Avacopan-Associated Hepatobiliary Adverse Events and Vanishing Bile Duct Syndrome: A PMDA/JADER and FAERS Reporting-Profile Comparison.

Abstract

Aim: Avacopan is an oral C5a receptor antagonist approved for anti-neutrophil cytoplasmic antibody-associated vasculitis. Recent post-marketing safety information has raised concern regarding serious hepatobiliary injury, including vanishing bile duct syndrome (VBDS). We compared Japanese and FAERS post-marketing reporting profiles for avacopan-associated adverse events.

Methods: FAERS public dashboard data and PMDA CSV data downloaded in May 2026 were searched using Japanese and English avacopan/Tavneos terms and analyzed at the case report and adverse-event/preferred-term row levels. FAERS Public Dashboard aggregate data were searched using the avacopan generic-name listing as the primary definition and the Tavneos product-name listing as a sensitivity definition.

Results: PMDA/JADER contained 397 avacopan-related reports and 744 adverse-event/preferred-term rows. FAERS contained 5770 reports in the avacopan generic-name listing and 5216 reports in the Tavneos product-name listing. Hepatobiliary preferred terms were prominent in PMDA/JADER, including hepatic function abnormal (n = 86), liver disorder (n = 44), drug-induced liver injury (n = 40), and VBDS (n = 29). Among PMDA/JADER VBDS reports with available dates, the median time to onset was 44.0 days (interquartile range, 39.5-52.0).

Conclusions: Post-marketing reports of avacopan-associated hepatobiliary injury, including VBDS, warrant clinical attention, particularly during the early treatment period. PMDA/JADER and FAERS findings should be interpreted as differences in reporting profiles rather than direct comparisons of incidence or risk.