Lazertinib

Strong and moderate CYP3A4 inducers: Avoid concomitant use. ( 7.1 )

7.1 Effect of Other Drugs on LAZCLUZE CYP3A4 Inducers Avoid concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4. Lazertinib is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inducer decreased lazertinib concentrations [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of lazertinib.

7.2 Effect of LAZCLUZE on Other Drugs Certain CYP3A4 Substrates Monitor for adverse reactions associated with a CYP3A4 substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 substrate. Lazertinib is a weak CYP3A4 inhibitor. Concomitant use of LAZCLUZE increased concentrations of CYP3A4 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.

Certain BCRP Substrates Monitor for adverse reactions associated with a BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the BCRP substrate. Lazertinib is a BCRP inhibitor. Concomitant use of LAZCLUZE increased concentrations of BCRP substrates [see Clinical Pharmacology (12.3) ], which may increase the risk of adverse reactions related to these substrates.

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , LAZCLUZE can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LAZCLUZE in pregnant women to inform a drug-associated risk. Oral administration of lazertinib to pregnant animals during the period of organogenesis resulted in reduced embryo-fetal survival and fetal body weight in rats and malformations in rabbits at exposures approximately 4 and 0.5 times, respectively, the human exposure at the recommended dose of 240 mg/day based on AUC (see Data ) . Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of 7.5, 30, or 60 mg/kg/day of lazertinib during the period of organogenesis (gestation day 6 to 17). Lazertinib decreased fetal body weights in association with maternal toxicity at 60 mg/kg/day (approximately 4 times the human exposure at the recommended dose of 240 mg/day based on AUC).

In a dose range-finding embryo-fetal development study, oral administration of a higher dose of lazertinib (75 mg/kg/day) to pregnant rats during the period of organogenesis resulted in increased post-implantation loss. In an embryo-fetal development study in rabbits, pregnant animals received oral doses of 5, 25, or 45 mg/kg/day of lazertinib during the period of organogenesis (gestation day 7 to 19).

Lazertinib caused maternal toxicity (reduced body weight and food consumption leading to moribund condition and early termination) and an increase in the incidence of skeletal malformations in the vertebra and skull (fused maxillary process/zygomatic arch) at 45 mg/kg/day (approximately 0.5 times the human exposure at the recommended dose of 240 mg/day based on AUC).