Is there a washout between hormone therapy and fezolinetant?

Published

Prescribing Information including BOXED WARNING

In an ongoing real-world Phase 4 study of nonhormonal therapy including fezolinetant, a washout period for hormone therapy of ≥ 10 days is required. In Phase 3 registration trials, washout periods for hormone therapy ranged from one week to six months, dependent on formulation

Use of washout periods (if any) and their duration is subject to the clinical judgement of the healthcare professional.

Women were excluded from the Phase 3 trials SKYLIGHT 1, 2 and 4^1–3 if they used hormonal medications or were not willing to washout and discontinue their use.⁴ The length of time for washout of certain prohibited medications was to be determined by the opinion of the investigator and ranged from one week to six months, dependent on formulation⁴
The washout period for women who were taking hormone therapy prior to entering was dependent on the formulation.⁴ The minimum washout periods per formulation were:
- ≥ one week for vaginal hormonal products (rings, creams, gels, inserts)
- ≥ four weeks for transdermal estrogen alone or estrogen/progestin products
- ≥ eight weeks for prior oral estrogen and/or progestin therapy
- ≥ eight weeks for intrauterine progestin therapy
- ≥ three months for progestin implants and estrogen alone injectable drug therapy
- ≥ six months for prior estrogen pellet therapy or progestin injectable drug therapy
There is an ongoing real-world Phase 4 study, OPTION-VMS, to assess the change from baseline in vasomotor symptom bother in women initiating nonhormonal therapy, including fezolinetant.^5,6 Although women taking hormonal contraceptives or other systemic hormone therapy, including estrogen, progesterone and/or testosterone preparations, are excluded, vaginal or local estrogen preparations and levonorgestrel-releasing intrauterine system are not prohibited⁴
- Intramuscular estradiol must not be given within eight weeks of screening
- Hormone pellet therapy must not be given within six months of screening
- A washout period of ≥ 10 days is required for a restart or switch of a previous therapy

Lederman S, Ottery FD, Cano A, 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(10382):1091-1102. Available at: https://doi.org/10.1016/s0140-6736(23)00085-5.
Johnson KA, Martin N, Nappi RE, 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(8):1981-1997. Available at: https://doi.org/10.1210/clinem/dgad058.
Neal-Perry G, Cano A, Lederman S, et al. Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause. Obstet. Gynecol. 2023;141(4):737-747. Available at: https://doi.org/10.1097/aog.0000000000005114.
Data on file.
Neal-Perry G, Lederman S, Mancuso S, et al. OPTION-VMS: Preliminary Analysis of a Phase IV Observational, Real-World Study of Non-hormonal Pharmacotherapies for Bothersome Menopause-Associated Vasomotor Symptoms [poster]. Orlando, FL, USA. The Menopause Society (TMS) 2025 Annual Meeting; 2025.
Maki PM, Mancuso S, Helbing M, et al. Preliminary Analysis of Work Productivity Outcomes in OPTION-VMS: A Phase IV Observational, Real-World Study of Non-hormonal Treatment for Bothersome Menopause-Associated Vasomotor Symptoms [poster]. Orlando, FL, USA. The Menopause Society (TMS) 2025 Annual Meeting; 2025.