OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Fezolinetant – Veozah®

DRUG CLASS

Obstetrical and Gynecological Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Fezolinetant	1629229-37-3	C16-H15-FN6-OS

ANNOTATED BIBLIOGRAPHY

References updated: 10 October 2024

Abbreviations: NK3, neurokinin 3.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of NK3 receptor antagonists).
• FDA. Clinical Review. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2023/216578Orig1s000MedR.pdf

  (FDA website with product label and integrated clinical review of data on fezolinetant provided by the sponsor in support of its approval as therapy of the vasomotor symptoms of menopause, mentions that in a pooled analysis of 3 randomized, placebo controlled trials, serum aminotransferase elevations above 3 times the upper limit of normal [ULN] occurred in 2.3% of fezolinetant- [n=1100] vs 0.9% of placebo-recipients [n=952], but that no patient developed liver injury with jaundice, and the abnormalities resolved with dose interruption or discontinuation. Nevertheless, the FDA recommended a warning about drug induced liver injury and monitoring of liver tests during therapy).
• Depypere H, Timmerman D, Donders G, Sieprath P, Ramael S, Combalbert J, Hoveyda HR, et al. Treatment of menopausal vasomotor symptoms with fezolinetant, a neurokinin 3 receptor antagonist: a phase 2a trial. J Clin Endocrinol Metab. 2019;104:5893-5905. [PubMed: 31415087]

  (Among 87 women with vasomotor symptoms due to menopause treated with fezolinetant [90 mg] or placebo twice daily for 12 weeks, the frequency and severity of vasomotor symptoms decreased with fezolinetant treatment within 1-2 weeks and relapsed at a similar rate upon stopping, while adverse event rates were similar in the two groups except for gastrointestinal complaints [14% vs none] and ALT elevations [11% vs 2%], all of the latter being transient, less than 3 times ULN, and not requiring dose adjustment or discontinuation).
• Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N, Lee M, Skillern L, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020;27:382-392. [PMC free article: PMC7147405] [PubMed: 32102086]

  (Among 352 women with moderate-to-severe vasomotor symptoms due to menopause treated with varying doses of fezolinetant [15 to 90 mg twice daily or 30 to 120 mg once daily] or placebo for 12 weeks, vasomotor symptoms were reduced in frequency and severity with all regimens compared to placebo, and total adverse event rates were similar, but ALT or AST elevations arose in 9 [3%] patients on fezolinetant and were above 8 times ULN in 3 who were receiving 60 mg or more daily; all abnormalities resolved once drug was stopped and there were no ALT elevations accompanied by jaundice).
• Fraser GL, Obermayer-Pietsch B, Laven J, Griesinger G, Pintiaux A, Timmerman D, Fauser BCJM, et al. Randomized controlled trial of neurokinin 3 receptor antagonist fezolinetant for treatment of polycystic ovary syndrome. J Clin Endocrinol Metab. 2021;106:e3519-e3532. [PMC free article: PMC8372662] [PubMed: 34000049]

  (Among 73 women with polycystic ovary syndrome treated with fezolinetant [60 or 180 mg] or placebo once daily for 12 weeks, FSH and LH levels were suppressed in a dose-dependent manner with fezolinetant and therapy was well tolerated, there were “no clinically relevant changes in clinical laboratory parameters” and “treatment-emergent ALT increases…were equally distributed over the treatment groups”, only one fezolinetant treated patient had an ALT elevation above 3 times ULN and it resolved spontaneously without dose adjustment).
• Neal-Perry G, Cano A, Lederman S, Nappi RE, Santoro N, Wolfman W, English M, et al. Safety of fezolinetant for vasomotor symptoms associated with menopause: a randomized controlled trial. Obstet Gynecol. 2023;141:737-747. [PMC free article: PMC10026946] [PubMed: 36897180]

  (Among 1830 women with vasomotor symptoms due to menopause treated with fezolinetant [30 or 45 mg] or placebo once daily for 52 weeks, total and severe adverse event rates were similar in the 3 groups as were discontinuations for adverse events; ALT and AST elevations of greater than 3 times ULN were uncommon [1.4% and 2.0% vs 1.0%], and no patient developed clinically apparent liver injury with jaundice).
• Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102. [PubMed: 36924778]

  (Among 527 women with moderate-to-severe vasomotor symptoms due to menopause treated with fezolinetant [30 or 45 mg] or placebo once daily for 12 weeks, followed by an extension study in which all received fezolinetant, improvements in frequency and severity of vasomotor symptoms were greater with fezolinetant, arising within 1 week of starting and maintained for 52 weeks, while adverse events were similar in the 3 groups, ALT elevations during the 12 week period arose in 4 [2.3%] patients on placebo and 4 [1.1%] on fezolinetant, which were above 3 times ULN in 0.6% of both groups).
• Fezolinetant (Veozah) for menopausal vasomotor symptoms. Med Lett Drugs Ther. 2023;65:97-99. [PubMed: 37339088]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of fezolinetant, mentions that therapy can cause serum aminotransferase elevations and patients should be monitored for liver function and injury tests at baseline and at regular times thereafter).
• Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M, Stute P, Thurston RC, 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;108:1981-1997. [PMC free article: PMC10348473] [PubMed: 36734148]

  (Among 501 women with moderate-to-severe vasomotor symptoms due to menopause treated with fezolinetant [30 or 45 mg] or placebo once daily for 12 weeks and then continued on either 30 or 45 mg of fezolinetant, treatment led to a rapid decrease in frequency and severity of vasomotor symptoms which was maintained during extended therapy, and ALT elevations above 3 times ULN arose in 5 [1.5%] on fezolinetant and 1 [0.6%] on placebo, but all abnormalities resolved and there were no instances of clinically apparent liver injury with jaundice).
• Lee A. Fezolinetant: first approval. Drugs. 2023;83:1137-1141. [PubMed: 37462862]

  (Summary of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of fezolinetant shortly after its approval in the US, mentions that total and serious adverse event rates were similar in fezolinetant- and placebo-treated subjects and that adverse events more frequent with fezolinetant included abdominal pain [4.3% vs 2.1%], diarrhea [3.9% vs 2.6%], insomnia [3.9% vs 1.8%], back pain [3.0% vs 2.1%], hot flush [2.5% vs 1.6%], and serum aminotransferase elevations [2.3% vs 0.8%]).
• Drugs for menopausal symptoms. Med Lett Drugs Ther. 2024;66:33-38. [PubMed: 38412276]

  (Concise review of drugs that are approved for therapy of genitourinary and vasomotor symptoms related to menopause, briefly discusses fezolinetant, a nonhormonal therapy for vasomotor symptoms, which can cause adverse events such as abdominal pain, diarrhea, insomnia, back pain, and hepatic aminotransferase elevations).
• Rani P, Zehra D, Mansoor M, Rani P. FDA approved fezolinetant (Veozah): a critical evaluation of its efficacy and safety for menopausal vasomotor symptoms, calling for prospective research. Arch Womens Ment Health. 2024. Epub ahead of print. [PubMed: 38478035]

  (Short review of the data on efficacy and safety of fezolinetant that supported the FDA decision for its approval as therapy of women with moderate-to-severe vasomotor symptoms due to menopause, mentions that serum aminotransferase elevations arose in a small proportion of treated patients [2.3%] but there were no cases of liver injury with jaundice).