The Lung Cancer DDI Manager is expanded with a new drug: Repotrectinib! U.S. Food & Drug Administration approved repotrectinib on November 15, 2023 and the EMA on February 1, 2024.

Repotrectinib is an addition to the treatment for ROS1 TKI-naïve and -pretreated adult patients with ROS1-positive locally advanced or metastatic NSCLC and TKI-naïve and -pretreated adult and pediatric patients 12 years and older with NTRK-positive locally advanced or metastatic solid tumors.

Repotrectinib is metabolized by CYP3A4 enzymes and, in vitro, a substrate of P-gp transporter. Also, repotrectinib is a perpetrator of drug-drug interactions (DDIs) due to the moderate inducing effect on CYP3A enzymes. Therefore, repotrectinib has an increased risk of DDIs.

The product information has included some results of DDI studies:

• Coadministration with itraconazole (strong CYP3A4&P-gp inhibitor) increased repotrectinib AUC and Cmax by 5.9-fold and 1.7-fold, respectively.
• Coadministration with rifampin (strong CYP3A4 & P-gp inducer) decreased repotrectinib AUC and Cmax by 92% and 79%, respectively.
• Repotrectinib (moderate CYP3A inducer) decreased midazolam (CYP3A4 substrate) AUC by 69% and midazolam Cmax by 48%.

In addition, many more drugs are metabolized by CYP3A enzymes or induce of inhibit CYP3A4. In the product information is not a complete overview of these drugs. Therefore, we made extrapolations based on the results above for an overview of clinically relevant DDIs with repotrectinib.

For more information about possible DDIs with repotrectinib: Dr. David Burger will attend ELCC (March 20-23, 2024 in Prague) with a poster presentation on the relevant DDIs of repotrectinib with antithrombotic agents.

And make sure to take a look at the Lung Cancer DDI Manager for all clinical relevant DDIs with repotrectinib!