Boxed Warning: USFDA issues most serious warning on menopause medicine

Written By :  Ruchika Sharma
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2024-12-18 06:00 GMT   |   Update On 2024-12-18 10:15 GMT

US Food and Drug Administration (USFDA) has added a boxed Warning highlighting the known risk of rare but serious liver injury associated with use of menopause medicine Veozah (fezolinetant). VEOZAH is a neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.

The warning came after the review of a postmarketing case of serious liver injury in which a patient experienced symptoms of fatigue, nausea, itching, yellow eyes and skin, light-colored stools, and dark urine within 40 days of starting Veozah. The patient’s liver blood test values were elevated, including abnormal liver enzymes and bilirubin levels. After stopping the medicine, the patient’s symptoms gradually went away, and blood test values slowly returned to normal.

USFDA boxed warning said,  

WARNING: RISKS OF HEPATOTOXICITY

Hepatotoxicity has occurred with the use of VEOZAH in the postmarketing setting (5.1).

• Perform hepatic laboratory tests prior to initiation of treatment to evaluate for hepatic function and injury. Do not start VEOZAH if either aminotransferase is ≥ 2 x ULN or if the total bilirubin is ≥ 2 x ULN for the evaluating laboratory.

• Perform follow-up hepatic laboratory testing monthly for the first 3 months, at 6 months, and 9 months of treatment (2.1, 5.1).

• Advise patients to discontinue VEOZAH immediately and seek medical attention including hepatic laboratory tests if they experience signs or symptoms that may suggest liver injury (new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain) (2.1, 5.1).

• Discontinue VEOZAH if transaminase elevations are > 5 x ULN, or if transaminase elevations are > 3 x ULN and the total bilirubin level is > 2 x ULN.

• If transaminase elevations > 3 x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution (5.1)

Veozah (fezolinetant) is a nonhormonal prescription medicine approved in May 2023 to reduce the frequency and severity of moderate to severe hot flashes caused by menopause. The medicine is in a drug class called neurokinin 3 (NK3) receptor antagonists. It works to restore the balance between estrogen hormones and a brain chemical called neurokinin B (NKB) by blocking the activities of the NK3 receptor, which plays a role in the brain’s control of body temperature.

The medicine is available as a tablet in strength 45 mg taken by mouth once daily. 

In September food safety communication, the USFDA warned that Veozah can cause rare but serious liver injury. If there are signs and symptoms suggesting liver injury, stopping the medicine could prevent worsening liver injury and potentially return liver function to normal.  

The administration added a warning about the risk of liver injury to the existing warning about elevated liver blood test values and required liver blood testing in the prescribing information for Veozah. It made this update after reviewing a postmarketing report of a patient with elevated liver blood test values and signs and symptoms of liver injury after taking the medicine for about 40 days. USFDA 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. 

USFDA advised patients to stop taking Veozah immediately and contact health care professional who prescribed the medicine if signs and symptoms that suggest liver problems occur. These include feeling more tired than usual; nausea; vomiting; unusual itching; light-colored stools; yellowing of the eyes or skin, called jaundice; dark urine; swelling in the stomach or belly area, called the abdomen; or pain in the right upper abdomen.

"Your health care professional will do blood tests before starting Veozah and during treatment to check and monitor how well your liver is working. Talk to your health care professional about the risks and benefits of taking Veozah and discuss any questions or concerns you may have, including about possible alternative treatments," USFDA asked patients.

Informing health care professionals, USFDA said, "
Health care professionals should conduct hepatic laboratory testing before prescribing Veozah, then every month for the first three months after patients start treatment, and then at months 6 and 9 of treatment. When prescribing Veozah, inform patients about the risk of elevated liver blood test values that may occur during treatment and the rare but serious risk of liver injury, and advise them of the need for regular liver blood testing. Discuss the signs and symptoms of liver injury and instruct patients to stop Veozah immediately and contact the health care professional who prescribed the medicine if they develop these any time during treatment."
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