LAZERTINIB Drug Interactions: What You Need to Know

INTERACTIONS 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>, which may increase the risk of adverse reactions related to these substrates.

None. None. ( 4 )

AND PRECAUTIONS Venous Thromboembolic Events (VTE): Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as medically appropriate. Withhold LAZCLUZE and amivantamab based on severity. Once anticoagulant treatment has been initiated, resume LAZCLUZE and amivantamab at the same dose at the discretion of the healthcare provider. Permanently discontinue amivantamab and continue LAZCLUZE for recurrent VTE despite therapeutic anticoagulation. ( 2.3 , 2.4 , 5.1 )

Interstitial Lung

Disease (ILD)/Pneumonitis : Monitor for new or worsening symptoms indicative of ILD/pneumonitis. Withhold LAZCLUZE and amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. ( 2.4 , 5.2 )

Dermatologic Adverse

Reactions : Can cause severe rash including acneiform dermatitis. At treatment initiation, prophylactic and concomitant medications are recommended. Withhold, reduce the dose or permanently discontinue LAZCLUZE and amivantamab based on severity. ( 2.3 , 2.4 , 5.3 )

Ocular Adverse

Reactions : Promptly refer patients with new or worsening signs and symptoms of ocular adverse reactions, including keratitis, to an ophthalmologist for evaluation. Withhold, reduce the dose, or permanently discontinue amivantamab and continue LAZCLUZE based on severity. ( 5.4 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 )

5.1 Venous Thromboembolic Events LAZCLUZE in combination with amivantamab can cause serious and fatal venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). The majority of these events occurred during the first four months of therapy <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In MARIPOSA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> , VTE occurred in 36% of patients receiving LAZCLUZE in combination with amivantamab, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 7% of patients had VTE leading to dose interruptions of LAZCLUZE, 0.5% of patients had VTE leading to dose reductions of LAZCLUZE, and 1.9% of patients permanently discontinued LAZCLUZE due to VTE. The median time to onset of VTEs was 84 days (range: 6 to 777). Administer prophylactic anticoagulation for the first four months of treatment <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> . The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE and treat as medically appropriate. Withhold LAZCLUZE and amivantamab based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span>. Once anticoagulant treatment has been initiated, resume LAZCLUZE and amivantamab at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue amivantamab. Continue treatment with LAZCLUZE at the same dose level at the discretion of the healthcare provider <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . Refer to the amivantamab prescribing information for recommended amivantamab dosage modification.

5.2 Interstitial Lung Disease (ILD)/Pneumonitis LAZCLUZE in combination with amivantamab can cause interstitial lung disease (ILD)/pneumonitis. In MARIPOSA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>, ILD/pneumonitis occurred in 3.1% of patients treated with LAZCLUZE in combination with amivantamab, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued LAZCLUZE and amivantamab due to ILD/pneumonitis <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LAZCLUZE and amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span>.

5.3 Dermatologic Adverse Reactions LAZCLUZE in combination with amivantamab can cause severe rash including dermatitis acneiform, pruritus and dry skin. In MARIPOSA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> , rash occurred in 86% of patients treated with LAZCLUZE in combination with amivantamab, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose reduction of LAZCLUZE occurred in 19% of patients, rash leading to dose interruption of LAZCLUZE occurred in 30% of patients, and LAZCLUZE was permanently discontinued due to rash in 1.7% of patients <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. When initiating treatment with LAZCLUZE in combination with amivantamab, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>. Instruct patients to limit sun exposure during and for 2 months after treatment with LAZCLUZE in combination with amivantamab. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics.

For Grade

3 reactions, administer oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, reduce the dose or permanently discontinue LAZCLUZE and amivantamab based on severity [see Dosage and Administration (2.4) ] .

5.4 Ocular Toxicity LAZCLUZE, in combination with amivantamab, can cause ocular toxicity, including keratitis. In MARIPOSA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> , ocular toxicity occurred in 16% of patients treated with LAZCLUZE in combination with amivantamab, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose or permanently discontinue amivantamab and continue LAZCLUZE based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .

5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, LAZCLUZE can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, 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. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span>.