Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database

Abstract

The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Factors Contributing to Chronic Kidney Disease following COVID-19 Diagnosis in Pre-Vaccinated Hospitalized Patients

“…Although remdesivir is deemed to be a relatively nephrotoxic agent and usually is administered to patients with more severe COVID-19 infection, affected patients are more vulnerable to the development of AKI. Administration of remdesivir is not recommended in patients with an eGFR below 30 mL/min [ 58 , 59 , 60 ]. In some studies [ 59 , 60 ], using remdesivir for COVID-19 treatment was reported to increase the risk of developing AKI as compared to using other drugs, such as tocilizumab, hydroxychloroquine, and lopinavir/ritonavir.…”

“…Administration of remdesivir is not recommended in patients with an eGFR below 30 mL/min [ 58 , 59 , 60 ]. In some studies [ 59 , 60 ], using remdesivir for COVID-19 treatment was reported to increase the risk of developing AKI as compared to using other drugs, such as tocilizumab, hydroxychloroquine, and lopinavir/ritonavir. In fact, administration of remdesivir for more than five days was reported to worsen AKI [ 58 , 61 ], except for a single study by Izcovich et al where remdesivir was reported to pose no significant risk for AKI when used as a COVID-19 treatment [ 62 ].…”

Remdesivir: Effectiveness and safety in hospitalized patients with COVID-19 (ReEs-COVID19) - Analysis of data from daily practice

“…Poor prognosis for COVID-19 patients with AKI complication has already been described (35,36). Even if AKI is uncommon in COVID-19 patients receiving remdesivir, there should be appropriate renal function monitoring and pharmacovigilance alert (37)(38)(39)(40). Covid-19 can result in renal impairment; however, prompt treatment may contribute, in preventing AKI occurrence (41,42).…”

Pharmacologic Treatment and Management of Coronavirus Disease 2019

“…Remdesivir is solubilized in a vehicle that is renally eliminated and remdesivir is not recommended for patients with an estimated glomerular filtration rate of less than 30 mL/min. Case series are available to support the use in creatinine clearance < 30 mL/min 38 , 39 , 40 , however pharmacovigilance reports provide evidence for adverse renal outcomes 41 , 42 , so providers must assess the risk vs. benefit of remdesivir use and consultation with pharmacy colleagues is recommended. Transaminase elevations may occur with remdesivir and clinicians should consider discontinuing use if ALT levels increase to greater than 10x the upper limit of normal.…”