Ceritinib (Zykadia) is a kinase inhibitor indicated for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), as detected by a U.S. FDA-approved test.

What are the Precautions for Ceritinib (Zykadia) Administration?

Pre-Treatment Evaluation

Patient Selection Criteria: Tumors must be confirmed as ALK-positive using an FDA-approved detection method.

Comorbid Condition Assessment: A detailed evaluation of the patient’s comorbidities is required, with particular caution in cases of congestive heart failure, bradycardia, electrolyte abnormalities, or concurrent use of medications known to prolong the QTc interval.

Organ Function Assessment: Hepatic function, renal function, pancreatic function, and blood glucose levels must be evaluated prior to treatment to establish baseline data for subsequent comparative monitoring.

Reproductive Status Assessment: For females of reproductive potential, pregnancy status should be confirmed, and guidance on effective contraceptive measures provided.

Gastrointestinal Adverse Reactions

Ceritinib may cause severe gastrointestinal adverse reactions, including diarrhea, nausea, vomiting, or abdominal pain.

These symptoms occurred in 79% of patients receiving the recommended dose of 450 mg taken with food.

If severe or intolerable gastrointestinal reactions occur and are unresponsive to antiemetic or antidiarrheal medications, discontinue ceritinib temporarily. Resume treatment at a lower dose after symptom improvement.

Risk of Hepatotoxicity

Ceritinib may induce drug-induced liver injury. Elevations in alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN) occurred in 28% of patients, and elevations in aspartate aminotransferase (AST) > 5 times ULN in 16% of patients.

Monthly monitoring of hepatic function is required. The frequency of testing should be increased if transaminase elevations occur.

Interstitial Lung Disease (ILD)/Pneumonitis

The incidence of ILD/pneumonitis in patients treated with ceritinib is 2.4%.

Upon diagnosis of treatment-related ILD/pneumonitis, permanent discontinuation of ceritinib is required.

QT Interval Prolongation

Ceritinib may prolong the QTc interval, increasing the risk of ventricular tachycardia or sudden cardiac death.

Regular monitoring of electrocardiograms (ECGs) and electrolytes is recommended, especially in patients with heart failure, bradycardia, electrolyte abnormalities, or concurrent use of medications known to prolong the QTc interval.

Drug Interactions

CYP3A Inhibitors and Inducers: Avoid concurrent use with strong CYP3A inhibitors or inducers. If concurrent use of a strong CYP3A inhibitor is unavoidable, reduce the ceritinib dose.

CYP3A Substrates: Avoid concurrent use with sensitive CYP3A substrates.

CYP2C9 Substrates: Avoid concurrent use with CYP2C9 substrates for which minimal concentration changes may lead to severe toxicity.

QT Interval-Prolonging Medications: Ceritinib causes concentration-dependent QTc interval prolongation. Whenever possible, avoid concurrent use with other products known to have the potential to prolong the QTc interval.

Bradycardia-Inducing Medications: Ceritinib may cause bradycardia. Whenever possible, avoid concurrent use with other products known to cause bradycardia.

Monitoring During Ceritinib (Zykadia) Administration

Hepatic Function Monitoring

Conduct laboratory tests for hepatic function (including ALT, AST, and total bilirubin) at least monthly.

For patients with transaminase elevations, increase the frequency of monitoring.

Electrocardiogram (ECG) Monitoring

Regular ECG monitoring is recommended for patients with cardiac disease, electrolyte abnormalities, or concurrent use of medications known to prolong the QTc interval.

Blood Glucose Monitoring

Monitor fasting blood glucose prior to treatment, followed by regular monitoring based on clinical indications.