Effect of Other Drugs on Repotrectinib

Release date: 2026-06-05 13:36:42     Recommended: 5

Effect of Other Drugs on Repotrectinib

Avoid concomitant use of repotrectinib with P-glycoprotein inhibitors, strong or moderate CYP3A inducers, and strong or moderate CYP3A inhibitors. CYP3A enzymes are the primary metabolic pathway for repotrectinib. Concomitant use with strong or moderate CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, etc.) significantly increases repotrectinib plasma concentrations, raising the risk of toxicity. Conversely, strong or moderate CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort, etc.) decrease repotrectinib concentrations, potentially reducing efficacy. Before initiating repotrectinib, discontinue CYP3A inhibitors for at least 3 to 5 half-lives. P-glycoprotein inhibitors may also affect drug distribution.

Effect of Repotrectinib on Other Drugs (CYP3A4 Substrates)

Repotrectinib is a CYP3A4 inducer; concomitant use decreases the concentrations of CYP3A4 substrates, thereby potentially reducing the efficacy of these substrates. Avoid concomitant use of repotrectinib with certain CYP3A4 substrates unless otherwise recommended in the prescribing information for the substrate, particularly those for which a small change in concentration may lead to reduced efficacy (i.e., narrow therapeutic window drugs), such as certain immunosuppressants (cyclosporine, tacrolimus), certain benzodiazepines (midazolam, triazolam), and certain hormonal drugs. If unavoidable, increase the dose of the CYP3A4 substrate appropriately according to the approved prescribing information and monitor for efficacy and adverse reactions.

Interaction Between Repotrectinib and Hormonal Contraceptives

Repotrectinib can significantly reduce exposure to progestins or estrogens to an extent that may reduce the effectiveness of hormonal contraceptives. Therefore, avoid concomitant use of repotrectinib with any hormonal contraceptives (including oral tablets, patches, vaginal rings, implants, intrauterine systems, etc.). For females of reproductive potential, advise use of effective non-hormonal contraception, such as copper intrauterine devices or barrier methods (male or female condoms, cervical caps with spermicide). Patients should fully inform their healthcare provider that they are taking repotrectinib when selecting a contraceptive method to avoid unintended pregnancy. This interaction applies throughout treatment and for 2 months after discontinuation (for females) or 4 months after discontinuation (for males with partners of reproductive potential).