Can men use fezolinetant?

Published

Prescribing Information including BOXED WARNING

Fezolinetant is not indicated for use in men

Astellas Pharma Inc. has not conducted any clinical studies evaluating the safety or efficacy of fezolinetant for the treatment of vasomotor symptoms in male patients including patients with cancer or patients taking hormonal treatment for cancer.
Healthy male participants were included in Phase 1 pharmacokinetic (PK) studies to assess the safety and tolerability of fezolinetant following single and multiple ascending oral dose administration.^1,2 These studies suggested fezolinetant was well tolerated but there was lower exposure in males than in females and fezolinetant lowered testosterone levels.
In preclinical animal studies, there was no sex difference in the toxicity profile.²

In a single center, double-blind, randomized, placebo-controlled, three part, single and multiple ascending dose escalation study in healthy male (n = 41) and female (n = 24) participants between 18 and 45 years of age, administration of single and multiple ascending doses up to 180 mg were well tolerated.² When comparing fezolinetant exposure after single dosing or at steady-state in healthy males and females, maximum concentration (C_max) and area under the curve (AUC) exposures were significantly lower in males.² After single and multiple administrations of fezolinetant to healthy males, a dose-dependent decrease in total testosterone, free testosterone (FT), follicle stimulating hormone (FSH), and luteinizing hormone (LH) plasma concentrations was observed compared with placebo.² Fraser, et al. reported FSH levels were not significantly suppressed relative to placebo for any dose cohort, at any time, whereas inhibition of LH and testosterone was significant at various time points.¹ Plasma LH and testosterone returned to baseline levels within 24 hours of dosing.
In a single center, double-blind, randomized, placebo-controlled, three part, single and multiple ascending dose escalation study in healthy male (n = 8) participants (between 18 and 45 years of age) and female (n = 32) participants (between 18 and 59 years of age), administration of single ascending doses up to 900 mg in male and female participants was well tolerated.² Assessment of gender effect showed lower exposure in terms of AUC and C_max in male compared with female participants, and a shorter terminal half-life (t_1/2).² After administration of fezolinetant to healthy males, plasma total testosterone and FT concentrations were decreased, with the minimum concentration C_min (i.e., maximal effect) and AUC comparable after 720 mg and 900 mg fezolinetant, whereas no clear effect was observed after placebo intake. A similar effect was observed for LH.²
In a single center, placebo-controlled, randomized, participant- and investigator-blinded, two part study in healthy Japanese male (n = 28) participants (aged ≥ 20 and < 45 years) and healthy Japanese pre- (n = 8) and postmenopausal (n = 8) female participants (aged ≥ 20 and < 65 years), administration of single and multiple oral doses of fezolinetant was well tolerated.² In postmenopausal females following 180 mg single and multiple dosing daily for 10 days, a higher C_max and AUC and longer t_1/2 were observed compared with males and premenopausal females.² Following a single administration of fezolinetant (15 and 60 mg) and a single and multiple dose administrations of fezolinetant (180 mg) to healthy Japanese males, LH, FSH, total testosterone, and FT concentrations decreased with increased dose of fezolinetant.²
A case report of an 83-year-old man with prostate cancer and refractory VMS following androgen deprivation therapy, reported a profound reduction in the frequency and severity of hot flashes with fezolinetant 45 mg, with no adverse effects.³ His prostate-specific antigen level was unaffected, and no new biochemical derangements were identified, including hepatic dysfunction.

Fraser GL, Ramael S, Hoveyda HR, et al. The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women. J. Clin. Endocrinol. Metab. 2016;101(2):417-426. Available at: https://doi.org/10.1210/jc.2015-3621.
Data on file.
Lin KL, Shekar S, Crumbaker M, Joshua AM. Neurokinin-3 Receptor Antagonism for Refractory Hot Flashes in Men. N. Engl. J. Med. 2025;392(2):202-203. Available at: https://doi.org/10.1056/nejmc2412361.