FDA Adds Boxed Warning to Fezolinetant (Veozah) for Liver Injury Risk

The US Food and Drug Administration (FDA) has added a Boxed Warning to fezolinetant (Veozah) to highlight the known risk of “rare but serious” liver injury associated with use of the medication.1

Announced on December 16, 2024, the warning is based on the FDA’s review of a postmarketing case of serious liver injury reported to the FDA Adverse Event Reporting System (FAERS) database in a patient who experienced symptoms of fatigue; nausea; itching; yellow eyes and skin; light-colored stools; and dark urine within 40 days of starting fezolinetant. Additionally, the patient’s liver blood test values were elevated, including abnormal liver enzymes and bilirubin levels.1

According to a release from the FDA, the patient’s symptoms gradually went away and blood test values slowly returned to normal after discontinuing the treatment, with the agency concluding the patient’s liver injury occurred as a result of treatment with fezolinetant.1

“It’s 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 healthcare 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 (VMS) due to menopause,” Astellas Pharma said in a company 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 VMS due to menopause.”

Fezolinetant was approved for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause on May 12, 2023, making it the first neurokinin 3 receptor antagonist to be approved by the FDA for this indication.2

The decision was supported by positive clinical and safety data from the phase 3 BRIGHT SKY trial program, which included more than 3000 patients across the US, Canada, and Europe. Data from SKYLIGHT 1 and SKYLIGHT 2 emphasized the safety and efficacy of the nonhormonal treatment for VMS associated with menopause, while findings from SKYLIGHT 4 demonstrated the long-term safety of fezolinetant.2

At the time of its approval, the fezolinetant label warned of the risk of elevated hematic transaminase, and 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. Additionally, the agency indicated the treatment could not be used in conjunction with CYP1A2 inhibitors and advised patients with cirrhosis, severe renal damage, or end-stage renal disease to avoid taking the medication.2

On September 12, 2024, the FDA added a warning of liver injury to this caution. In the Drug Safety Communication, the FDA advised halting the medication if signs and symptoms were identified in order to prevent worsening liver injury and potentially restore normal liver function.3

Now, the FDA has added a Boxed Warning, the agency’s most prominent warning, to highlight the known risk of rare but serious liver injury associated with use of fezolinetant based on a postmarketing case of serious drug-induced liver injury caused by use of the medication.1

The FDA recommends patients stop taking fezolinetant immediately and contact their health professional who prescribed the medicine if they experience signs and symptoms suggesting liver problems.1

The FDA recommends healthcare providers perform baseline liver blood tests to assess liver function, including serum ALT; serum AST; serum ALP; total serum bilirubin; and direct serum bilirubin prior to prescribing fezolinetant, and to avoid prescribing the medication if the concentration of ALT, AST, or total bilirubin is ≥ 2 times the upper limit of normal (ULN).1

Additionally, during treatment, providers are advised to perform follow-up liver blood tests every month for the first 3 months, and then again at months 6 and 9 of treatment. If transaminases exceed 5 times the ULN, or if transaminases exceed 3 times the ULN and total bilirubin is > 2 times the ULN, the FDA recommends discontinuing fezolinetant.1

References

1. US Food and Drug Administration. FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause. September 12, 2024. Updated December 16, 2024. Accessed December 17, 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. Petronelli M. FDA Approves Fezolinetant for Moderate to Severe Hot Flashes in Menopause. HCPLive. May 12, 2023. Accessed December 17, 2024. https://www.hcplive.com/view/fda-approves-fezolinetant-for-moderate-to-severe-hot-flashes-in-menopause
3. Iapoce C. FDA Warns of Liver Injury Risk from Fezolinetant for Hot Flashes. HCPLive. September 16, 2024. Accessed December 17, 2024. https://www.hcplive.com/view/fda-warns-of-liver-injury-risk-from-fezolinetant-for-hot-flashes