Drug Interaction Report

MONITOR: Coadministration with weak inducers of CYP450 3A4 may reduce the plasma levels of lazertinib, which is primarily metabolized by the isoenzyme. In a phase 1 study of healthy adult participants, concomitant use of the strong CYP450 3A4 inducer rifampin reduced the peak plasma concentration (Cmax) and systemic exposure (AUC) of lazertinib by 72% and 83%, respectively. Likewise, a pharmacokinetic model predicted that concomitant use with the moderate CYP450 3A4 inducer efavirenz would decrease lazertinib's steady state Cmax and AUC by at least 32% and 44%, respectively. Clinical data with less potent CYP450 3A4 inducers are not available; however, no clinically relevant decrease in lazertinib AUC is expected.

MANAGEMENT: Until more information is available, due to the potential for reduced therapeutic efficacy, caution and monitoring is recommended with concomitant use of lazertinib with weak CYP450 3A4 inducers.

Grapefruit juice may theoretically increase plasma levels of lazertinib, as it does with other drugs metabolized by the CYP450 3A4 enzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. However, the clinical relevance of this potential interaction remains unclear. Studies with strong CYP450 3A4 inhibitors, such as itraconazole, have shown a 1.5-fold increase in the area under the plasma concentration-time curve (AUC) of lazertinib, without any significant changes to the drug's overall safety profile.