Drug interactions of Larotrectinib

1.Effects of Other Drugs on Larotrectinib

Strong and Moderate CYP3A4 Inhibitors

Coadministration of Larotrectinib with a strong or moderate CYP3A4 inhibitor may increase  larotrectinib plasma concentrations, which may result in a higher incidence of adverse reactions. Avoid coadministration of Larotrectinib with strong  CYP3A4 inhibitors, including grapefruit or grapefruit juice. If coadministration of strong  CYP3A4 inhibitors cannot be avoided, modify Larotrectinib dose as recommended. In patients coadministered a moderate CYP3A4 inhibitor with  Larotrectinib, monitor for adverse reactions more frequently and reduce the Larotrectinib dosage  based on the severity of emergent adverse reactions. 

Strong and Moderate CYP3A4 Inducers

Coadministration of Larotrectinib with a strong or moderate CYP3A4 inducer may decrease  larotrectinib plasma concentrations, which may decrease the efficacy of Larotrectinib. Avoid coadministration of Larotrectinib with strong CYP3A4  inducers, including St. John’s wort. If coadministration of strong CYP3A4 inducers cannot be  avoided, modify Larotrectinib dose as recommended. For coadministration with moderate  CYP3A4 inducers, modify Larotrectinib dose as recommended.

2.Effects of Larotrectinib on Other Drugs

Sensitive CYP3A4 Substrates

Coadministration of Larotrectinib with sensitive CYP3A4 substrates may increase their plasma  concentrations, which may increase the incidence or severity of adverse reactions. Avoid coadministration of Larotrectinib with sensitive CYP3A4  substrates. If coadministration of these sensitive CYP3A4 substrates cannot be avoided, monitor  patients for increased adverse reactions of these drugs.  

from FDA，2022.11