Precautions when using ceritinib/ceritinib

In the clinical study of Ceritinib in the treatment of non-small cell lung cancer (NSCLC), warnings and precautions such as gastrointestinal adverse reactions, liver toxicity, interstitial lung disease/pneumonitis, QT interval prolongation, hyperglycemia, etc. occurred. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Gastrointestinal adverse reactions: Common adverse reactions include diarrhea, nausea, vomiting or abdominal pain. Monitor and manage patients using standard care, including antidiarrheal medications, antiemetics, or fluid replacement, as indicated. Discontinue ceritinib if gastrointestinal adverse effects are severe or intolerable and do not respond to antiemetics or antidiarrheals. After improvement, ceritinib was resumed at a reduced dose.

2. Hepatotoxicity: In clinical studies, patients experienced an increase in alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN), an increase in aspartate aminotransferase (AST) > 5 times ULN, an increase in total bilirubin > 2 times ULN, and an increase in alkaline phosphatase < 2 times ULN. Liver laboratory tests, including ALT, AST, and total bilirubin, were performed monthly as clinically indicated, with more frequent testing in patients with elevated transaminases.

3. Interstitial lung disease/pneumonitis: Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes of ILD/pneumonitis and permanently discontinue ceritinib in patients diagnosed with treatment-related ILD/pneumonitis.

4. QT interval prolongation: may lead to increased risk of ventricular tachyarrhythmia (such as torsade de pointes) or sudden death. If possible, ceritinib should be avoided in patients with congenital long QT syndrome. Perform periodic ECG and electrolyte monitoring in patients who have congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or are taking drugs known to prolong the QTc interval.

5. Hyperglycemia: Monitor fasting blood glucose before starting ceritinib treatment, and then monitor regularly as clinically indicated. Initiate or optimize antihyperglycemic medications as indicated.

6. Bradycardia: defined as heart rate <50 beats per minute). If possible, avoid coadministration of ceritinib with other products known to cause bradycardia (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, and digoxin). Monitor heart rate and blood pressure regularly.

7. Pancreatitis: Pancreatitis occurs in patients treated with ceritinib. Monitor lipase and amylase before initiating treatment with ceritinib and periodically thereafter as clinically indicated.

8. Embryo-Fetal toxicity: Based on its mechanism of action and animal study results, ceritinib can cause harm to the fetus when used in pregnant women. In animal studies, administration of celitinib to rats and rabbits during organogenesis resulted in increased skeletal abnormalities in rats and rabbits at maternal plasma exposures below the recommended human dose.

Inform pregnant women of potential risks to the fetus. It is recommended that women of childbearing potential use effective contraception during treatment with ZYKADIA and for 6 months after the end of treatment. Based on the potential for genotoxicity, it is recommended that men with female partners of reproductive potential use condoms during treatment with ceritinib and for 3 months after completion of treatment.

Reference materials:https://go.drugbank.com/drugs/DB09063