Hepatic Adverse Event Signals of Fezolinetant in Real-World Use Based on Postmarketing Surveillance

To evaluate hepatic adverse event reporting associated with fezolinetant after regulatory approval and the U.S. Food and Drug Administration's (FDA) boxed warning using data from the FDA Adverse Event Reporting System.

We conducted a retrospective disproportionality analysis using the FDA's Adverse Event Reporting System database from the second quarter of 2023 through the second quarter of 2025. Reporting odds ratios and 95% CIs were calculated. We performed subgroup analyses, comparative hepatic adverse event assessments against reference drugs, and time-to-onset analyses using the Weibull distribution.

Among 1,282 fezolinetant-associated reports, a hepatic adverse event reporting signal was identified and was predominantly associated with liver enzyme elevations rather than clinically overt hepatic injury. Marked disproportionality was observed in alanine aminotransferase, aspartate aminotransferase, and liver function testing increases. Compared with reference hepatotoxic drugs and hormone therapy agents, fezolinetant was associated with higher reporting signals for laboratory-based abnormalities; however, clinically severe hepatic outcomes were less consistently observed. Median time-to-onset for hepatic events was 77 days (IQR: 30-149), with a Weibull shape parameter consistent with an early failure pattern.

Data identify a signal of hepatic adverse event reporting for fezolinetant, primarily characterized by transaminase elevations rather than clinically overt liver injury. The early failure pattern suggests that hepatic events may tend to occur relatively early after treatment initiation, which highlights the importance of baseline assessment and early-phase monitoring, but continued clinical vigilance remains warranted.