FDA Updates Felinzanetant Label Warnings After Report of Severe Liver Injury

In response to a postmarketing report of signs and symptoms of a rare, serious liver injury in a patient treated with fezolinetant (Veozah; Astellas), the FDA has added a warning to the medication’s professional prescribing information about elevated liver function test (LFT) values that includes requirements for increased frequency of LFT testing after initiating fezolinetant treatment.¹

In a Drug Safety Communication issued this week the agency¹ described details of a report submitted to its Adverse Event Reporting System of a woman who experienced elevated LFT values and related signs and symptoms within 40 days of beginning treatment.

The patient’s laboratory values indicated an alanine transaminase (ALT) level more than 10 times normal, an alkaline phosphatase level more than 4 times normal, and her total bilirubin measured 3 times the average level. The primary symptoms reported were fatigue, nausea, itching, yellowed eyes and skin, light-colored stool, and dark urine. The FDA confirmed that symptoms gradually resolved and LFT values slowly normalized after fezolinetant treatment was discontinued.¹

Fezolinetant was approved by the FDA as the first non-hormonal treatment for vasomotor symptoms (VMS) associated with menopause in May 2023. The mechanism of the once-daily neurokinin-3 receptor antagonist restores balance between estrogen and neurokinin B by blocking activity that impacts the brain’s thermoregulatory center.²

The original label approved by the FDA included a warning regarding the risk of elevated hepatic transaminase that indicated concentrations 3 times the upper limit of normal (ULN) had been observed during clinical trials of fezolinetant. It called for clinicians to evaluate hepatic function and injury before initiating treatment. Therapy was contraindicated in any person with serum transaminase levels equal to or greater than 2 times ULN.²

At that time, the FDA-approved prescribing information recommended follow-up testing of ALT at 3, 6, and 9 months after initiating treatment.²According to the FDA safety communication, the agency “added new recommendations…about increasing the frequency of liver blood testing, adding monthly testing for the next 2 months after starting [fezolinetant], and then at months 3, 6, and 9 of treatment as already recommended. 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.”¹

Hepatic cirrhosis was included as contraindication to fezolinetant use prior to the current report as were severe renal impairment or end-stage renal disease, and use of CYP1A2 inhibitors.²

Astellas Pharma has responded to the FDA's warning, stating, "We are committed to ensuring the hepatic laboratory testing protocol in the VEOZAH US prescribing information identifies patients at risk for or experiencing symptoms of potential drug-induced liver injury as early as possible and therefore have added 2 additional timepoints for hepatic tests to the label, testing for an additional liver value, as well as guidance on when to seek medical attention and when to discontinue VEOZAH."

References

1. US Food & Drug Administration. FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause. FDA Drug Safety Communication. Published September 12, 2024. Accessed September 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. Veozah [package insert]. Northbrook, IL: Astellas Pharma US, Inc; 2024.
3. Jennings S. FDA approves novel drug for treatment of hot flashes caused by menopause. Patient Care. May 15, 2023. https://www.patientcareonline.com/view/fda-approves-novel-drug-for-the-treatment-of-hot-flashes-caused-by-menopause