Although there is no available data on larotrectinib use in pregnant women, based on literature reports in human subjects with congenital mutations leading to changes in TRK signaling, findings from animal studies, and the agent's mechanism of action it is believed that larotrectinib can cause embryo-fetal harm when administered to a pregnant woman.^L49816 Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.^L49816 Furthermore, animal studies have revealed that lacrotrectinib can cross the placenta.^L49816 Advise pregnant women of the potential risk to a fetus.^L49816

Female patients of reproductive potential who are being treated with larotrectinib are advised to use effective contraception during larotrectinib treatment and for at least one week after the final dose.^L49816 Males with female partners of reproductive potential are also advised to use effective contraception during larotrectinib therapy and for one week after the final dose.^L49816

Carcinogenicity studies have not been conducted with larotrectinib.^L49816 Larotrectinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assays, with or without metabolic activation, or in the in vitro mammalian mutagenesis assays, with or without metabolic activation.^L49816 In vivo, larotrectinib was negative in the mouse micronucleus test.^L49816