Summary

Impairment of Fertility

• Female rats were treated with oral doses of 3.5, 10.5, 21 or 42 mg/kg/day lumateperone (free base) (0.8, 2.4, 4.9, and 9.7 times the maximum recommended human dose [MRHD] on a mg/m² basis) prior to mating and continuing through conception and implantation.¹
  • Estrus cycle irregularities were observed at doses ≥10.5 mg/kg/day.
  • Decreases in the median number of corpora lutea and implantation sites, and increases in the number of non-gravid uteruses, were recorded at 42 mg/kg/day.
  • Decreased gestation body weight and body weight gain, and increases in time to mating, were observed at 21 and 42 mg/kg/day.
• Male rats were treated with oral doses of 3.5, 10.5, 21 or 42 mg/kg/day lumateperone (0.8, 2.4, 4.9, and 9.7 times the MRHD on a mg/m² basis) for 9 weeks prior to mating and throughout 14 days of mating.¹ 
  • Decreased sperm motility, changes in sperm morphology, reduced epididymal counts, and adverse histopathology changes in testes and epididymides were observed at 21 and 42 mg/kg/day.

Infertility

• Based on findings from animal studies, lumateperone may impair male and female fertility.¹

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 02 September 2025.