tetano
Editor, Senior Moderator
Clin Pharmacol Ther
. 2020 Dec 19.
doi: 10.1002/cpt.2145. Online ahead of print.
Remdesivir and acute renal failure: a potential safety signal from disproportionality analysis of the WHO safety database
Alexandre G?rard[SUP] 1 2 [/SUP], Audrey Laurain[SUP] 1 [/SUP], Audrey Fresse[SUP] 2 [/SUP], Nad?ge Parassol[SUP] 2 [/SUP], Marine Muzzone[SUP] 2 [/SUP], Fanny Rocher[SUP] 2 [/SUP], Vincent L M Esnault[SUP] 1 [/SUP], Milou-Daniel Drici[SUP] 2 [/SUP]
Affiliations
Abstract
Remdesivir is approved for emergency use by the 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 since 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, 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; CI 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 COVID-19 patients' renal function should prevail before and during treatment with remdesivir in COVID-19.
Keywords: COVID-19; acute renal failure; clinical epidemiology; drug nephrotoxicity; remdesivir.
. 2020 Dec 19.
doi: 10.1002/cpt.2145. Online ahead of print.
Remdesivir and acute renal failure: a potential safety signal from disproportionality analysis of the WHO safety database
Alexandre G?rard[SUP] 1 2 [/SUP], Audrey Laurain[SUP] 1 [/SUP], Audrey Fresse[SUP] 2 [/SUP], Nad?ge Parassol[SUP] 2 [/SUP], Marine Muzzone[SUP] 2 [/SUP], Fanny Rocher[SUP] 2 [/SUP], Vincent L M Esnault[SUP] 1 [/SUP], Milou-Daniel Drici[SUP] 2 [/SUP]
Affiliations
- PMID: 33340409
- DOI: 10.1002/cpt.2145
Abstract
Remdesivir is approved for emergency use by the 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 since 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, 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; CI 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 COVID-19 patients' renal function should prevail before and during treatment with remdesivir in COVID-19.
Keywords: COVID-19; acute renal failure; clinical epidemiology; drug nephrotoxicity; remdesivir.