The US Food and Drug Administration (FDA) has issued a warning regarding the risk of fezolinetant (Veozah) to cause rare, serious liver injuries to patients.1
Astellas statement on VEOZAH prescribing information
"Patient safety is Astellas’ top priority, and we work regularly with the U.S. Food and Drug Administration (FDA) and other regulatory authorities to monitor the safety profile of our medications, which may include updating product labels. The VEOZAH U.S. prescribing information notifies healthcare providers (HCPs) and patients to complete regular hepatic laboratory tests to ensure patients are appropriately managed following treatment initiation.
The FDA has identified a probable case of serious drug induced liver injury that occurred in a woman in the U.S. receiving VEOZAH with symptoms of fatigue, nausea, pruritus, jaundice, pale feces and dark urine. The individual’s abnormalities gradually resolved after discontinuation of the drug.
We are committed to ensuring the hepatic laboratory testing protocol in the VEOZAH U.S. prescribing information identifies patients at risk for or experiencing symptoms of potential drug induced liver injury as early as possible and therefore have added two 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.
Specifically, the updated testing protocol is a baseline test, monthly tests for the first 3 months, at 6 months and 9 months after initiation of therapy and testing for an additional liver value. Patients are advised to discontinue VEOZAH immediately and seek medical attention including hepatic laboratory tests when signs or symptoms may suggest liver injury, such as new onset fatigue, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or right upper quadrant pain.
Astellas remains dedicated to ensuring VEOZAH is accessible for appropriate patients who may benefit from a non-hormonal treatment option proven to reduce the frequency and severity of moderate to severe vasomotor symptoms (VMS) due to menopause. For all the changes in this label update, please refer to the VEOZAH® U.S. prescribing information."
Approved for the treatment of vasomotor symptoms (VMS) associated with menopause last May, the Astellas Pharma therapy was the first neurokinin 3 receptor antagonist to receive approval for this indication from the FDA. Its approval was supported by clinical efficacy and safety data accrued in the SKYLIGHT trial program, wherein the once-daily, 45 mg pill was assessed in 3000-plus participants for the treatment of VMS.2
At the time of its approval, the FDA issued label warning regarding the risk of elevated hepatic transaminase in patients treated with fezolinetant; the agency advised that eligible patients receive a blood work test to assess for liver damage prior to initiating the therapy, followed by routine bloodwork every 3 months for the 9 months of the regimen.
The FDA additionally discouraged the use of fezolinetant in combination with CYP1A2 inhibitors, as well as in patients with cirrhosis, severe renal damage, or end-stage kidney disease.
Now, this week, the FDA published a Drug Safety Communication stating fezeolinetant’s prescribing information label has been updated to address the risk of liver injury on the basis of post-marketing data showing elevated liver blood test values and signs of liver injury in a patient taking the medication for approximately 40 days.1
“We also added new recommendations for patients and health care 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 wrote. “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.”
Key among the symptoms reported in the patient were abnormal liver enzymes and bilirubin levels, as well as visible signs of liver injury including fatigue, nausea, itching, yellowed eyes and skin, light-colored stool and dark urine. The FDA confirmed the symptoms gradually receded and blood test values improved once the fezolinetant regimen was stopped.
A number of individual demographic and clinical factors may impact one’s risk of liver injury due to fezolinetant, the FDA wrote; as such, the agency cannot determine the likelihood of one experiencing these adverse events due to the therapy. They advised that patients communicate with their prescribing clinicians regarding the benefit – risk profile of fezolinetant. Clinicians are reminded to report adverse events associated with the drug to the FDA’s MedWatch program.
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." See sidebar for the company's full statement.
References
- 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 13, 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
- Petronelli M. FDA approves fezolinetant for vasomotor symptoms. Contemporary OB/GYN. Published May 12, 2023. https://www.contemporaryobgyn.net/view/fda-approves-fezolinetant-for-vasomotor-symptoms
