What are the precautions for larotinib/larlotinib?

During the clinical studies of Larotrectinib/Larotrectinib, warnings and precautions such as neurotoxicity, hepatotoxicity, and embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Neurotoxicity: In clinical studies, patients receiving larotrectinib experienced neurological adverse reactions of any grade, with most neurological adverse reactions occurring within the first three months of treatment. Grade 3 neurological adverse reactions include delirium, dysarthria, dizziness, gait disturbance, and paresthesia. Neurologic adverse reactions leading to dose adjustment include dizziness, gait disturbance, delirium, memory impairment, and tremor. Inform patients and caregivers of these risks of larotrectinib. If patients experience neurological adverse reactions, advise them not to drive or operate dangerous machinery.

2. Hepatotoxicity: In clinical studies, patients treated with larotrectinib experienced any grade of elevation of transaminase, including elevation of aspartate aminotransferase (AST) andalanine aminotransferase (ALT); the median onset time of AST elevation was 2 months; the median onset time of ALT elevation was 2 months. Monitor liver tests, including ALT and AST, every two weeks during the first month of treatment and monthly thereafter as clinically indicated.

3. Embryo-Fetal toxicity: Based on literature reports on human subjects with congenital mutations that lead to changes in TRK signaling, animal study results, and its mechanism of action, larotrectinib taken by pregnant women can cause fetal damage. Upon maternal exposure, larotrectinib caused approximately 11 and 0.7 times the malformations observed in rats and rabbits, respectively, at the clinical dose of 100 mg twice daily. Inform women of the potential risk to the fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the last dose of larotrectinib.