Decreased thymus weights in high-dose rats without correlating histopathology
“Thymus: Mean absolute and relative thymus weights in HD male and female rats were decreased. The thymus weight changes were not accompanied by correlating histopathology.”
✓ VerifiedFDA multi-discipline review, p. 65Source ↗
Biodistribution & persistence
Extensive tissue distribution; highest in kidney and liver, also lung, adrenal, thyroid, testes, brain, spinal cord
“In a mass-balance study, [35S]nifurtimox was shown to extensively distribute to tissues, with the highest concentrations of radioactivity in the kidneys and liver followed by lung, adrenal and thyroid glands, testes, brain, and spinal cord.”
✓ VerifiedFDA multi-discipline review, p. 46Source ↗
Modality-specific risk
CNS toxicity (seizures) and testicular atrophy/impaired male fertility at near-therapeutic exposures
“In summary, in nonclinical studies nifurtimox was associated with serious toxicities including seizures in rats and dogs and testicular atrophy and impaired fertility in male rats at near therapeutic exposures.”
✓ VerifiedFDA multi-discipline review, p. 47Source ↗