, one at a time, to patients' drug regimens to calculate a new MRS and compute a level of risk. Drug claims data from enrollees with Regence health insurance were used and sub-payer analyses were performed with Medicare and commercial insured groups. Simulated interventions were conducted with hydroxychloroquine and chloroquine, alone or combined with azithromycin, and lopinavir/ritonavir, along with terfenadine and fexofenadine as positive and negative controls for drug-induced Long QT Syndrome (LQTS). There were 527,471 subjects (56.6% women; mean [SD] age, 47 years [21]) were studied. The simulated addition of each repurposed drug caused an increased risk of ADEs (median MRS increased by two-to-seven points, p < 0.001). The increase in ADE risk was mainly driven by an increase in CYP450 drug interaction risk score and by drug-induced LQTS risk score. The Medicare group presented a greater risk overall compared to the commercial group. All repurposed drugs were associated with an increased risk of ADEs. Our simulation strategy could be used as a blueprint to preemptively assess safety associated with future repurposed or new drugs.
(© 2021 TabulaRasa Health Care and Cambia Health Solutions. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

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Tabula Rasa HealthCare

0 (Antiviral Agents)
9035-51-2 (Cytochrome P-450 Enzyme System)

Date Created: 20210331 Date Completed: 20211018 Latest Revision: 20231107

20231107

PMC8251090

10.1111/cts.13025

33786990