Version July 2025
Dosage guidance:
Safety: Administer anticoagulant prophylaxis to prevent venous thromboembolic events (VTE) for the first 4 months of treatment with lazertinib; use of vitamin K antagonists is not recommended. Consider discontinuation of anticoagulant prophylaxis if there are no signs or symptoms of VTE during the first 4 months of treatment. Administer alcohol-free (eg, isopropanol-free, ethanol-free) emollient cream and consider prophylactic measures (eg, oral antibiotics) to reduce the risk of dermatologic reactions. Advise patients to wear protective clothing, use broad spectrum UVA/UVB sunscreen, and limit sun exposure during and for 2 months after treatment.
Clinical considerations: Select patients for the first-line treatment of non–small cell lung cancer based on the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens (if these mutations are not detected in plasma specimen, test tumor tissue).
Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation: Oral: 240 mg once daily (in combination with amivantamab); continue until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed, administer the missed dose if ≤12 hours from scheduled administration time. If a dose is missed by >12 hours from the scheduled administration time, skip the missed dose and administer the next dose at the scheduled time. If a dose is vomited, do not administer a replacement dose (administer the next dose at the scheduled time).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function prior to treatment initiation:
eGFR 30 to 89 mL/minute: No dosage adjustment is necessary.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Altered hepatic function prior to treatment initiation:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin ≤1.5 times ULN and any AST) or moderate (total bilirubin ≤1.5 to 3 times ULN and any AST) impairment: No dosage adjustment is necessary.
Severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
|
Dosage reduction level |
Recommended lazertinib dosage and schedule |
|---|---|
|
Usual (initial) dose |
240 mg once daily |
|
First dose reduction level |
160 mg once daily |
|
Second dose reduction level |
80 mg once daily |
|
Discontinue lazertinib if unable to tolerate therapy after 2 dose reductions. | |
|
Adverse reaction |
Severity |
Lazertinib dosage modification |
|---|---|---|
|
a ILD = interstitial lung disease; VTE = venous thromboembolic events. | ||
|
Dermatologic toxicity (including dermatitis acneiform, pruritus, dry skin) |
General recommendations |
If skin reactions develop, administer topical corticosteroids and topical and/or oral antibiotics. Promptly refer patients with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. |
|
Grade 1 |
Initiate supportive care management. | |
|
Grade 2 |
Initiate supportive care management. No improvement after 2 weeks: Continue lazertinib at the same dose (and reduce amivantamab dose). Reassess every 2 weeks. If no improvement, reduce lazertinib dose until ≤ grade 1; may resume at previous lazertinib dose at the discretion of the health care provider. | |
|
Grade 3 |
Initiate supportive care management. Administer oral corticosteroids and consider dermatologic consultation. Withhold lazertinib (and amivantamab) until recovery to ≤ grade 2; resume lazertinib at the same dose or consider dose reduction (and resume amivantamab at a reduced dose). No improvement within 2 weeks: Permanently discontinue lazertinib (and amivantamab). | |
|
Grade 4 (including severe bullous, blistering, or exfoliative skin conditions) |
Initiate supportive care management. Withhold lazertinib until recovery to ≤ grade 2 or baseline (and permanently discontinue amivantamab); resume lazertinib at a reduced dose at the discretion of the health care provider. | |
|
Ocular toxicity |
New or worsening eye symptoms (including keratitis) |
Promptly refer to an ophthalmologist. Continue lazertinib based on the severity (and withhold, reduce the dose, or permanently discontinue amivantamab based on severity). |
|
Pulmonary toxicity (ILD/pneumonitis) |
Any grade |
Suspected ILD/pneumonitis: Immediately withhold lazertinib (and amivantamab). Confirmed ILD/pneumonitis: Permanently discontinue lazertinib (and amivantamab). |
|
VTE |
Grade 2 or 3 |
Withhold lazertinib (and amivantamab) and administer anticoagulant treatment as clinically indicated. Resume lazertinib (and amivantamab) at the same dose level at the discretion of the health care provider once anticoagulation treatment has been initiated. |
|
Grade 4 or recurrent grade 2 or 3 despite therapeutic anticoagulation |
Withhold lazertinib (permanently discontinue amivantamab), and administer anticoagulant treatment as clinically indicated. Resume lazertinib at the same dose level at the discretion of the health care provider once anticoagulation treatment has been initiated. | |
|
Other adverse reactions |
Grade 3 or 4 |
Withhold lazertinib (and amivantamab) until recovery to ≤ grade 1 or baseline; resume both lazertinib and amivantamab at reduced doses or resume lazertinib alone. Consider permanently discontinuing lazertinib (and amivantamab) if recovery does not occur within 4 weeks. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults in combination with amivantamab.
>10%:
Cardiovascular: Edema (43%), venous thromboembolism (36%)
Dermatologic: Nail disease (nail toxicity: 71%), pruritus (24%), skin rash (86%), xeroderma (25%)
Endocrine & metabolic: Decreased serum albumin (89%), decreased serum calcium (41%), decreased serum magnesium (25%), decreased serum potassium (30%), decreased serum sodium (38%), hypermagnesemia (12%)
Gastrointestinal: Abdominal pain (11%), constipation (29%), decreased appetite (24%), diarrhea (31%; grades 3/4: 3%), nausea (21%; grades 3/4: 1%), stomatitis (43%; grades 3/4: 2%), vomiting (12%; grades 3/4: <1%)
Hematologic & oncologic: Decreased hemoglobin (47%; grades 3/4: 4%), decreased neutrophils (15%; grades 3/4: 1%), decreased platelet count (52%; grades 3/4: <1%), decreased white blood cell count (38%; grades 3/4: 1%), hemorrhage (25%; grades 3/4: 1%)
Hepatic: Increased gamma-glutamyl transferase (39%), increased serum alanine aminotransferase (65%), increased serum alkaline phosphatase (45%), increased serum aspartate aminotransferase (52%)
Nervous system: Dizziness (14%), fatigue (32%), headache (13%), paresthesia (35%)
Neuromuscular & skeletal: Musculoskeletal pain (47%)
Ophthalmic: Conjunctivitis (11%), ocular toxicity (16%)
Renal: Increased serum creatinine (26%)
Respiratory: Cough (19%), dyspnea (14%)
Miscellaneous: Fever (12%)
1% to 10%:
Gastrointestinal: Hemorrhoids (10%)
Nervous system: Insomnia (10%)
Respiratory: Interstitial lung disease (≤3%), pleural effusion (2%), pneumonia (4%), pneumonitis (≤3%)
Frequency not defined: Respiratory: Respiratory failure
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Dermatologic toxicity: Lazertinib (in combination with amivantamab) has been associated with severe rash, including dermatitis acneiform, pruritus, and dry skin. Rash occurred in a majority of patients treated with the combination of lazertinib and amivantamab, including grade 3 events in one-fourth of patients. The median time to onset of rash was 14 days (range: 1 to 556 days).
• Ocular toxicity: Ocular toxicity, including keratitis, has been observed in patients treated with lazertinib (in combination with amivantamab); grade 3 or 4 events occurred in a small number of patients.
• Pulmonary toxicity: Interstitial lung disease/pneumonitis has occurred in patients treated with lazertinib (in combination with amivantamab), including a fatal case.
• Venous thromboembolism: Lazertinib (in combination with amivantamab) can cause serious and fatal venous thromboembolic events (VTE), including deep vein thrombosis and pulmonary embolism. In a clinical trial, one-third of patients receiving lazertinib (in combination with amivantamab) developed a VTE (including some grade 3 and higher events); VTE developed while receiving anticoagulation in a small number of patients. The majority of VTEs occurred within with first 4 months of therapy; median time to onset of VTE was 84 days (range: 6 to 777 days).
Other warnings/precautions:
• Appropriate use: Confirm the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens (if mutations are not detected in plasma specimen, test tumor tissue) for first-line treatment of locally advanced or metastatic non–small cell lung cancer. Information on diagnostic tests approved for detection of EGFR mutations may be found at https://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as mesylate [strength expressed as base]:
Lazcluze: 80 mg, 240 mg
No
Tablets (Lazcluze Oral)
80 mg (per each): $363.96
240 mg (per each): $727.92
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Oral: May be administered with or without food. Swallow whole; do not crush, split, or chew. When administered with amivantamab on the same day, administer lazertinib any time prior to amivantamab. Administer anticoagulant prophylaxis to prevent venous thromboembolic events for the first 4 months of lazertinib/amivantamab treatment (do not use a vitamin K antagonist).
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Lazertinib may cause reproductive toxicity and has a structural and/or toxicity profile similar to existing hazardous drugs.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (Ref).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (Ref). Refer to institution-specific handling policies/procedures.
Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation: First-line treatment (in combination with amivantamab) of locally advanced or metastatic non–small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations (as detected by an approved test) in adults.
Lazertinib may be confused with afatinib, alectinib, crizotinib, dacomitinib, erlotinib, gefitinib, lapatinib, larotrectinib, lenvatinib, lorlatinib, osimertinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Lazertinib may increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Cladribine: BCRP/ABCG2 Inhibitors may increase serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Lazertinib. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Lazertinib. Risk X: Avoid
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
PAZOPanib: BCRP/ABCG2 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Rosuvastatin: BCRP/ABCG2 Inhibitors may increase serum concentration of Rosuvastatin. Risk C: Monitor
Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 3 weeks after the last dose of lazertinib. Patients with partners who could become pregnant should also use effective contraception during therapy and for 3 weeks after the last lazertinib dose.
Adverse effects to fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to lazertinib may cause fetal harm. Advise patients of the potential risk to a fetus.
It is not known if lazertinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 3 weeks after the last dose of lazertinib.
Assess for epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens (if mutations are not detected in plasma specimen, test tumor tissue). Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Monitor for signs and symptoms of venous thromboembolic events (VTE). Monitor for new or worsening symptoms indicative of interstitial lung disease or pneumonitis (eg, dyspnea, cough, fever). Monitor for dermatologic reactions (eg, dermatitis acneiform, pruritus, dry skin. Monitor for signs or symptoms of ocular toxicity (eg, new or worsening eye symptoms). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Lazertinib is a highly selective, third-generation kinase inhibitor of epidermal growth factor receptor (EGFR) that inhibits EGFR exon 19 deletions and exon 21 L858R substitution mutations, resulting in antitumor activity in susceptible non–small cell lung cancers (NSCLC) (Ref). In NSCLC studies (with EGFR L858R mutation), lazertinib demonstrated increased in vivo antitumor activity in combination with amivantamab (an EGFR-MET bispecific antibody) when compared with animal models of either agent alone.
Distribution: Vd: 2,680 L.
Protein binding: ~99.2%.
Metabolism: Primarily by glutathione conjugation, either enzymatic via glutathione-S-transferase (GST) or nonenzymatic, as well as by CYP3A4.
Half-life elimination: 3.7 days.
Time to peak: 2 to 4 hours.
Excretion: Feces: ~86% (<5% as unchanged drug); urine: 4% (<0.2% as unchanged drug).
Clearance: 36.4 L/hour.
