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.

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.