FDA Updates Veozah Label With Boxed Warning for Rare But Serious Liver Injury

The FDA has added a Boxed Warning for rare but serious liver injury to the labeling of fezolinetant (Veozah), an oral neurokinin 3 receptor antagonist approved to treat moderate to severe vasomotor symptoms—such as hot flashes and night sweats—caused by menopause.¹

The patient’s symptoms gradually resolved after discontinuing fezolinetant therapy. | image credit: loran4a - stock.adobe.com

This warning joins a previous warning about elevated liver blood test values and required liver blood testing. According to the agency, the decision to add a Boxed Warning was made after reviewing a postmarketing report of a patient who experienced elevated liver blood test values, as well as signs and symptoms of liver injury, aftering taking fezolinetant for approximately 40 days. The FDA also added recommendations for increased frequency of liver blood testing: In addition to regular testing at months 3, 6, and 9, patients should also be tested monthly for 2 months after starting fezolinetant therapy.

The patient case was reported to the FDA Adverse Event Reporting System (FAERS) database. According to the report, the patient experienced symptoms of fatigue, nausea, itching, yellow eyes and skin, light colored stool, and dark colored urine within the first 40 days of starting fezolinetant therapy. Liver blood test values were elevated, including abnormal liver enzymes and bilirubin levels. Symptoms and lab values gradually returned to normal after discontinuing therapy.

READ MORE: Women With Delayed Menopause May Face Increased Risk of Asthma

“It is important to note that the overall benefit-risk of Veozah has not changed and remains positive, but we want to further ensure that patients and health care providers are aware of the potential side effects of Veozah, and the hepatic laboratory testing, as it relates to its benefit to help reduce moderate to severe vasomotor symptoms due to menopause,” said manufacturer Astellas Pharma in an emailed statement. “We remain confident in the overall safety profile of Veozah and its ability to provide appropriate patients with a nonhormonal treatment option for moderate to severe [vasomotor symptoms] due to menopause.”

Fezolinetant was approved by the FDA on May 12, 2023.² Based on data from the Bright Sky Phase 3 program, which included the SKYLIGHT 1 (NCT04003155) and SKYLIGHT 2 (NCT04003142), each of which enrolled over 1000 participants (mean age, 54 years) experiencing moderate to severe vasomotor symptoms. These trials each included a 12-week double-blinded, placebo-controlled phase followed by a 40-week treatment extension period.³

The balance between estrogen and neurokinin B work to regulate the body’s temperature control center. However, during menopause, estrogen declines and the balance is disrupted. This imbalance is what leads to vasomotor symptoms, which fezolinetant helps re-balance by blocking neurokinin B in the brain’s temperature control center.

READ MORE: Women’s Health Resource Center

References

1. FDA adds warning about rare occurrence of serious liver injury with Veozah (fezolinetant) for hot flashes due to menopause. FDA. Updated December 16, 2024. Accessed December 18, 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

2. FDA approves novel drug to treat moderate to severe hot flashes caused by menopause. FDA. News release. May 12, 2023. Accessed December 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause

3. Biscaldi L. FDA approves fezolinetant, a novel therapy for vasomotor symptoms in menopause. May 12, 2023. Accessed December 18, 2024. https://www.drugtopics.com/view/fda-approves-fezolinetant-a-novel-therapy-for-vasomotor-symptoms-in-menopause