Disproportionality analysis and “perpetrator” or “accomplice” review of Baloxavir Marboxil in public FAERS database

Abstract Background Baloxavir marboxil (Xofluza™) was approved global in 2018, which is a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Despite indicating that Baloxavir marboxil is effective and well-tolerated through a series of clinical trials, studies on its safety in real-world settings are scarce. Methods We conducted an evaluation of adverse events associated with Baloxavir marboxil by means of data mining within the FDA Adverse Event Reporting System (FAERS) database spanning from the fourth quarter of 2018 to the second quarter of 2024. Initially, we used four algorithms designed for disproportionality analysis (ROR, PRR, BCPNN, and MGPS) to identify signals of disproportionate reporting. Subsequently, we conducted a detailed differential analysis on the identified signals, examining variables such as sex, age, and concomitant medication usage. Furthermore, we undertook a case-by-case review of indications and co-administered drugs to elucidate the clinical contexts of the affected patient populations. Results 1765 reports and 3624 adverse events with Baloxavir marboxil as the primary suspected drug were filtered out. 35 signals of disproportionate reporting involving 15 system organ class were identified, including two unexpected adverse reaction signals: rhabdomyolysis and international normalised ratio increased. Males, especially those over 65 years old, contributed most to the reports of rhabdomyolysis. In a case-by-case analysis of the DRUG dataset regarding co-administered medications, (i) all patients taking warfarin concomitantly, with a median age of 68, experienced elevated INR levels or other severe hemorrhagic events, and the Ω shrinkage measure for the Baloxavir marboxil - warfarin interaction yielded a result of Ω₀₂₅ = 1.42; (ii) the usage frequency of hypotensive agents across the study population was considerable, ranking just below that of influenza-related pharmaceuticals, specifically NSAIDs and antibiotics; (iii) among the deceased patients, whose median age was 73, their medication profile indicated a high utilization of hypotensive agents, in addition to NSAIDs and antitussive & expectorant & antiasthmatic agents. Conclusion This research has enhanced the comprehension of the safety spectrum of Baloxavir marboxil, offering novel insights for its clinical application. Definitive risk management strategies still require large-scale clinical and experimental research.