SUMMARY

• LAZCLUZE (lazertinib) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).¹
• Avoid the concomitant use of LAZCLUZE with strong and moderate cytochrome P450 (CYP) 3A4 (CYP3A4) inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.²
• Lazertinib is a weak CYP3A4 and breast cancer resistance protein (BCRP) inhibitor. Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions.²

PRODUCT LABELING

• LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.
• RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.

CLINICAL STUDIES AND MODEL-INFORMED APPROACHES

Effect of Other Drugs on LAZCLUZE

CYP3A4 Inducers

• Avoid the concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.²
• Lazertinib is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inducer decreased lazertinib concentrations, which may reduce the efficacy of lazertinib.²
  • Concomitant use of rifampin (strong CYP3A4 inducer) with LAZCLUZE decreased lazertinib maximum plasma concentration (C_max) by 72% and area under the concentration-time curve (AUC) by 83%.
  • Concomitant use of efavirenz (moderate CYP3A4 inducer) with LAZCLUZE is predicted to decrease lazertinib steady state C_max by at least 32% and AUC by at least 44%.
  • The effect of concomitant use of weak CYP3A4 inducers on lazertinib C_max or AUC is unknown.

CYP3A4 Inhibitors

• Concomitant use of itraconazole (strong CYP3A4 inhibitor) with LAZCLUZE increased lazertinib C_max by 1.2-fold and AUC by 1.5-fold.³

Gastric Acid-Reducing Agents

• No clinically significant differences in lazertinib C_max and AUC were observed when used concomitantly with gastric acid-reducing agents.⁴

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.²
• Lazertinib is a weak CYP3A4 inhibitor. Concomitant use of LAZCLUZE increased concentrations of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates.²
  • Concomitant use of LAZCLUZE increased midazolam (CYP3A4 substrate) C_max by 1.4-fold and AUC by 1.5-fold.

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.²
• Lazertinib is a BCRP inhibitor. Concomitant use of LAZCLUZE increased concentrations of BCRP substrates, which may increase the risk of adverse reactions related to these substrates.²
  • Concomitant use of LAZCLUZE increased rosuvastatin (BCRP substrate) C_max by 2.2-fold and AUC by 2-fold.
  • No clinically significant differences in the pharmacokinetics of the following were observed or predicted when used concomitantly with lazertinib: metformin (organic cation transporter 1 [OCT1] substrate) or raltegravir (uridine diphosphate glucuronosyltransferase 1A1 [UGT1A1] substrate).

In Vitro Studies

• Lazertinib inhibits CYP3A4, UGT1A1, BCRP, and OCT1. Lazertinib does not induce CYP1A2, CYP2B6, and CYP3A4.²

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 16 August 2024.