Ceritinib

Ceritinib is a kinase inhibitor. Targets of Ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, Ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK dependent cancer cells in in vitro and in vivo assays. The recommended dose of Ceritinib is 450 mg orally once daily with food until disease progression or unacceptable toxicity. Common side effects include diarrhea, nausea, vomiting, abdominal pain, elevated liver enzymes, interstitial lung disease, QT prolongation, hyperglycemia, bradycardia, and pancreatitis. It can cause fetal harm during pregnancy, so effective contraception is required.

• ALK-positive metastatic non-small cell lung cancer (NSCLC)

Ceritinib is a kinase inhibitor. Targets of Ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, Ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK dependent cancer cells in in vitro and in vivo assays.

Ceritinib is a kinase inhibitor that inhibits ALK, IGF-1R, InsR, and ROS1. It inhibits ALK autophosphorylation and downstream signaling pathways, thereby preventing the growth of ALK-dependent cancer cells.

Recommended Dose: 450 mg orally once daily with food until disease progression or unacceptable toxicity.

Hepatic Dose: Severe hepatic impairment (Child-Pugh C): Reduce dose by approximately one-third, rounded to the nearest multiple of the 150 mg dosage strength. No dose adjustment is recommended in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

The recommended dose is 450 mg once daily with food. Do not take on an empty stomach.

If a dose of Ceritinib is missed, that dose should be made up unless the next dose is due within 12 hours. If vomiting occurs during treatment, an additional dose should not be administered and the next scheduled dose should be continued.

Common Side Effects (≥10%):

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Elevated liver enzymes (ALT/AST)
• Hyperglycemia
• Bradycardia
• Pancreatitis

Serious Side Effects: Interstitial Lung Disease/Pneumonitis, QT Prolongation, Hepatotoxicity.

• Gastrointestinal Reactions: Monitor and manage diarrhea, nausea, vomiting, or abdominal pain with standard care.
• Hepatotoxicity: Monitor liver function tests (ALT, AST, total bilirubin) once a month and as clinically indicated.
• Interstitial Lung Disease/Pneumonitis: Monitor for pulmonary symptoms.
• QT Prolongation: Avoid in congenital long QT syndrome; monitor with ECGs and electrolytes.
• Hyperglycemia: Monitor fasting serum glucose.
• Bradycardia: Regularly monitor heart rate and blood pressure.
• Pancreatitis: Monitor lipase and amylase.
• Embryo-Fetal Toxicity: Can cause fetal harm; advise effective contraception.

• Hypersensitivity to Ceritinib or any components of this product.

Strong CYP3A Inhibitors: Avoid coadministration with ketoconazole. If unavoidable, reduce Ceritinib dose by approximately one-third. Avoid grapefruit and grapefruit juice.

Strong CYP3A Inducers: Avoid coadministration with rifampin, carbamazepine, phenytoin, St. John's Wort.

CYP3A Substrates: Avoid coadministration with midazolam; if unavoidable, consider dose reduction of CYP3A substrates.

CYP2C9 Substrates: Increase INR monitoring with warfarin; avoid coadministration with CYP2C9 substrates that may cause serious toxicities.

Ceritinib should be taken with food. Grapefruit and grapefruit juice should be avoided as they may inhibit CYP3A.

Ceritinib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment and for 6 months following completion of therapy.

There are no data regarding the presence of Ceritinib or its metabolites in human milk, the effects on the breastfed infant, or its effects on milk production. Breastfeeding is not recommended.

The safety and effectiveness of Ceritinib in pediatric patients have not been established.

Of the 925 patients in clinical studies, 18% were 65 years or older and 5% were 75 years or older. No overall differences in safety or effectiveness were observed between elderly and younger patients.

Hepatic Impairment: Severe hepatic impairment (Child-Pugh C): Reduce dose by approximately one-third, rounded to the nearest multiple of the 150 mg dosage strength. No dose adjustment is recommended in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

Information on renal impairment is not available.

Information on Ceritinib overdosage is not available. In case of overdose, general supportive measures should be instituted.

Store below 30°C in a cool and dry place, away from sunlight. Keep out of reach of children.

Ceritinib