For what indication is Veozah (fezolinetant) prescribed, and what are its dosing, contraindications, and alternative therapies for menopausal vasomotor symptoms?

Veozah (Fezolinetant) for Moderate-to-Severe Menopausal Vasomotor Symptoms

Veozah (fezolinetant) is FDA-approved for treating moderate-to-severe vasomotor symptoms (hot flashes and night sweats) associated with menopause, offering a nonhormonal alternative for women who cannot or will not use hormone therapy. 1, 2

Mechanism and Indication

• Fezolinetant is a selective neurokinin-3 (NK3) receptor antagonist that blocks neurokinin B binding in the hypothalamus, directly targeting the underlying pathophysiology of menopausal vasomotor symptoms rather than replacing hormones 2, 3
• It is specifically indicated for women experiencing at least 7 moderate-to-severe hot flashes per day who need pharmacologic intervention 1

Dosing and Administration

• Standard dosing is 45 mg once daily, which demonstrated superior efficacy over the 30 mg dose in reducing both frequency and severity of vasomotor symptoms 1
• The 45 mg dose reduced VMS frequency by 2.55 episodes per day at week 4 and 2.53 episodes per day at week 12 compared to placebo 1
• Symptom improvement begins within 1 week and is maintained through at least 52 weeks of continuous treatment 1

Efficacy Profile

• Fezolinetant 45 mg reduces VMS severity scores significantly more than placebo (reduction of 0.29 points at both weeks 4 and 12) 1
• The medication improves menopause-specific quality of life scores, with standardized mean differences of -0.46 at week 4 and -0.37 at week 12 compared to placebo 4
• While hormone therapy remains the most effective treatment (reducing hot flashes by approximately 75%), fezolinetant provides a viable nonhormonal alternative with moderate efficacy 5, 3

Safety and Monitoring Requirements

• Mandatory liver function testing is required: baseline ALT/AST before initiation, then at months 3,6, and 9 after starting treatment 4, 6
• The most common adverse effects are headache (5-10%), fatigue, and arthralgia 4, 2
• Fezolinetant increases risk of ALT or AST elevations >3 times upper limit of normal (RR 2.0), necessitating the monitoring protocol 4
• Serious treatment-emergent adverse events are rare, occurring in only 1% of patients on the 45 mg dose 1

Clinical Positioning and Patient Selection

• Fezolinetant is positioned as first-line therapy for women with contraindications to hormone therapy, including those with history of breast cancer, venous thromboembolism, stroke, or coronary heart disease 7, 5, 6
• Real-world data shows 20.5% of fezolinetant users have a breast cancer diagnosis, highlighting its role in this population where estrogen is contraindicated 6
• It serves as an alternative to SSRIs/SNRIs (venlafaxine, paroxetine) and gabapentin, which are the other recommended nonhormonal first-line options 5, 8

Contraindications and Cautions

• Fezolinetant is contraindicated in women with active liver disease or unexplained persistent elevations in liver transaminases 4
• Use caution in women over age 65, as this population was excluded from randomized trials and real-world safety data is still emerging 6
• The medication requires regular monitoring compliance; real-world data shows only 42% of persistent users received appropriate liver function testing at 3 months, indicating a significant monitoring gap 6

Comparison to Alternative Nonhormonal Therapies

• Unlike SSRIs/SNRIs, fezolinetant has no drug interactions with tamoxifen, making it preferable for breast cancer survivors on endocrine therapy 5, 2
• Compared to gabapentin (which reduces hot flash severity by 46%), fezolinetant offers similar efficacy without sedation or need for bedtime dosing 5, 4
• Venlafaxine reduces hot flash scores by 37-61% depending on dose, comparable to fezolinetant's efficacy profile 5, 8

Persistence and Real-World Utilization

• Only 20.5% of patients demonstrate persistent use (defined as obtaining a second prescription within 28-90 days), suggesting either inadequate response, side effects, or cost barriers 6
• Prescriptions have increased substantially from 233 in the first 3 months post-approval to 1,871 prescriptions in the same period one year later, indicating growing adoption 6

Treatment Algorithm Integration

• For women with contraindications to hormone therapy: Start fezolinetant 45 mg daily after baseline liver function tests, or alternatively use venlafaxine 37.5-75 mg daily or gabapentin 900 mg at bedtime 5, 8, 1
• For breast cancer survivors on tamoxifen: Fezolinetant or gabapentin are preferred over paroxetine due to lack of CYP2D6 inhibition 5, 2
• For women preferring hormone therapy: Transdermal estrogen remains first-line if no contraindications exist and patient is within 10 years of menopause onset and under age 60 7, 5