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fezolinetant (Veozah)

Indications: - vasomotor symptoms of menopause (FDA-approved May 2023) [2] - improvement noted as early as 1 week & sustained through 40 weeks [3] - effective in reducing moderate-to-severe vasomotor symptoms of menopause & sleep disturbances in postmenopausal women [4] - 30mg & 45mg fezolinetant improved menopausal quality of life at 12 weeks [5] Contraindications: - cirrhosis - chronic renal failure (severe) Dosage: - once or twice daily oral, 30 mg, 45 mg approved dose Monitor: - liver function tests at baseline & every 3 months for >= 9 months [3] - stop if serum transaminases exceed 5 times the upper limit of normal or if serum transaminases exceed 3 times the upper limit of normal & total serum bilirubin is > 2 times the upper limit of normal - more frequent liver function testing if the serum transaminases exceed 3 times the upper limit of normal, but the total serum bilirubin is < 2 times the upper limit of normal Adverse effects: - well tolerated during 52 weeks of follow up - headache most common adverse effect [3] - hepatotoxicity - elevations in serum transaminases >= 3X upper limit of normal (< 2%) [3] - resolution with termination of treatment Mechanism of action: - neurokinin-3 receptor antagonist Notes: - list price 2023 $550/month [3]

General

endocrine agent receptor antagonist

Database Correlations

PUBCHEM cid=117604931

References

  1. Fraser GL, Lederman S, Waldbaum A et al. A phase 2b, randomized, placebo-controlled, double-blind, ose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause 2020 Apr; 27:382 PMID: 32102086 Free PMC Article https://journals.lww.com/menopausejournal/FullText/2020/04000/A_phase_2b,_randomized,_placebo_controlled,.4.aspx
  2. Splete H FDA OKs New Drug for Hot Flashes Medscape. May 12, 2023 https://www.medscape.com/viewarticle/991897
  3. O'Dwyer MC New Nonhormonal Option for Vasomotor Symptoms of Menopause NEJM Journal Watch. June 15, 2023 (subscription needed) - Lederman S et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): A phase 3 randomised controlled study. Lancet 2023 Apr 1; 401:1091. PMID: 36924778 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00085-5/fulltext - Johnson KA et al. Efficacy and safety of fezolinetant in moderate to severe vasomotor symptoms associated with menopause: A phase 3 RCT. J Clin Endocrinol Metab 2023 Feb 3; [e-pub]. PMID: 36734148 https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad058/7025342 - Neal-Perry G et al. Safety of fezolinetant for vasomotor symptoms associated with menopause: A randomized controlled trial. Obstet Gynecol 2023 Apr; 141:737. PMID: 36897180 PMCID: PMC10026946 Free PMC article https://journals.lww.com/greenjournal/Fulltext/2023/04000/Safety_of_Fezolinetant_for_Vasomotor_Symptoms.13.aspx
  4. Bonga KN, Mishra A, Maiti R et al Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis. Obstet Gynecol. 2024 Jan 16. PMID: 38227939
  5. Cano A, Nappi RE, Santoro N, et al. Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials. BJOG. 2024 Feb 6 PMID: 38320967 Free article
  6. Monaco K FDA Warning on Hot Flash Drug. Clinicians should perform liver blood tests before and during Veozah treatment. MedPage Today September 12, 2024 https://www.medpagetoday.com/obgyn/menopause/111922 - FDA Drug Safety Communication. Sept 12, 2024 FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause. Stop medicine if signs and symptoms of liver injury occur https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-warning-about-rare-occurrence-serious-liver-injury-use-veozah-fezolinetant-hot-flashes-due