Ceritinib (Zykadia) is a kinase inhibitor indicated for the treatment of metastatic non-small cell lung cancer (NSCLC), specifically in adult patients whose tumors are confirmed as ALK-positive by an FDA-approved test. As a highly effective targeted therapy, ceritinib exerts therapeutic effects while also inducing a range of side effects, including several serious adverse reactions that require close monitoring.

Side Effects of Ceritinib (Zykadia)

Gastrointestinal Adverse Reactions

The most common side effects of ceritinib primarily affect the gastrointestinal system.

Specific manifestations: Diarrhea occurs in 59% of patients.

Nausea occurs in 43% of patients.

Vomiting occurs in 38% of patients.

Among these, only 0.9% of patients experience grade 3 diarrhea, 0.9% develop grade 3 vomiting, and 0.9% require dose adjustments due to these symptoms.

Systemic Reactions

Fatigue is a common systemic adverse reaction during ceritinib treatment, occurring in approximately 45% of patients in the 450 mg with food dosage group, with 7% being severe.

Metabolic and Nutritional Issues

Other common side effects observed in clinical studies include: decreased appetite (34%), weight loss (24%), etc.

Severe Side Effects of Ceritinib (Zykadia)

Risk of Hepatotoxicity

Ceritinib can cause drug-induced liver injury, which requires special attention.

28% of patients experience alanine aminotransferase (ALT) elevations > 5 times the upper limit of normal (ULN).

16% of patients experience aspartate aminotransferase (AST) elevations > 5 times ULN.

0.3% of patients experience ALT > 3 times ULN accompanied by total bilirubin > 2 times ULN.

Approximately 1% of patients require permanent discontinuation of ceritinib due to hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

The incidence rate is 2.4%.

1.3% of cases are of grade 3 or 4 severity.

Fatal events occurred in 0.2% of patients.

QT Interval Prolongation

Ceritinib can prolong the QTc interval, increasing the risk of ventricular tachycardia.

1.3% of patients develop a QTc interval > 500 milliseconds.

0.2% of patients discontinued treatment due to this adverse reaction.

Precautions for Ceritinib (Zykadia) Administration

Regular Monitoring Requirements

Hepatic Function Monitoring: Measure ALT, AST, and total bilirubin at least once monthly.

Cardiac Monitoring: For patients with congestive heart failure or bradyarrhythmia, regularly monitor electrocardiograms (ECGs) and electrolytes.

Metabolic Monitoring: Monitor fasting blood glucose before treatment and periodically during treatment.

Pancreatic Monitoring: Measure lipase and amylase before treatment and as clinically indicated.

Use in Special Populations

Patients with Hepatic Impairment: For patients with severe hepatic impairment, reduce the dose by approximately one-third.

Pregnant Women: Ceritinib may cause fetal harm; inform patients of the potential risks.

Lactating Women: Breastfeeding is not recommended during treatment and for 2 weeks after the completion of therapy.

Drug Interactions

CYP3A Inhibitors: Avoid concurrent use with strong CYP3A inhibitors.

CYP3A Inducers: Avoid concurrent use with strong CYP3A inducers.

QT Interval-Prolonging Medications: Whenever possible, avoid concurrent use with medications known to prolong the QT interval.