Is remdesivir safe in patients with renal impairment? Experience at a large tertiary urban medical center

Abstract

Purpose Remdesivir is FDA-approved for treatment of patients hospitalized with COVID-19 pneumonia, but not recommended in patients with severe renal failure. This study aims to evaluate the safety of remdesivir in this patient population. Methods This was a single-center, retrospective cohort study including patients ≥ 18 years old, admitted between May 1, 2020 and April 30, 2021 who received remdesivir. Patients were divided into two groups: estimated creatinine clearance (eCrCl) < 30 mL/min and eCrCl ≥ 30 ml/min. Primary outcomes were development of acute kidney injury (AKI) after remdesivir initiation and hepatotoxicity (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 5 × upper limit of normal) both at end of treatment (EOT) or 5 days after EOT. Secondary outcomes were length of stay (days) and mortality. Results 513 patients were assessed with 416 patients included in the study (eCrCl < 30 mL/min, n = 55; eCrCl ≥ 30 mL/min n = 361). Incidence of AKI (eCrCl < 30 mL/min 11% vs eCrCl ≥ 30 mL/min 7%, OR 1.57, 95% CI 0.57, 4.3) and hepatotoxicity (ALT: 2% vs 4%, OR 0.47, 95% CI 0.05, 3.7 and AST: 2% vs 2%, OR 1.26, 95% CI 0.14, 11.04) were similar between the two groups. Length of stay was longer in the eCrCl < 30 mL/min group (mean 18.6 vs 11.9, difference 6.7, 95% CI 3.8, 9.6), and no difference in mortality was observed (21.8% vs 18.8%, OR 1.2, 95% CI 0.6, 2.4). Conclusion Remdesivir was not associated with development of AKI or hepatotoxicity in patients with eCrCl < 30 mL/min compared to patients with eCrCl ≥ 30 mL/min, and warrants further investigation.

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

“…In a study of 416 patients in New York, 55 patients had renal impairment with CrCl (eCrCl) < 30 mL/min, and there was no significant difference in the incidence of AKI and hepatotoxicity compared to those without. 19 In this study, the definitions of renal injury and hepatic injury were different from our study, so there may be differences in the results. In addition, a study investigating 46 patients with renal impairment using remdesivir in India concluded that remdesivir was well tolerated by patients with AKI or chronic kidney disease.…”

“… 18 In addition, a retrospective study conducted at a hospital in New York found that remdesivir was not associated with acute kidney injury (AKI) or hepatotoxicity in patients with estimated creatinine clearance (eCrCl) < 30 mL/min compared to those with eCrCl ≥ 30 mL/min. 19 However, safety data on remdesivir in real-world clinical situations, particularly in vulnerable populations, are insufficient. Few studies have investigated the safety of remdesivir in renal impairment patients.…”

Remdesivir use for COVID-19 patients: Rates of serum creatinine levels to baseline or to upper limits to monitor postadministration renal function

“…Our series showed that peak SCr ratios were on Day 3, corresponding to their report. Sunny and others [7], however, reported that remdesivir was not associated with the development of AKI or hepatotoxicity in patients with an estimated creatinine clearance < 30 mL/min.…”

“…We assessed the following background status parameters: (1) eGFR < 30 ml/min/1.73 m 2 , (2) SCr ratios to baselines > 1.5, (3) SCr ratios to upper limits > 1.5 (Grade 2), (4) ALT ratios to upper limits > 5 (Grade 3), (5) remdesivir administration > = 4 days, (6) sex, (7) age, (8) height, (9) weight, (10) use of dexamethasone, and (11) number of SARS-CoV-2 vaccinations. We used Excel 2019 software (Microsoft Inc., Redmond, WA, USA) to generate line graphs depicting the time course of laboratory data.…”

Synthesis and evaluation of NHC derivatives and 4′-fluorouridine prodrugs

“…As a well-known class of antiviral agents, nucleoside analogs that function by targeting the conserved active site of viral polymerase have been of research interest in the discovery of antiviral drugs. In recent years, two nucleoside drugs, remdesivir 2 and molnupiravir, 3 used for treating COVID-19 have been marketed, and their application may be further expanded due to their broad-spectrum antiviral properties. 4,5 β-D-N 4 -Hydroxycytidine (NHC, EIDD-1931), a cytidine analog, is the parent nucleoside of molnupiravir (EIDD-2801) (Fig.…”