FDA Warns of Liver Injury Risk from Fezolinetant for Hot Flashes

The US Food and Drug Administration (FDA) has released a warning on the rare risk of serious liver injury linked to fezolinetant (Veozah), a treatment for moderate to severe vasomotor symptoms (VMS) due to menopause.¹

The FDA’s Drug Safety Communication from September 12, 2024, advised halting the medication if signs and symptoms were identified, as this may prevent worsening liver injury and potentially restore normal liver function.

“We made this update after reviewing a postmarketing report of a patient with elevated liver blood test values and signs and symptoms of liver injury after taking the medicine for about 40 days,” the agency wrote.¹

Fezolinetant was FDA-approved for the treatment of VMS in May 2023, marking the first neurokinin 3 (NK3) receptor antagonist to receive approval for this indication.² Approval was awarded based on positive clinical and safety data from the Phase 3 BRIGHT SKY trial program, which included more than 3,000 patients across the US, Canada, and Europe.

At the time of approval, the fezolinetant label warned of the risk of elevated hematic transaminase—patients were advised to undergo blood work to test for liver damage before use, followed by routine blood work every 3 months for the 9-month treatment regimen. The agency also indicated the treatment could not be used in conjunction with CYP1A2 inhibitors

In this announcement, the FDA added a warning of liver injury to this caution, after reviewing a post-marketing report of a case with elevated liver blood test values and signals of liver injury after taking fezolinetant for 40 days.¹

Reported to the FDA Adverse Event Reporting System (FAERS), this patient experienced symptoms of fatigue, nausea, itching, yellow eyes and skin, light-colored stool, and dark urine, after starting fezolinetant. The patient’s liver blood tests, including liver enzymes and bilirubin levers, were abnormally elevated.

After the medication was halted, the FDA indicated that the patient’s symptoms and blood test values had gradually returned to normal. Given the variety of factors in a patient’s response to a therapy, the FDA noted they “cannot determine how likely it is that someone will experience these side effects when taking [fezolinetant].”

The agency added new recommendations for healthcare professionals to increase the frequency of liver blood testing for patients taking fezolinetant. These updated recommendations included monthly testing for the subsequent 2 months after starting treatment, with continued evaluation at Months 3, 6, and 9 of treatment, as per the label.

“The updated prescribing information also instructs patients to stop the medicine immediately and contact the health care professional who prescribed the medicine if signs and symptoms of liver injury occur,” the FDA wrote.¹

References

1. _{Center for Drug Evaluation and Research. FDA warns Menopause Drug can cause rare but serious liver injury. U.S. Food and Drug Administration. September 12, 2024. Accessed September 16, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-warning-about-rare-occurrence-serious-liver-injury-use-veozah-fezolinetant-hot-flashes-due?utm_medium=email&utm_source=govdelivery.}
2. _{Petronelli M. FDA approves Fezolinetant for moderate to severe hot flashes in menopause. HCP Live. May 12, 2023. Accessed September 16, 2024. https://www.hcplive.com/view/fda-approves-fezolinetant-for-moderate-to-severe-hot-flashes-in-menopause.}