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Serious liver injury has been observed with fezolinetant (Veoza; Astellas Pharma), a non-hormonal alternative to hormone replacement therapy (HRT), its manufacturer has warned.
In a letter sent to healthcare professionals, Astellas Pharma advised “in agreement with the Medicines and Healthcare products Regulatory Agency (MHRA)” that exposure to [fezolinetant] should be avoided in women at higher risk for liver disease and that early identification of potential liver injury was “essential”.
Fezolinetant was approved for use in the UK for the treatment of hot flushes in menopause in December 2023. It is a neurokinin-3 receptor antagonist that acts on the brain’s thermoregulatory centres to modulate hot flushes and night sweats.
In the letter, Astellas Pharma said that monthly liver function tests (LFTs) must be performed prior to initiation of fezolinetant for the first three months of treatment “and thereafter based on clinical judgement”, owing to the risk of liver injury.
“LFTs must also be performed when symptoms suggestive of liver injury occur,” it added.
“Treatment with fezolinetant must not be initiated if serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) levels are ≥2x ULN or if total bilirubin levels are ≥2x ULN.
“Treatment with fezolinetant must be discontinued if transaminase elevations are ≥3x ULN with total bilirubin >2x ULN OR if patients develop symptoms of liver injury; or transaminase elevations >5x ULN.”
The warnings follow an EU-wide review by the European Medicines Agency of recent safety information on the risk of liver injury in association with the drug.
“Elevations in serum ALT and AST were already observed in clinical trials with fezolinetant and are described in the product information,” the letter said.
However, it added that “serious cases with elevations of ALT and/or AST (>10x ULN) with concurrent elevations in bilirubin and/or alkaline phosphatase (ALP) were reported postmarketing”.
“In some cases, elevated LFTs were associated with signs or symptoms suggestive of liver injury, such as fatigue, pruritus, jaundice, dark urine, decreased appetite or abdominal pain.
“Since Veoza is indicated for a condition in otherwise healthy women, the risk of serious liver injury may significantly affect its benefit–risk balance,” the letter acknowledged.
“Consequently, exposure to Veoza should be avoided in women at higher risk for liver disease and early recognition of potential liver injury is essential.”
It added that elevated LFTs and symptoms suggestive of liver injury were “generally reversible” on discontinuation of therapy.
In a statement to The Pharmaceutical Journal, the British Menopause Society (BMS) said: “In the interests of patient safety, it is not uncommon for drugs new to the market to have additional monitoring requirements recommended, such as the recommendations for monitoring liver function before and during treatment with fezolinetant.
“The BMS shared the MHRA statement about Veoza (fezolinetant), highlighting a risk of drug-induced liver injury and new recommendations on the monitoring of liver function before and during treatment, with its membership on 23 January 2025 and the statement is also available to non-members on the BMS website.
“The BMS awaits update from the MHRA as more data become available.”
