FDA Raises Red Flag: Popular Menopause Drug Linked to Serious Liver Threats

The U.S. Food and Drug Administration (FDA) recently updated its safety communication regarding Veozah (fezolinetant), a non-hormonal medication that is used to treat menopause-related hot flashes. The alert comes after post-marketing reports indicated a rare but potentially severe risk of liver injury in patients using the drug. As this medication becomes more widely prescribed, the FDA's warning underscores the need for both patients and healthcare professionals to exercise increased caution and adhere to updated monitoring guidelines.

Fezolinetant, marketed under the brand name Veozah, was approved by the FDA in May 2023 to alleviate moderate to severe vasomotor symptoms (VMS)—more commonly known as hot flashes—in menopausal women. It belongs to a class of drugs known as neurokinin 3 (NK3) receptor antagonists. Fezolinetant works by blocking neurokinin B from binding to thermoregulatory neurons, which helps regulate body temperature and reduce hot flashes. However, studies have noted that around 2% of patients experienced liver enzyme elevations that required discontinuation of the drug.¹

Unlike traditional hormonal therapies, Veozah offers a non-hormonal option by targeting receptors in the brain responsible for temperature regulation, thereby mitigating hot flashes.

While its approval was met with enthusiasm for providing a novel treatment option for menopausal symptoms, concerns about its effect on liver health quickly surfaced, prompting the FDA to monitor its safety profile.

On September 12, 2024, the FDA issued a safety communication stating that Veozah, is associated with serious liver threats. This warning comes after a post-marketing case where a patient experienced elevated liver enzyme levels and other signs of liver damage after taking the drug for approximately 40 days, concluding that​ the menopause drug linked to serious liver threats, necessitating regular monitoring and caution.²

Key symptoms associated with liver damage in the patient included:

• Fatigue

• Nausea

• Itching

• Jaundice (yellowing of the skin or eyes)

• Light-colored stools

• Dark urine

• Upper abdominal pain

Once the medication was discontinued, the patient's liver function began to improve, suggesting a direct link between Fezolinetant use and liver injury​.

Given the severity of these findings, the FDA has updated the prescribing information for Veozah to include stricter guidelines on liver monitoring and testing. Both patients and healthcare providers must take these recommendations seriously to mitigate the risk of liver damage. Here's a breakdown of what both parties should do:

For Patients:

• Be Aware of Symptoms: If you are taking Veozah, monitor for any signs of liver issues, including extreme fatigue, nausea, yellowing of the skin or eyes, dark urine, and abdominal pain.

• Stop and Seek Medical Help: Discontinue the medication immediately if any of these symptoms arise and contact your healthcare provider.

• Routine Liver Function Testing: Ensure that your healthcare provider conducts liver function tests before and during treatment. Specifically, testing should occur:

  • Before starting the medication

  • Every month for the first 3 months

  • At months 6 and 9 of treatment​

For Healthcare Providers:

• Liver Function Monitoring: Conduct baseline liver function tests before prescribing fezolinetant and follow the updated testing schedule during treatment.

• Risk Assessment: Evaluate each patient’s risk factors for liver injury, including the use of medications like CYP1A2 inhibitors, which could increase the risk.

• Patient Education: Inform patients about the signs and symptoms of liver injury, and advise them to stop the medication if they experience any of these symptoms.³

The FDA's warning raises important concerns for the treatment of menopause-related symptoms. While hot flashes affect millions of women, especially in the years following menopause, finding a safe and effective treatment remains a challenge. Hormonal therapies have traditionally been the mainstay of treatment, but they come with their own risks, such as increased chances of breast cancer and heart disease.

Fezolinetant, as a non-hormonal alternative, offered a glimmer of hope for women who wanted to avoid hormone-based therapies. However, this new safety information complicates its use, making regular monitoring and patient-provider communication essential to avoid adverse effects.

For many women, hot flashes are more than just an inconvenience; they can significantly affect quality of life. Disruptions in sleep, daily activities, and emotional well-being are common, leading to a strong demand for effective treatments. However, the risk of serious liver injury cannot be ignored, and the FDA’s warning serves as a reminder that even non-hormonal treatments have their own set of risks.

Healthcare providers are now tasked with balancing the benefits of reducing hot flashes against the risks of liver damage. This makes patient education and informed decision-making critical components of any treatment plan involving fezolinetant. For some patients, the relief from hot flashes may outweigh the risks, but this decision should be made carefully and with a full understanding of the potential dangers.³

References:

1. Crespo, Cortney, and Deborah Erlich. "Fezolinetant (Veozah) for the Treatment of Menopause Symptoms." American Family Physician 109, no. 3 (2024): 273-274.

2. Blair, Hannah A. "Fezolinetant in the treatment of vasomotor symptoms associated with menopause: a profile of its use." Drugs & Therapy Perspectives (2024): 1-8.

3. American Pharmaceutical Review. "FDA Adds Warning About Rare Occurrence of Serious Liver Injury with Use of Veozah." American Pharmaceutical Review, September 13, 2024. https://www.americanpharmaceuticalreview.com/Specialty/Microbiology/1315-News/614964-FDA-Adds-Warning-About-Rare-Occurrence-of-Serious-Liver-Injury-With-Use-of-Veozah/.

By Dr. Abhilasha Manker