J Korean Med Sci.  2023 Nov;38(44):e346. 10.3346/jkms.2023.38.e346.

Adverse Drug Events Associated With Remdesivir in Real-World Hospitalized Patients With COVID-19, Including Vulnerable Populations: A Retrospective Multicenter Study

• Kang H
• Kang CK
• Im JH
• Cho Y
• Kang DY
• Lee JY

• KMID: 2547969
• DOI: http://doi.org/10.3346/jkms.2023.38.e346

Abstract

Background
Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women.
Methods
This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women.
Results
Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085).
Conclusion
A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

Keyword

Coronavirus Disease 2019; Remdesivir; Hepatic Impairment; Renal Impairment; Pregnancy

Figure

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  Fig. 1 Incidence proportion of ADEs and severe ADEs in subpopulations treated with remdesivir. Data are represented as below: renal impairment = patient with pre-treatment estimated glomerular filtration rate < 30 mL/min; hepatic impairment = patient with alanine aminotransferase value > 5 × the upper limit of normal at pre-treatment; pregnancy = pregnant women; control = controls matched to each subpopulation.ADE = adverse drug event.

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