lazertinib

Absorption: Unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 99%.

Metabolism/Excretion: Primarily metabolized by glutathione conjugation as well as by the CYP3A4 isoenzyme. 86% excreted in feces (<5% as unchanged drug) and 4% excreted in urine.

Half-Life: 3.7 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment or end-stage renal disease;
Severe hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: deep vein thrombosis (DVT), edema

Derm: dry skin, nail toxicity, pruritus, rash, dermatitis acneiform

EENT: conjunctivitis, keratitis

F and E: hypermagnesemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia

GI: ↓appetite, ↑liver enzymes, abdominal pain, constipation, diarrhea, hemorrhoids, hypoalbuminemia, nausea, stomatitis, vomiting

GU: ↑serum creatinine, ↓fertility

Hemat: anemia, hemorrhage, leukopenia, neutropenia, thrombocytopenia

MS: pain

Neuro: dizziness, fatigue, headache, insomnia, paresthesia

Resp: cough, dyspnea, pulmonary embolism (PE), INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of CYP3A4 substrates, including midazolam.
May ↑ levels and risk of toxicity of breast cancer resistance protein substrates, including rosuvastatin.

Route/Dosage ⬆ ⬇

PO (Adults ): 240 mg once daily; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 80 mg; 240 mg

Assessment ⬆ ⬇

Assess for signs/symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema). If Grade 2 or 3 thromboembolic event occurs, hold lazertinib and amivantamab; administer anticoagulant treatment as clinically indicated, then resume lazertinib and amivantamab at same dose. If Grade 4 or recurrent Grade 2 or 3 thromboembolic events occurs despite therapeutic level anticoagulation, hold lazertinib and permanently discontinue amivantamab; administer anticoagulant treatment as clinically indicated, then treatment can continue with lazertinib at same dose.
Monitor for signs/symptoms of ILD or pneumonitis such as dyspnea, cough, hypoxia, fever. CT scan or chest x-ray can confirm. If ILD or pneumonitis suspected, hold lazertinib. If ILD or pneumonitis confirmed,permanently discontinue lazertinib.
Monitor for dermatologic reactions including dermatitis, pruritus, dry skin, and acneiform during therapy; may occur ≥ 2 mo after therapy is complete. Treat as indicated with topical corticosteroids and topical and/or oral antibiotics.If Grade 2 dermatologic reaction occurs, if no improvement after 2 wk, ↓ amivantamab dose and continue lazertinib at same dose; reassess every 2 wk. If no improvement, ↓ lazertinib dose until reaction is Grade ≤1. If Grade 3 dermatologic reaction occurs, administer oral corticosteroids and hold lazertinib and amivantamab until recovery to Grade ≤2. Resume lazertinib at same or ↓ dose, resume amivantamab at ↓ dose. Permanently discontinue lazertinib and amivantamab if no improvement within 2 wk. If Grade 4 dermatologic reaction occurs, permanently discontinue amivantamab and hold lazertinib until recovery to Grade ≤2. Resume lazertinib at ↓ dose.
Monitor for ocular toxicity such as keratitis or conjunctivitis during therapy. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. If ocular toxicity confirmed,↓ lazertinib dose, or permanently discontinue amivantamab and continue lazertinib based on severity.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy.
Screen for the presence of EGFR exon 19 deletions and exon 21 L858R substitution mutations in tumor specimens with an FDA-approved companion diagnostic test.

Implementation ⬆ ⬇

Administer anticoagulant prophylaxis to prevent venous thromboembolic events for the 1st 4 mo of treatment when initiating lazertinib in combination with amivantamab. Vitamin K antagonist not recommended.
PO: Administer lazertinib with or without food any time prior to amivantamab when given on the same day. DNC: Swallow tablets whole; do not crush, split, or chew.
Dose Reductions for Adverse Reactions: 1st Dose ↓: 160 mg once daily; 2nd Dose ↓: 80 mg once daily; 3rd Dose ↓: Discontinue lazertinib.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of lazertinib. Advise patient to take as directed. If dose missed <12 hr of scheduled time, instruct patient to take the missed dose. If >12 hr since the dose was to be given, instruct the patient to take the next dose at its scheduled time. If vomiting occurs any time after taking dose, instruct patient to take the next dose at its next regularly scheduled time. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Emphasize need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests and eye exams may be needed.
Advise patient to notify health care professional and promptly seek treatment for signs/symptoms of DVT or PE such as chest pain, trouble breathing, fast heart beat, calf pain or tenderness, lower leg swelling.
Instruct patient to notify health care professional promptly of any new rash, nail changes, or eye symptoms.
Inform patient to immediately report signs/symptoms of ILD or pneumonitis such as cough, trouble breathing, or fever.
Advise patient to apply alcohol free emollient cream to dry skin.
Encourage patients to limit sun exposure during and for 2 mo after treatment, to wear protective clothing, and use broad-spectrum UVA/UVB sunscreen to ↓ risk of dermatologic adverse reactions.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise women of reproductive potential to use effective contraception and not to breastfeed during treatment and for 3 wk after final dose. Advise men with female partners of reproductive potential to use effective contraception during treatment and for 3 wk after final dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇