Can fezolinetant be used concomitantly with SSRIs?

Published

Fezolinetant was efficacious with or without concurrent use of selective serotonin reuptake inhibitors (SSRIs) in a pooled analysis of the Phase 3 trials SKYLIGHT 1 and 2, but no safety subgroup analysis was conducted. Fezolinetant is contraindicated in individuals using CYP1A2 inhibitors

  • Fezolinetant is a substrate of CYP1A2. Concomitant use of fezolinetant with drugs that are weak, moderate, or strong CYP1A2 inhibitors, increases the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) of fezolinetant.1
  • The SSRI fluvoxamine is a strong CYP1A2 inhibitor.2

The number of participants with baseline data ia shown.

P values were calculated without multiplicity adjustment.

aFAS: All randomized participants assessed according to the randomization at first dose. Total numbers of participants – placebo: 342, fezolinetant 30 mg: 339, fezolinetant 45 mg: 341.

Adapted from: Santoro NF, Menopause 2024.

  • Any treatment for vasomotor symptoms (VMS; prescription, over the counter or herbal), as well as strong and moderate CYP1A2 inhibitors (including fluvoxamine), were prohibited during the fezolinetant Phase 3 trials.3
  • Overall, the number of individuals using SSRIs in the SKYLIGHT 1, 2 and 4 trials was 74/952 (7.8%) in the placebo group, 86/1103 (7.8%) in the fezolinetant 30 mg group, and 64/1100 (5.8%) in the fezolinetant 45 mg group.3
  • Subgroup analysis of efficacy (reduction in frequency and severity of VMS) based on concurrent use of SSRIs (yes vs no) was performed for the 12-week pooled data full analysis set (FAS) of SKYLIGHT 1 and 2.4

Figure 2. Difference in change from baseline to Week 12 in VMS severity between fezolinetant groups and placebo by concurrent use of SSRIs.4

The number of participants with baseline data is shown.

P values were calculated without multiplicity adjustment.

aFAS: All randomized participants assessed according to the randomization at first dose. Total numbers of participants – placebo: 342, fezolinetant 30 mg: 339, fezolinetant 45 mg: 341.

Adapted from: Santoro NF, Menopause 2024.

  1. VEOZAH [package insert]. Northbrook, IL, USA: Astellas Pharma, Inc. Available at: https://www.astellas.com/us/system/files/veozah_uspi.pdf.

  2. Lexicomp Online. Inhibitors and Inducers of Cytochrome P450 Enzymes (Lexi-Drugs). Available at: https://online.lexi.com/lco/action/home.

  3. Data on file.

  4. Santoro N, Nappi R, Neal-Perry G, et al. Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: Effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2). Menopause. 2024;31(4):247-257. Available at: https://dx.doi.org/10.1097/gme.0000000000002340.

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