Remdesivir Discontinuation Decisions Based on Thresholds of Aminotransferase in an Observational Registry.

Autor: Schimmel J; Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, Box 1620, New York, NY, 10029, USA. jonathan_schimmel@alumni.brown.edu., Epperson LC; Parkland Health and Hospital Systems, Dallas, TX, USA.; University of Texas Southwestern Medical Center, Dallas, TX, USA., Aldy K; American College of Medical Toxicology, Phoenix, AZ, USA., Wax P; University of Texas Southwestern Medical Center, Dallas, TX, USA.; American College of Medical Toxicology, Phoenix, AZ, USA., Brent J; School of Medicine, University of Colorado, Aurora, CO, USA., Buchanan J; Department of Emergency Medicine, Denver Health and Hospital Authority, Denver, CO, USA., Levine M; Department of Emergency Medicine, University of California Los Angeles, Los Angeles, CA, USA., Burkhart K; United States Food and Drug Administration, Rockville, MD, USA.
Jazyk: angličtina
Zdroj: Drugs [Drugs] 2024 Feb; Vol. 84 (2), pp. 209-217. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1007/s40265-023-01981-7
Abstrakt: Background: Remdesivir is an antiviral approved by the US Food and Drug Administration (FDA) for treatment of coronavirus disease 2019 (COVID-19), and aminotransferase elevation is commonly reported. Thresholds to be considered for discontinuation due to alanine aminotransferase (ALT) elevation differ between the FDA and European Medicines Agency (EMA). The primary objective was to describe aminotransferase thresholds being used in real-world practice for discontinuation of remdesivir in patients with COVID-19, and compare them with labeled recommendations.
Methods: This study used a descriptive design based on an ongoing national registry of adverse events, the FDA ACMT COVID-19 ToxIC (FACT) pharmacovigilance project, with 17 participating health systems in the USA. Cases were identified retrospectively for an 18-month period (23 November 2020-18 May 2022). Classification of discontinuation as premature and due to aminotransferases was based on chart documentation by the treating team.
Results: Of 1026 cases in the FACT registry, 116 cases were included with supplemental data forms completed for aminotransferase elevation with remdesivir, defined a priori for inclusion as ALT doubling or increasing by ≥ 50 U/L. ALT was elevated prior to remdesivir in 47% and increased above baseline during dosing by a median of 92 U/L [interquartile range (IQR) 51-164, max 8350]. Remdesivir was discontinued early in 37 (31.9%) patients due to elevated aminotransferases. The ALT threshold for premature discontinuation was median 200 U/L (IQR 145-396, range 92-5743). Among patients with premature discontinuation of remdesivir for aminotransferase elevation, only 21.6% met FDA criteria to consider discontinuation, and 40.5% met prior EMA criteria to consider discontinuation.
Conclusion: In this descriptive study of real-world practice in the USA, clinicians are overall making more conservative treatment decisions than are recommended for consideration in approved drug labeling of discontinuation, with wide variation in the aminotransferase thresholds being used.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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