Can I use Veozah (generic name) with mild hypertransaminasemia (elevated liver enzymes)?

Veozah Use with Mild Liver Enzyme Elevations

Veozah should not be initiated if ALT or AST is ≥ 2x ULN (upper limit of normal) or if total bilirubin is ≥ 2x ULN, but can be used with mild liver enzyme elevations that are < 2x ULN with careful monitoring. 1

FDA Recommendations for Veozah and Liver Function

Veozah (fezolinetant) has specific FDA guidelines regarding liver function:

• Baseline assessment: Perform baseline hepatic laboratory tests including ALT, AST, alkaline phosphatase, and bilirubin (total and direct) prior to starting Veozah 1
• Contraindications: Do not start Veozah if:
  • ALT or AST is ≥ 2x ULN
  • Total bilirubin is ≥ 2x ULN
  • Known cirrhosis 1
• Monitoring schedule: If Veozah is initiated, perform follow-up hepatic laboratory tests:
  • Monthly for the first 3 months
  • At 6 months
  • At 9 months after initiation 1

Risk of Hepatotoxicity with Veozah

Clinical trials have shown that Veozah can cause liver enzyme elevations:

• 2.3% of women receiving Veozah experienced ALT/AST elevations >3x ULN compared to 0.9% on placebo 1
• Post-marketing cases of drug-induced liver injury have been reported within 40 days of starting Veozah, with symptoms including fatigue, nausea, pruritus, jaundice, pale feces, and dark urine 1

Management Algorithm for Patients with Elevated Liver Enzymes

1. Assess baseline liver function:

   • Measure ALT, AST, alkaline phosphatase, and bilirubin (total and direct)
   • Determine the degree of elevation

2. Decision pathway:

   • If ALT/AST < 2x ULN and bilirubin normal: May initiate Veozah with monitoring
   • If ALT/AST ≥ 2x ULN or bilirubin ≥ 2x ULN: Do not start Veozah 1

3. During treatment monitoring:

   • Follow the recommended monitoring schedule
   • Discontinue Veozah if:
     • Transaminase elevations > 5x ULN
     • Transaminase elevations > 3x ULN and total bilirubin > 2x ULN 1
   • If transaminase elevations > 3x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution 1

4. Patient education:

   • Advise patients to discontinue Veozah immediately and seek medical attention if they experience signs or symptoms of liver injury:
     • New onset fatigue, decreased appetite, nausea, vomiting
     • Pruritus, jaundice, pale feces, dark urine, or abdominal pain 1

Clinical Considerations

• Transaminase elevations in clinical trials were generally asymptomatic and returned to pretreatment levels without sequelae with dose continuation, interruption, or discontinuation 1

• While some medications may be used with caution in patients with elevated liver enzymes (as seen with methotrexate in inflammatory skin diseases 2), the FDA label for Veozah specifically contraindicates its use when ALT/AST ≥ 2x ULN

• For context, mild transaminase elevations (< 2x ULN) are common and may have various causes including non-alcoholic fatty liver disease, alcohol consumption, or medication effects 3

Conclusion

For patients with mild liver enzyme elevations (< 2x ULN), Veozah can be initiated with careful monitoring according to the FDA-recommended schedule. However, Veozah is contraindicated if liver enzymes are ≥ 2x ULN or if the patient has cirrhosis. Close monitoring and patient education about potential signs of liver injury are essential components of safe Veozah use.