Real-world safety signals of fezolinetant in women with menopausal vasomotor symptoms: a pharmacovigilance analysis of the WHO VigiAccess database.

Abstract

Objectives: To characterize the real-world safety profile of fezolinetant, a neurokinin-3 receptor antagonist approved for the treatment of menopausal vasomotor symptoms, using adverse event reports from the WHO VigiAccess database.

Methods: Adverse event reports were retrieved from VigiAccess. Disproportionality analyses using reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean were applied to identify safety signals. A signal was defined as meeting all four criteria (reporting odds ratio [ROR] lower 95% CI > 1, proportional reporting ratio ≥ 2 with χ² ≥ 4, IC025 > 0, EBGM05 > 2).

Results: A total of 1,091 individual case safety reports comprising 2,143 adverse events were identified, with most reports in women (96.7%) aged 45-64 years (42.16%) and a marked increase in 2024 (n=1,037). Forty-two preferred terms were identified and consistently detected across all methods. The strongest signals included menopausal symptoms (ROR=139.86, 95% CI=75.09-260.53) and facial discomfort (ROR=104.90, 95% CI=33.77-325.87). Liver-related abnormalities showed consistent signals, including increased alanine aminotransferase (ROR=20.60), aspartate aminotransferase (ROR=22.95), and bilirubin (ROR=12.52), suggesting a clustered hepatic signal. Neurological and psychiatric events included insomnia, headache, dizziness, migraine, brain fog, and sleep disorder, whereas gastrointestinal symptoms such as diarrhea and abdominal pain were also observed. Vasomotor symptom-related terms likely reflected the underlying disease rather than treatment effects.

Conclusions: This exploratory analysis found that fezolinetant's real-world safety profile was broadly consistent with phase 3 trials, with efficacy in reducing menopausal vasomotor symptoms. Disproportionality signals mainly involved liver and neurological events. These findings do not reflect absolute risk or incidence and should be considered hypothesis-generating. In view of its established benefit, they support a balanced benefit-risk assessment for clinical use.