Is E sometime Elinzanetant (generic name) better than Veozah (generic name) for pain management in a patient with a chronic condition and potential history of adverse reactions to similar medications?

Elinzanetant vs Veozah for Vasomotor Symptoms

Elinzanetant appears to be the superior choice over Veozah (fezolinetant) based on comparable efficacy for vasomotor symptoms but a significantly safer hepatic profile, as Veozah carries an FDA boxed warning for serious hepatotoxicity while elinzanetant has not demonstrated hepatotoxic effects in clinical trials. 1, 2

Critical Safety Distinction

Veozah has documented serious hepatotoxicity risk that fundamentally limits its use:

• The FDA label includes a boxed warning for hepatic transaminase elevation and hepatotoxicity 1
• Postmarketing cases showed drug-induced liver injury with transaminases up to 50x ULN, alkaline phosphatase up to 4x ULN, and bilirubin up to 5x ULN within 40 days of starting treatment 1
• Patients experienced fatigue, nausea, pruritus, jaundice, pale feces, and dark urine requiring immediate discontinuation 1
• Mandatory baseline hepatic function tests (ALT, AST, ALP, total and direct bilirubin) are required before initiation 1
• Monthly monitoring is required for the first 3 months, then at 6 and 9 months 1
• Veozah cannot be started if ALT or AST ≥2x ULN or total bilirubin ≥2x ULN 1

In contrast, elinzanetant demonstrated no hepatotoxic effects:

• The 52-week OASIS-3 trial specifically noted that elinzanetant was not associated with hepatotoxic effects 2
• No hepatic monitoring requirements have been established for elinzanetant 2

Comparative Efficacy Data

Both medications demonstrate similar efficacy for vasomotor symptoms, making safety the deciding factor:

Elinzanetant (OASIS trials):

• At week 4: reduced VMS frequency by 3.0-3.3 episodes vs placebo (P<0.001) 3
• At week 12: reduced VMS frequency by 3.2 episodes vs placebo (P<0.001) 3
• Improved VMS severity by 0.2-0.3 points at week 4 and 0.3-0.4 points at week 12 (P<0.001) 3
• 52-week data showed sustained efficacy with least-squares mean difference of -1.6 episodes at week 12 (P<0.001) 2

Veozah efficacy (from FDA approval):

• Approved for moderate to severe VMS due to menopause 4
• Demonstrated efficacy in reducing frequency and severity of VMS 4
• Specific comparative efficacy data not provided in available evidence

Adverse Event Profile

Elinzanetant has a more favorable overall safety profile:

• Most common treatment-related adverse events: somnolence, fatigue, and headache (30.4% vs 14.6% placebo) 2
• No endometrial hyperplasia or meaningful changes in bone density or bone turnover markers 2
• Serious adverse events occurred in only 2.5% during weeks 1-12 2

Veozah adverse reactions (≥2% and greater than placebo):

• Abdominal pain (4.3% vs 2.1%) 1
• Diarrhea (3.9% vs 2.6%) 1
• Insomnia (3.9% vs 1.8%) 1
• Back pain (3.0% vs 2.1%) 1
• Hot flush (2.5% vs 1.6%) 1
• Hepatic transaminase elevation (2.3% vs 0.8%) 1

Special Population Considerations

Elinzanetant has demonstrated efficacy in breast cancer patients receiving endocrine therapy:

• Phase 3 trial (OASIS-4) showed reduction of 3.5 episodes at week 4 and 3.4 episodes at week 12 vs placebo (P<0.001) in women with HR-positive breast cancer 5
• This represents an important advantage for patients who cannot use hormonal therapy 5

Clinical Implementation Algorithm

For patients requiring treatment of moderate to severe vasomotor symptoms:

1. First-line choice: Elinzanetant 120 mg once daily 3, 2

   • No baseline hepatic monitoring required
   • Rapid onset of action (significant improvement by week 4)
   • Sustained efficacy through 52 weeks

2. Veozah should only be considered if:

   • Elinzanetant is unavailable or contraindicated
   • Patient has normal baseline hepatic function (ALT/AST <2x ULN, bilirubin <2x ULN) 1
   • Patient can comply with intensive hepatic monitoring schedule 1
   • Patient understands and accepts risk of serious hepatotoxicity 1

3. If Veozah is used, mandatory monitoring includes:

   • Baseline: ALT, AST, ALP, total and direct bilirubin 1
   • Monthly for first 3 months, then at 6 and 9 months 1
   • Immediate discontinuation if transaminases >5x ULN or >3x ULN with bilirubin >2x ULN 1

Common Pitfalls to Avoid

• Do not initiate Veozah without baseline hepatic function tests - this is an FDA requirement that cannot be bypassed 1
• Do not continue Veozah if patients develop new fatigue, nausea, pruritus, jaundice, pale feces, dark urine, or abdominal pain - these are warning signs of hepatotoxicity requiring immediate discontinuation and hepatic testing 1
• Do not use Veozah in patients taking CYP1A2 inhibitors - this is an absolute contraindication 1
• Do not assume both medications have equivalent safety profiles - the hepatotoxicity risk with Veozah is a critical distinguishing factor 1, 2