Zongertinib is a kinase inhibitor that targets activating mutations in the tyrosine kinase domain of HER2 (ERBB2). It is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy.

Precautions for Zongertinib Administration

Dosage and Administration Method

Dose Adjustment: The recommended dose of zongertinib is determined based on body weight: patients with a body weight < 90kg should take 120mg orally once daily, while those with a body weight ≥ 90kg should take 180mg orally once daily.

Administration Time: Take the drug at a fixed time every day, either with food or on an empty stomach. The tablet must be swallowed whole; do not break, crush, or chew it.

Management of Missed Dose or Vomiting: If a dose is missed and the time elapsed is within 12 hours, the missed dose can be taken. If more than 12 hours have passed, skip the missed dose. If vomiting occurs after taking the drug, do not take an additional dose; administer the next dose as scheduled.

Contraindications and Special Populations

Pregnancy and Lactation: Zongertinib has embryo-fetal toxicity and is contraindicated in pregnant women. Women of childbearing age must use effective contraceptive measures during treatment and for 2 weeks after the last dose. Lactating women should discontinue breastfeeding.

Hepatic or Renal Impairment: Patients with moderate to severe hepatic impairment or moderate to severe renal impairment should use zongertinib with caution; specific dose adjustments must be based on clinical evaluation.

Drug Interactions

Strong CYP3A Inducers: Drugs such as carbamazepine and rifampicin can significantly reduce the plasma concentration of zongertinib, so concurrent use should be avoided. If concurrent use is unavoidable, the dose of zongertinib needs to be increased (e.g., from 120mg to 240mg for patients with a body weight < 90kg).

BCRP Substrate Drugs: Concurrent use with BCRP substrate drugs (e.g., rosuvastatin) may increase the toxicity of the latter. It is necessary to monitor for adverse reactions or adjust the dose accordingly.

Prevention of Adverse Reactions

Diarrhea: The incidence of diarrhea is relatively high (approximately 53%). If Grade 2 or higher diarrhea occurs, treatment should be suspended and anti-diarrheal therapy administered. If diarrhea persists without resolution, permanent discontinuation of treatment is required.

Rash and Nail Disorders: Maintain skin cleanliness and avoid irritation. For nail disorders, regular trimming is necessary to prevent infection.

Monitoring During Zongertinib Administration

Liver Function Monitoring

Monitoring Frequency: Measure ALT, AST, and total bilirubin at baseline and every 2 weeks during the first 12 weeks of treatment, then once a month thereafter. If liver enzyme elevation occurs, increase the monitoring frequency.

Interventions: For Grade 3 ALT/AST elevation or Grade 3 bilirubin elevation: suspend treatment, and resume at a reduced dose after liver function returns to ≤ Grade 1.

Grade 4 Hepatic Impairment or Liver Failure: Permanently discontinue treatment.

Cardiac Function Assessment

Left Ventricular Function: Evaluate left ventricular ejection fraction (LVEF) before treatment, and recheck it regularly during treatment (e.g., every 3 months).

If LVEF decreases to 40%–50% or drops by 10%–19% from baseline: Suspend treatment; if LVEF recovers within 4 weeks, treatment can be resumed at the original dose.

If LVEF < 40% or symptomatic heart failure occurs: Permanently discontinue treatment.

Interstitial Lung Disease (ILD) Monitoring

Symptom Observation: Be alert to ILD/pneumonitis if new or worsening dyspnea, cough, or fever occurs.

Management Principles: For confirmed Grade 2 ILD, suspend treatment and resume at a reduced dose after recovery. For Grade 3 or higher ILD, permanently discontinue treatment.

Other Laboratory Monitoring

Complete Blood Count and Electrolytes: Focus on monitoring lymphopenia (9% of cases are Grade 3–4) and hypokalemia (2.7% of cases are Grade 3–4).

Pancreatic Enzymes: Regularly monitor amylase and lipase to be alert to the risk of pancreatitis.