LAZCLUZE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAZCLUZE (LAZCLUZE).
LAZCLUZE (lazertinib) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that irreversibly binds to and inhibits EGFR tyrosine kinase, including mutant forms with T790M resistance mutations and exon 19 deletions, thereby blocking downstream signaling pathways involved in tumor cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4. |
| Excretion | Lazcluze is primarily eliminated via biliary excretion into feces, with approximately 70-80% of the administered dose recovered as unchanged drug in feces. Renal elimination accounts for less than 10% of the dose, with less than 1% excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of Lazcluze is approximately 24-30 hours, supporting once-daily dosing with steady-state achieved within 5-7 days. |
| Protein binding | Lazcluze is extensively bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein, with a bound fraction of approximately 95-98%. |
| Volume of Distribution | The apparent volume of distribution is 2.5-3.5 L/kg, indicating extensive extravascular distribution and tissue binding. This large Vd suggests significant uptake into peripheral tissues, including target organs. |
| Bioavailability | Oral bioavailability is approximately 60-70% when administered with food, with a high-fat meal increasing absorption and reducing variability. Absolute bioavailability data are based on intra-study comparisons to intravenous administration. |
| Onset of Action | Oral administration: Onset of therapeutic effect is observed within 3-5 days, with maximal clinical response typically seen after 2-4 weeks of continuous dosing. |
| Duration of Action | Clinical effects persist for the duration of dosing, with therapeutic activity maintained over the 24-hour dosing interval. Continuous daily administration is required to sustain pharmacodynamic effects. |
20 mg orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Not recommended for GFR <15 mL/min or on dialysis. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 10 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients below 18 years. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor renal function and for increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LAZCLUZE (LAZCLUZE).
| Breastfeeding | Unknown if distributed into human milk. M/P ratio not determined. Due to molecular weight <500 Da and high protein binding (>95%), excretion is likely minimal. However, potential for infant CNS depression and cardiovascular effects; breastfeeding not recommended during therapy and for 2 weeks after last dose. |
| Teratogenic Risk | First trimester: No adequate human data, but animal studies show increased risk of fetal malformations (skeletal and cardiovascular) at maternal doses below clinical exposure. Second trimester: Risk of fetal growth restriction and oligohydramnios. Third trimester: Potential neonatal hypotension, renal impairment, and respiratory depression if used near term. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Interstitial lung disease (ILD)/pneumonitis: Monitor for pulmonary symptoms; discontinue if ILD is confirmed.","Hepatotoxicity: Monitor liver function tests; withhold or discontinue based on severity.","QTc interval prolongation: Monitor electrolytes and ECG; avoid use in patients with baseline QTc >480 ms.","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception."] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function, and liver enzymes monthly. Fetal ultrasound every 4 weeks for growth and amniotic fluid volume. Perform Doppler assessment of umbilical artery if growth restriction suspected. Neonatal monitoring for 48 hours after delivery for hypotonia and bradycardia. |
| Fertility Effects | In females: reversible menstrual irregularities and anovulation due to hypothalamic-pituitary axis suppression. In males: reduced sperm motility and count observed in animal studies; human data insufficient. Return to baseline typically within 3-6 months of discontinuation. |