Veozah (Fezolinetant) for Menopausal Hot Flashes
For a menopausal woman with moderate-to-severe hot flashes, prescribe Veozah 45 mg orally once daily, but you must obtain baseline liver function tests (ALT, AST, alkaline phosphatase, total and direct bilirubin) before starting, then monitor monthly for 3 months, and again at 6 and 9 months. 1
Dosing
- Standard dose: 45 mg once daily with or without food 1
- Take at the same time each day
- Swallow whole—do not cut, crush, or chew
- If a dose is missed, take it as soon as possible unless less than 12 hours remain before the next scheduled dose 1
Mandatory Liver Monitoring Protocol
Before starting:
- Do NOT initiate if ALT or AST ≥2× upper limit of normal (ULN) OR total bilirubin ≥2× ULN 1
During treatment:
- Monthly liver function tests for months 1,2, and 3
- Additional tests at months 6 and 9 1
Critical warning: Hepatotoxicity has occurred in postmarketing surveillance, with cases of drug-induced liver injury presenting within 40 days of starting treatment. Patients developed jaundice, elevated transaminases, alkaline phosphatase, and bilirubin 1. This is serious enough to warrant a black box warning from the FDA 1.
When to Stop Immediately
Discontinue Veozah and obtain urgent liver function tests if the patient develops:
- New onset fatigue
- Decreased appetite
- Nausea or vomiting
- Pruritus
- Jaundice
- Pale stools or dark urine
- Abdominal pain 1
Mandatory discontinuation criteria:
- Transaminases >5× ULN, OR
- Transaminases >3× ULN AND total bilirubin >2× ULN 1
If transaminases exceed 3× ULN, increase monitoring frequency until resolution 1.
Contraindications
Do NOT prescribe Veozah if the patient has:
- Known cirrhosis 1
- Severe renal impairment or end-stage renal disease 1
- Concurrent use of CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) 1
Efficacy
Veozah demonstrates robust efficacy for vasomotor symptoms:
- Reduces hot flash frequency by 2.5 episodes per day compared to placebo at 12 weeks 2
- Reduces severity significantly (p<0.001) 2
- Improvement begins within 1 week and is maintained through 52 weeks 2, 3
- Also improves sleep quality, quality of life, depression symptoms, and work productivity 4
The SKYLIGHT trials (1,2, and 4) enrolled over 2,000 women and demonstrated consistent benefit 2, 5, 3.
Common Side Effects
Most frequent adverse events (occurring in 2-8% of patients):
- Upper respiratory tract infection
- Headache
- Back pain
- Diarrhea
- Abdominal pain
- Insomnia
- Arthralgia
- Urinary tract infection 6, 5
Liver enzyme elevations: Occurred in 1.5-2.3% of treated patients in clinical trials, typically asymptomatic and transient, resolving either on treatment or after discontinuation 6. However, postmarketing cases have been more severe 1.
Endometrial and Bone Safety
- Endometrial safety: Meets FDA criteria with hyperplasia rate of 0.5% (upper 95% CI 2.3%), well below the 4% threshold 5
- Bone mineral density: No adverse effects on BMD or trabecular bone score over 52 weeks 5
- No increased risk of benign or malignant neoplasms compared to placebo 6
Clinical Context
When to use Veozah: This is the first FDA-approved non-hormonal neurokinin-3 receptor antagonist for menopausal hot flashes 2, 7. It's particularly valuable for women who:
- Have contraindications to hormone therapy (e.g., breast cancer history—20.5% of real-world users had breast cancer) 8, 9
- Decline hormone therapy due to personal preference 9
- Cannot tolerate SSRIs/SNRIs or gabapentin (the traditional non-hormonal alternatives recommended by guidelines) 10
Important caveat: While older guidelines from 2011-2015 recommend SSRIs/SNRIs or gabapentin as first-line non-hormonal options 10, Veozah was not available at that time. The drug label and recent high-quality trials 2, 5, 3 support its use as a primary non-hormonal option, though the intensive liver monitoring requirement is a practical consideration.
Real-world persistence: Only 20.5% of patients had persistent use (second prescription within 28-90 days), and only 42% of persistent users received the required liver monitoring 8. This highlights the need for robust monitoring systems in your practice.
Storage
Store at room temperature 68-77°F (20-25°C) 1