FDA Warning on Hot Flash Drug

The FDA warned that fezolinetant (Veozah), a hormone-free pill for moderate to severe hot flashes caused by menopause, could cause rare but serious liver injury.

If women experience any signs or symptoms suggesting liver injury, they should stop fezolinetant, the agency said. Symptoms include new-onset fatigue, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or right upper quadrant pain.

Treatment discontinuation may prevent worsening liver injury and may potentially return liver function to normal, the FDA explained.

Prompting the warning was a postmarketing report submitted to the FDA’s Adverse Event Reporting System (FAERS) database in which a patient had elevated liver blood test values and signs and symptoms of liver injury within 40 days of starting the drug.

The patient experienced symptoms of fatigue, nausea, itching, yellow eyes and skin, light-colored stools, and dark urine. Labs indicated alanine transaminase (ALT) was more than 10 times the normal level, alkaline phosphatase was more than four times the normal level, and total bilirubin was more than three times the normal level.

Symptoms gradually resolved and blood test values slowly returned to normal after the patient stopped fezolinetant.

The agency detailed new requirements for liver blood testing on the updated label. Healthcare providers should perform baseline liver blood tests to assess liver function prior to starting treatment, including ALT, aspartate aminotransferase (AST), alkaline phosphatase, and total and direct bilirubin. Providers should not start treatment if the concentrations of ALT, AST, or total bilirubin are equal to or exceed two times the upper limit of normal (ULN).

“We also added new recommendations for patients and healthcare professionals about increasing the frequency of liver blood testing, adding monthly testing for the next 2 months after starting Veozah, and then at months 3, 6, and 9 of treatment as already recommended,” the FDA noted in a safety communication.

Alternative causes of liver injury should be excluded if liver blood tests are elevated.

Fezolinetant should be stopped if transaminase levels exceed five times the ULN or if transaminase levels exceed three times the ULN and total bilirubin is more than two times the ULN. More frequent follow-up liver blood testing should be performed if the transaminases exceed three times the ULN, but the total bilirubin is not more than two times the ULN.

Known cirrhosis was previously listed as a contraindication to fezolinetant use prior to this report. Other contraindications include severe renal impairment or end-stage renal disease, and use of CYP1A2 inhibitors.

The first-in-class pill — an oral neurokinin 3 receptor antagonist — was approved in May 2023. It marked the first non-hormonal treatment for vasomotor symptoms.

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