From the FDA Drug Label
The no observed adverse effect level (NOAEL) for embryo-fetal development was 50 mg/kg/day in rats and 45 mg/kg/day in rabbits (62- and 16‑fold the human AUC24 at the human therapeutic dose for rats and rabbits, respectively). Fezolinetant showed no effects on fertility and early embryonic development in rats [see Nonclinical Toxicology (13. 1)]. In the pre- and post-natal development study in rats, the NOAEL for maternal and fetal toxicity was 30 mg/kg/day (36‑fold the human AUC24 at the human therapeutic dose) based on delayed parturition and embryo-lethality at 100 mg/kg/day The NOAEL for F1 generation development was determined to be 100 mg/kg/day for females (204-fold the human AUC24 at the human therapeutic dose) and 10 mg/kg/day for males (11-fold the human AUC24 at the human therapeutic dose) The F1 male showed delayed male reproductive maturation, characterized as incomplete balanopreputial separation at time of mating, at doses of greater than or equal to 30 mg/kg/day (36-fold the human AUC24 at the human therapeutic dose), which affected male fertility [see Nonclinical Toxicology (13.1)].
Fezolinetant has been studied in animal models to assess its potential effects on embryo-fetal development, fertility, and early embryonic development. The results indicate that:
- The NOAEL for embryo-fetal development was 50 mg/kg/day in rats and 45 mg/kg/day in rabbits.
- Fezolinetant showed no effects on fertility and early embryonic development in rats.
- The NOAEL for maternal and fetal toxicity was 30 mg/kg/day in rats.
- The NOAEL for F1 generation development was 100 mg/kg/day for females and 10 mg/kg/day for males.
- Delayed male reproductive maturation was observed at doses of greater than or equal to 30 mg/kg/day. 1
From the Research
Fezolinetant is a recommended treatment for moderate to severe vasomotor symptoms associated with menopause, as it has been shown to significantly reduce the frequency and severity of hot flashes in clinical trials, with a standard dosage of 45 mg taken orally once daily with or without food 2. The medication works by blocking neurokinin 3 receptor antagonists in the brain's temperature control center, which helps reduce the frequency and severity of hot flashes. Some key points to consider when prescribing fezolinetant include:
- Common side effects include abdominal pain, diarrhea, insomnia, and elevated liver enzymes
- Patients should undergo liver function testing before starting fezolinetant, and those with liver impairment may require dosage adjustments or should avoid the medication altogether
- The medication should not be used during pregnancy or breastfeeding, and it may interact with certain medications that affect liver enzymes
- Fezolinetant typically begins working within 1-2 weeks, with maximum benefit often seen after 4-8 weeks of consistent use
- Unlike hormone therapy, fezolinetant specifically targets the neurochemical pathway involved in hot flashes without affecting estrogen levels throughout the body The efficacy and safety of fezolinetant have been demonstrated in clinical trials, including a phase 3 randomized controlled study published in the Lancet, which showed that fezolinetant significantly reduced the frequency and severity of vasomotor symptoms compared to placebo 2. Additionally, a study published in The Journal of Clinical Endocrinology and Metabolism found that fezolinetant was efficacious and well-tolerated for treating moderate to severe vasomotor symptoms associated with menopause 3. Overall, fezolinetant is a non-hormonal alternative for women who cannot or prefer not to use hormone therapy for menopausal symptoms, and it has been shown to be effective in reducing the frequency and severity of hot flashes.