On December 16, 2024, the U.S. Food and Drug Administration (FDA) issued a new boxed warning for fezolinetant (Veozah) to emphasize its potential to cause unusual liver injury. This was after the FDA had investigated a post-marketing report on a serious case of liver damage. This involves a patient who developed symptoms within 40 days after initiating this drug therapy. These symptoms are fatigue, nausea, changes in the color of the urine and the stools, and changes in the color of the eyes and the skin.
The blood test indicated elevated levels of bilirubin and serum liver enzymes that signified liver damage. The patient’s symptoms were reported to have improved, and the liver functions normalized once the patient stopped the medication. The FDA determined that the hepatic injury was due to fezolinetant.
Despite the significant risk, the drug manufacturer of Veozah, Astellas Pharma, is confident about the general benefits of the medication for the patients and the medical professionals. “The company stated that the complete risk-benefit profile of Veozah remains positive and unchanged. They emphasized the importance of ensuring that medical practitioners and patients are informed about the side effects and the necessity of liver testing.”
Astellas reaffirmed its confidence in Veozah, highlighting its safety profile as one of the major advantages in addressing menopause-related vasomotor symptoms (VMS) and establishing it as a nonhormonal, effective treatment for modest to acute cases.
Fezolinetant approved on May 12, 2023, is the first neurokinin 3 receptor (NK3R) antagonist, approved for managing VMS related to menopause. These symptoms are often called hot flashes; this sensation is very distressing and largely impairs the quality of life. More than 3000 patients took part within the United States, Europe, and Canada participated in phase 3 clinical trials known as BRIGHT SKY™.
Data extracted throughout these two SKYLIGHT 1™ and SKYLIGHT 2™ studies provided evidence of safety coupled with efficacy for the medication involved in these studies, whereas those findings from the SKYLIGHT 4™ study demonstrated safety with the drug in its use over an extended time duration.
However, the original fezolinetant labels indicated the potential side effects that included high levels of liver enzymes. Pre-treatment liver function assessment at regular intervals throughout the nine months of treatment was recommended for the patients. The FDA later found that the drug had restricted fezolinetant in patients with severe liver or kidney disorders and was not to be taken in conjunction with other prescription drugs.
Further actions took place earlier in 2024 concerning liver safety. On September 12, the agency expanded the alert to possible liver damage and recommended that the drug should be discontinued immediately if signs of liver impairment appeared. In recent years, the risk has been compounded by the newly added boxed warning where the FDA’s strongest warning resides.
The FDA advises patients to discontinue their medication and seek the attention of their healthcare provider once symptoms of liver problems occur, like fatigue, itching, light-colored stools, eyes and body yellowing, and dark-colored urine.
Healthcare professionals are advised to carry out a range of comprehensive liver function tests before initiating fezolinetant treatment. Among such tests, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, and direct bilirubin levels must be included.
Such professionals are recommended not to prescribe the medication if any of the values are more than double the normal limit. For the initial 3 months, the common advisory given is to take monthly liver function tests followed by tests in the sixth and ninth months.
If the liver enzymes are above 5 times the limit or both liver enzymes and bilirubin levels have risen substantially, the health care provider should immediately withdraw the drug.
The decision of the FDA involves the safety aspect of the patients, but it also recognizes the importance of fezolinetant in managing menopausal symptoms. Patients and providers are kept alert, and they must assess the benefits of the treatment for risks that may be encountered. When the usage of this medication is complemented with the new safety guidelines, it can help to avoid complications.
Reference: Abigail Brooks. FDA Adds Boxed Warning to Fezolinetant (Veozah) for Liver Injury Risk. HCP Live. December 17, 2024. Accessed from FDA Adds Boxed Warning to Fezolinetant (Veozah) for Liver Injury Risk
