Fetroja: genotox, carcinogenicity and repro: done or skipped?

“non-mutagenic in Ames test, increased chromosomal aberrations in vitro but not considered clastogenic in the in vivo rat micronucleus assay and did not induce DNA damage in the Comet assay in rat hepatocytes”

“Carcinogenicity studies were not conducted. CHMP agreed that carcinogenicity studies were not needed as the SmPC states that the duration of dosing will be generally 14 days or less (not exceeding 21 days).”

“Cefiderocol did not cause developmental toxicity in mice when administered to dams at daily subcutaneous doses up to 2000 mg/kg/day (twice daily 1000 mg/kg doses) from GD 6-15. It did not cause developmental toxicity in rats when administered intravenously to dams at doses up to 1000 mg/kg/day from GD 6-17.”

“Prolongation of the QTc (Bazett) was observed in cynomolgus monkeys following a 1000 mg/kg dose given intravenously over 1 hour (observed in both a single dose safety pharmacology study and in repeat dose toxicology studies).”