Dear Editor
A few days after Dr Geraci and Professor Kuokkanen’s editorial was published, the European Medicines Agency (EMA) announced new recommendations to minimise risk of liver injury from fezolinetant (Veoza). Liver function tests (LFTs), they state, must be performed before treatment is started and, during the first three months of treatment, monthly LFTs must be carried out (1).
This is because “severe elevations of the liver enzymes alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (>10x upper limit of normal) with concurrent elevations in bilirubin and/or alkaline phosphatase (ALP) have been reported post marketing in women taking Veoza. In some cases, elevated liver function tests (LFTs) were associated with signs or symptoms suggestive of liver injury such as fatigue, pruritus, jaundice, dark urine, decreased appetite, or abdominal pain” (1).
The FDA had already issued a warning in September 2024 after a report of a patient with elevated liver function test values and signs and symptoms of liver injury after taking the medicine for about 40 days (2).
This should come as no surprise as development of another neurokinin 3 receptor antagonist, MLE4901, Pavinetant was discontinued in 2017 because of liver toxicity (3). Clearly fenoxidant does not only act on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron (4).
According to the linked research (5) “An independent panel of three liver experts (liver safety monitoring panel) evaluated participants for potential drug induced liver injury who met the criterion of alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of normal (sic)…” and that “no participants had drug induced liver injury according to Hy’s law”. (Hy’s law applies to patients at high risk of a fatal drug-induced liver injury) (6).
Geraci and Kuokkanen’s editorial repeats that in the trial there was “no drug induced liver injury”.
I find it concerning that the consensus seems to be that, providing a drug only mildly damages the liver, this is acceptable.
1, https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-r…
2, https://www.fda.gov/safety/medical-product-safety-information/fda-adds-w…
3, Prague, Julia K et al., Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. DOI: 10.1016/S0140-6736(17)30823-1
4, https://mhraproducts4853.blob.core.windows.net/docs/5a51dd236244e9ab5bb6…
5, https://www.bmj.com/content/387/bmj-2024-079525
6, https://www.fda.gov/media/116737/download
Fezolinetant and the Liver