Drug interactions of Repotrectinib

1. Effects of Other Drugs on Repotrectinib

Strong and Moderate CYP3A Inhibitors

Avoid concomitant use with strong or moderate CYP3A inhibitors. Concomitant use of  Repotrectinib with a strong or a moderate CYP3A inhibitor may increase repotrectinib exposure,  which may increase the incidence and severity of adverse reactions of Repotrectinib. Discontinue CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor prior to initiating  Repotrectinib.  

P-gp Inhibitors

Avoid concomitant use with P-gp inhibitors. Concomitant use of Repotrectinib with a P-gp inhibitor may increase repotrectinib exposure, which may increase the incidence and severity of adverse  reactions of Repotrectinib.  

Strong and Moderate CYP3A Inducers 

Avoid concomitant use with strong or moderate CYP3A inducers. Concomitant use of Repotrectinib with a strong or moderate CYP3A inducer may decrease repotrectinib plasma concentrations, which may decrease efficacy of Repotrectinib.  

2. Effects of Repotrectinib on Other Drugs

Certain CYP3A4 Substrates

Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A  substrates, where minimal concentration changes can cause reduced efficacy. If concomitant use  is unavoidable, increase the CYP3A4 substrate dosage in accordance with approved product labeling.

Repotrectinib is a CYP3A4 inducer. Concomitant use of repotrectinib decreases the concentration of CYP3A4 substrates, which can reduce the efficacy of these  substrates.

Contraceptives

Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an  extent that could reduce the effectiveness of hormonal contraceptives.

Avoid concomitant use of Repotrectinib with hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.

from FDA，2023.11