Drug Interaction Report

Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of lazertinib. To examine this interaction, healthy adult participants (n=16) received lazertinib (160 mg) on day 1, then the potent CYP450 3A4 inhibitor itraconazole (200 mg) daily on days 8 to 16. On day 12, the participants received another single dose of lazertinib (160 mg). Concomitant use of itraconazole increased lazertinib's peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.2- and 1.5-fold, respectively. The clinical significance of these changes is unknown.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.