FDA Adds Boxed Warning to Hot Flash Drug

The FDA slapped a boxed warning on fezolinetant (Veozah), a hormone-free pill for moderate to severe hot flashes caused by menopause, highlighting the known risk of rare but serious liver injury associated with use of the drug, the agency announced.

In September, the FDA issued an initial drug safety communication warning about this rare occurrence, prompted by a postmarketing report submitted to its Adverse Event Reporting System database.

In that case, the patient had significantly elevated liver blood test values within 40 days of starting fezolinetant, including alanine transaminase more than 10 times the normal level, alkaline phosphatase more than four times the normal level, and total bilirubin more than three times the normal level. The patient felt generally unwell and had symptoms associated with liver injury, including fatigue, nausea, decreased appetite, itching of hands and feet that later spread to the entire body, jaundice, pale feces, and dark urine. The patient’s liver blood test values returned to normal and other symptoms gradually resolved after discontinuing the drug.

“We concluded this patient had liver injury as a result of Veozah treatment,” the FDA noted.

The updated prescribing information states that hepatotoxicity has occurred in the postmarketing setting and encourages hepatic laboratory tests — including serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and total and direct bilirubin levels — prior to starting fezolinetant in order to have a baseline for hepatic function and injury. Performing follow-up hepatic laboratory testing monthly for the first 3 months, at 6 months, and at 9 months of treatment is also recommended.

The boxed warning also advises that patients not start fezolinetant if an initial evaluation finds that aminotransferase levels or total bilirubin levels are at or exceed two times the upper limit of normal (ULN). The drug should be discontinued if transaminase levels are greater than five times the ULN, or if the transaminase levels are more than three times the ULN and the total bilirubin level is more than two times the ULN.

Additionally, if transaminase levels are greater than three times the ULN, follow-up hepatic laboratory testing should be performed more frequently until the issue is resolved.

If anyone taking the drug experiences signs or symptoms of liver injury, they should stop taking the drug to prevent worsening liver injury and to potentially return liver function to normal, the agency said. Symptoms could include fatigue, vomiting, unusual itching, light-colored feces, dark urine, jaundice, abdominal swelling, or right upper quadrant pain. Patients experiencing symptoms are also encouraged to seek medical attention, including hepatic laboratory testing.

The oral neurokinin 3 receptor antagonist was approved in May 2023 and is the first non-hormonal treatment for vasomotor symptoms.

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