The US Food and Drug Administration (FDA) has issued a boxed warning regarding the risk of fezolinetant (Veozah) causing 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, as we have previously seen. 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.
After further discussions with the FDA about the rare, but serious, adverse events related to liver injury, we have added a boxed warning to the U.S. prescribing information about the risk of hepatotoxicity. A boxed warning is used in many situations, including highlighting warning information that is particularly important to the prescriber and patient. In the case of this label update, the prominence of the already available warning on hepatotoxicity has been increased through the boxed warning. Additionally, the postmarketing section (6.2) of the US prescribing information has been updated. For all the changes in this label update, please refer to the December 2024 revised VEOZAH U.S. prescribing information.
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.
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."
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 a 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.
On September 12, 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
Today, the FDA updated the original Drug Safety Communication, stating that a boxed warning has been added to the product label, highlighting the rare occurrence of serious liver injury in patients taking fezolinetant.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.”1
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 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?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
