Does fezolinetant interact with caffeine?

Published

Fezolinetant is contraindicated in individuals using CYP1A2 inhibitors, as they increase the plasma concentration and exposure of fezolinetant; however, the use of caffeine, a weak CYP1A2 inhibitor, was not restricted in Phase 3 clinical trials and baseline use did not impact efficacy or lead to an increase in adverse events

  • In the Phase 3 trials SKYLIGHT 1, 2, and 4, history of average caffeinated beverage intake was collected at baseline screening.1 Information was collected for less than half of participants due to a protocol amendment to start recording caffeinated beverage intake.
    • Efficacy: Caffeine use at baseline did not have an effect on the efficacy of fezolinetant as measured by vasomotor symptom (VMS) frequency and severity among treatment groups at Week 12.2
    • Safety: The number of treatment-emergent adverse events (TEAEs) and serious TEAEs was similar among treatment groups at Week 52 regardless of baseline caffeine use.1

  • Pooled subgroup analyses of efficacy and safety in the SKYLIGHT trials were based on 0 vs > 0 cups of caffeinated beverage intake per day.1,2
  • Efficacy analysis was performed for the 12-week pooled data in SKYLIGHT 1 and 2 in the full analysis set (FAS).

Figure 1. Difference in change from baseline to Week 12 in VMS frequency between fezolinetant groups and placebo by caffeine use at baseline.2

The number of participants with baseline data is shown.

P-values were calculated without multiplicity adjustment.

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

bA total of 17, 17, and 11 participants in the placebo, fezolinetant 30 mg, and fezolinetant 45 mg groups, respectively, had no caffeinated beverage intake data at baseline or any of the visits. If baseline caffeinated beverage intake was missing, but there was at least one caffeinated beverage intake result at any visit, then the missing baseline data were imputed in accordance with the study visit data.

CBI, caffeine baseline intake

Adapted from: Santoro NF, Menopause 2024.

Figure 2. Difference in change from baseline to Week 12 in VMS severity between fezolinetant groups and placebo by caffeine use at baseline.2

The number of participants with baseline data is shown.

P-values were calculated without multiplicity adjustment.

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

bA total of 17, 17, and 11 participants in the placebo, fezolinetant 30 mg, and fezolinetant 45 mg groups, respectively, had no caffeinated beverage intake data at baseline or any of the visits. If baseline caffeinated beverage intake was missing, but there was at least one caffeinated beverage intake result at any visit, then the missing baseline data were imputed in accordance with the study visit data.

CBI, caffeine baseline intake

Adapted from: Santoro NF, Menopause 2024.

  • Safety analysis was performed for the 52-week pooled data in SKYLIGHT 1, 2 and 4.1
    • In the 0 caffeine use subgroup, TEAEs were reported by 56.3%, 57.2% and 58.9% of participants taking placebo, fezolinetant 30 mg and fezolinetant 45 mg, respectively.
    • In the > 0 caffeine use subgroup, TEAEs were reported by 55.1%, 66.7% and 63.6% of participants taking placebo, fezolinetant 30 mg and fezolinetant 45 mg, respectively.
    • The number of serious TEAEs was < 5% in each treatment group regardless of baseline caffeine use (2.8% vs 1.4% for placebo, 3.1% vs 3.8% for fezolinetant 30 mg, and 3.1 vs 4.3% fezolinetant 45 mg, for 0 caffeine use vs > 0 caffeine use at baseline, respectively).

  1. Data on file.

  2. 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://doi.org/10.1097/gme.0000000000002340.

find-my-msl

Find My MSL

Medical Science Liaisons are available to help answer your scientific questions.

submit

Submit an Inquiry

For any medical inquiries, please submit your question online to Astellas Medical Information or call or fax your inquiry.

Astellas Phone: 1-800-727-7003

Fax: 1-877-829-7942

adverse

Report an Adverse Event or Product Complaint

Report adverse events and product complaints to Astellas or FDA MedWatch.

Astellas Phone: 1-800-727-7003

FDA MedWatch: 1-800-FDA-1088

Hours: M–F, 8 AM–4:30 PM (CT)