Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database
- PMID: 33340409
- DOI: 10.1002/cpt.2145
Abstract
Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) and authorized conditionally by the European Medicines Agency (EMA) for patients with coronavirus disease 2019 (COVID-19). Its benefit-risk ratio is still being explored because data in the field are rather scant. A decrease of the creatinine clearance associated with remdesivir has been inconstantly reported in clinical trials with unclear relevance. Despite these uncertainties, we searched for a potential signal of acute renal failure (ARF) in pharmacovigilance postmarketing data. An analysis of the international pharmacovigilance postmarketing databases (VigiBase) of the World Health Organization (WHO) was performed, using two disproportionality methods. Reporting odds ratio (ROR) compared the number of ARF cases reported with remdesivir, with those reported with other drugs prescribed in comparable situations of COVID-19 (hydroxychloroquine, tocilizumab, and lopinavir/ritonavir). The combination of the terms “acute renal failure” and “remdesivir” yielded a statistically significant disproportionality signal with 138 observed cases instead of the 9 expected. ROR of ARF with remdesivir was 20-fold (20.3; confidence interval 0.95 [15.7-26.3], P < 0.0001]) that of comparative drugs. Based on ARF cases reported in VigiBase, and despite the caveats inherent to COVID-19 circumstances, we detected a statistically significant pharmacovigilance signal of nephrotoxicity associated with remdesivir, deserving a thorough qualitative assessment of all available data. Meanwhile, as recommended in its Summary of Product Characteristics, assessment of patients with COVID-19 renal function should prevail before and during treatment with remdesivir in COVID-19.
© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Similar articles
-
Remdesivir in the COVID-19 Pandemic: An Analysis of Spontaneous Reports in VigiBase During 2020.Drug Saf. 2021 Sep;44(9):987-998. doi: 10.1007/s40264-021-01091-x. Epub 2021 Aug 10.PMID: 34374967 Free PMC article.
-
Psychiatric Disorders and Hydroxychloroquine for Coronavirus Disease 2019 (COVID-19): A VigiBase Study.Drug Saf. 2020 Dec;43(12):1315-1322. doi: 10.1007/s40264-020-01013-3. Epub 2020 Oct 19.PMID: 33078372 Free PMC article.
-
A Review of the Preclinical and Clinical Efficacy of Remdesivir, Hydroxychloroquine, and Lopinavir-Ritonavir Treatments against COVID-19.SLAS Discov. 2020 Dec;25(10):1108-1122. doi: 10.1177/2472555220958385. Epub 2020 Sep 17.PMID: 32942923 Review.
-
Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications.Expert Rev Clin Pharmacol. 2021 Jan;14(1):95-103. doi: 10.1080/17512433.2021.1856655. Epub 2020 Dec 29.PMID: 33252992 Free PMC article.
-
Hydroxychloroquine and Remdesivir in COVID-19: A critical analysis of recent events.Indian J Med Ethics. 2020 Jul-Sep;V(3):202-207. doi: 10.20529/IJME.2020.068.PMID: 33295289 Review.
Cited by 5 articles
-
Remdesivir in the COVID-19 Pandemic: An Analysis of Spontaneous Reports in VigiBase During 2020.Drug Saf. 2021 Sep;44(9):987-998. doi: 10.1007/s40264-021-01091-x. Epub 2021 Aug 10.PMID: 34374967 Free PMC article.
-
Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.Kidney Int Rep. 2021 Sep;6(9):2305-2315. doi: 10.1016/j.ekir.2021.06.023. Epub 2021 Jul 6.PMID: 34250317 Free PMC article.
-
Pathophysiology of COVID-19-associated acute kidney injury.Nat Rev Nephrol. 2021 Jul 5:1-14. doi: 10.1038/s41581-021-00452-0. Online ahead of print.PMID: 34226718 Free PMC article. Review.
-
Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System.Pharmaceuticals (Basel). 2021 Jun 25;14(7):611. doi: 10.3390/ph14070611.PMID: 34202350 Free PMC article.
-
Kidney disorders as serious adverse drug reactions of remdesivir in coronavirus disease 2019: a retrospective case-noncase study.Kidney Int. 2021 May;99(5):1235-1236. doi: 10.1016/j.kint.2021.02.015. Epub 2021 Feb 26.PMID: 33647327 Free PMC article. No abstract available.
References
-
- Jorgensen, S.C.J., Kebriaei, R. & Dresser, L.D. Remdesivir: review of pharmacology, pre-clinical data, and emerging clinical experience for COVID-19. Pharmacother. J. Hum. Pharmacol. Drug Ther. 40, 659-671 (2020).
-
- Tchesnokov, E.P., Feng, J.Y., Porter, D.P. & Götte, M. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses 11, 326 (2019).
-
- Agostini, M.L. et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 9, e00221-18 (2018).
-
- FDA. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. FDA <https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19…> (2020).
-
- EMA. First COVID-19 treatment recommended for EU authorisation. European Medicines Agency <https://www.ema.europa.eu/en/news/first-covid-19-treatment-recommended-e…> (2020).