(P-375) Remdesivir Safety Monitoring During the COVID-19 Pandemic: A Global Review of Adverse Drug Reaction (ADR) Reporting in Vigibase

Background: Remdesivir (RDS) is conditionally approved for the treatment of COVID-19 in several countries. With its poorly characterised safety profile, global monitoring of ADR reporting is essential.

Objectives: Reviewing global ADR reporting for remdesivir by investigating severity of illness, co-reported COVID-19 medications, characteristics of early therapy cessation and ADRs in individual case safety reports (ICSR).

Methods: All COVID-19-specific ICSRs were retrieved from the WHO global ICRS database, VigiBase, by scanning incoming ICSR’s indication, free text and laboratory test result fields through an in-house developed algorithm until Dec 31, 2020. Drugs in extracted ICSRs were classified by two independent coders as either COVID-19 specific (identified from scientific literature) or non-COVID-19 specific. Analysis of the RDS ICSR’s demographics, co-reported drugs, therapy duration, time to reaction’s onset (TTO), adverse drug reactions coded as MedDRA preferred terms (PTs), and manual review of narratives was performed. Disproportionality analysis (DA) was performed for signal detection purposes using COVID-19 specific drugs as background to reduce confounding by the disease.

Results: Of 5297 ICSRs where RDS was mentioned, 60.6% concerned males of median age 63 and originated from the Americas (72.8%). 97.2% had RDS as suspected drug. 21% of the RDS ICSRs were co-reported with PT/concomitant drugs indicating severe COVID-19. Co-reported drugs (median 3, IQR 1-8) were initiated up to 15 days prior to RDS initiation , increasing in numbers until reaching a maximum on the day of RDS initiation and day 1-2 afterwards. Most frequent co-reported COVID-19 drugs were heparins, corticosteroids and azithromycin. 41% of the RDZ ICSRs with complete date information had a therapy duration shorter than the minimum 5 days recommended. In a sample of 47 early withdrawal ICSRs, 36 indicated safety concerns, with variable clinical certainty of causal association with RDV. Among most disproportionate ADRs reported were liver dysfunction, kidney injury, bradycardia, the latter two not yet included in labelling. Causality assessment was challenging due to polypharmacy and unknowns related to COVID-19 and RDV.

Conclusions: RMD’s ICSRs show a complex pattern of care and polypharmacy making causality assessment complex. In-depth analysis of case narratives, including clinicians’ safety concerns in the extensive withdrawal patterns, may aid in further evaluating the ADRs related to eg hepatic, renal and cardiac function.