Veozah and the Liver: A Necessary Safety Discussion
Veozah (fezolinetant) is a nonhormonal prescription medication used to treat moderate to severe hot flashes associated with menopause. The FDA has issued a boxed warning for Veozah, indicating a risk of rare but serious liver injury. This warning, along with required regular liver function testing, addresses the potential for Veozah to raise liver enzymes.
What are liver enzymes and why are they important?
Liver enzymes like ALT and AST are vital for liver functions such as metabolism and detoxification. Elevated levels of these enzymes in the blood can signal liver inflammation or damage, making blood tests for these enzymes an indicator of potential liver injury.
Clinical Trial vs. Postmarketing Experience
Clinical trials showed that a small percentage (2.3%) of women taking Veozah experienced elevated liver transaminase levels (ALT and/or AST) more than three times the upper limit of normal, compared to 0.9% on placebo. These elevations were typically without symptoms and normalized even with continued dosing or after stopping the drug. However, postmarketing surveillance has revealed rare but serious cases of drug-induced liver injury, sometimes occurring relatively soon after starting treatment (within 40 days). In these serious cases, liver function improved after discontinuing Veozah.
The FDA's Boxed Warning and Monitoring Protocol
The FDA added a boxed warning to Veozah's prescribing information due to postmarketing reports of severe liver injury. This led to an updated monitoring protocol to help detect potential liver issues early.
FDA-Mandated Monitoring Schedule for Veozah
- Baseline Testing: Liver blood tests (serum ALT, AST, ALP, and total bilirubin) are required before starting Veozah.
- Monthly Monitoring (Months 1-3): Repeat hepatic laboratory tests are needed each month for the first three months of treatment.
- Routine Testing (Months 6 & 9): Further blood tests are required at month 6 and month 9.
- Symptom-Based Testing: If signs or symptoms of liver injury occur at any time, immediate testing is necessary.
Understanding Elevated Liver Enzymes: Mild vs. Serious Injury
There's a distinction between the mild enzyme elevations seen in trials and the more serious liver injury reported after the drug was on the market.
| Characteristic | Mildly Elevated Liver Enzymes | Serious Liver Injury (Hepatotoxicity) |
|---|---|---|
| Incidence | More common (2.3% in trials) | Rare (postmarketing reports) |
| Symptom Profile | Usually asymptomatic | Symptomatic |
| Symptoms | Typically none | Fatigue, nausea, vomiting, itching, jaundice, pale stools, dark urine, abdominal pain |
| Enzyme Levels | Transient, lower elevations (e.g., >3x ULN) | Significantly elevated levels (e.g., >5x ULN or >3x ULN with >2x ULN bilirubin) |
| Action | May continue with monitoring; potential dose interruption | Immediate discontinuation of Veozah |
Signs and Symptoms of Liver Injury to Watch For
Patients taking Veozah should be aware of potential liver injury symptoms and contact a healthcare provider immediately if they occur. Key symptoms include new or increased fatigue, nausea/vomiting, unusual itching, jaundice, dark urine, pale stools, abdominal pain, and decreased appetite.
Conclusion
Veozah, while an option for menopausal hot flashes, carries a risk of elevated liver enzymes and, rarely, serious liver injury. The FDA's boxed warning and required monitoring protocol, including regular liver function tests, are in place to manage this risk. Patient awareness of liver injury symptoms and prompt communication with a healthcare provider are vital for safe use. Veozah is contraindicated in patients with cirrhosis. Consult a healthcare professional or the FDA's resources for complete prescribing information.
