Ceritinib is used for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as confirmed by an FDA-approved test.

Ceritinib is a kinase inhibitor. It inhibits multiple targets identified in biochemical and cellular studies, including ALK, insulin-like growth factor-1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, Ceritinib shows the highest activity against ALK. It blocks ALK autophosphorylation and inhibits downstream signaling proteins such as STAT3, thereby suppressing the growth and proliferation of ALK-dependent cancer cells in both in vitro and in vivo conditions.

Absorption: After oral administration, peak plasma concentration (Cmax) is reached within approximately 4 to 6 hours. Both AUC and Cmax increase proportionally with doses ranging from 50 to 750 mg under fasting conditions. The absolute bioavailability of Ceritinib has not been established.

Distribution: Ceritinib is approximately 97% bound to plasma proteins, regardless of concentration. The apparent volume of distribution is about 4230 L after a single 750 mg dose under fasting conditions. It shows slight preferential distribution into red blood cells compared to plasma, with a blood-to-plasma ratio of approximately 1.35.

Elimination: Following a single 750 mg fasting dose, the mean terminal half-life is about 41 hours. Ceritinib exhibits nonlinear pharmacokinetics over time. The apparent clearance is lower at steady state (33.2 L/h) compared to after a single dose (88.5 L/h).

Metabolism: In vitro studies indicate that CYP3A is the primary enzyme responsible for the metabolism of Ceritinib. After administration of a radiolabeled dose, the parent compound remains the major circulating component (approximately 82%) in plasma.

Excretion: After oral administration of a radiolabeled 750 mg dose under fasting conditions, about 92.3% of the dose is recovered in feces (with approximately 68% as unchanged drug), and about 1.3% is recovered in urine.

Patients should be selected for treatment of metastatic NSCLC with Ceritinib based on the presence of ALK positivity in tumor specimens. The recommended dose of Ceritinib is 450 mg orally once daily with food until disease progression or unacceptable toxicity. 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 the course of treatment, an additional dose should not be administered and the next scheduled dose of Ceritinib should be continued. Or, as directed by the registered physician.

Effect of Other Drugs on Ceritinib: Strong CYP3A inhibitors can increase Ceritinib exposure and should generally be avoided. If co-administration with strong CYP3A inhibitors (such as certain antivirals, macrolide antibiotics, or antifungals) is necessary, the Ceritinib dose should be reduced appropriately. After discontinuation of the inhibitor, the previous Ceritinib dose may be resumed. Grapefruit and grapefruit juice should be avoided during treatment.

Strong CYP3A Inducers: Strong CYP3A inducers (e.g., Rifampin) may reduce Ceritinib exposure. Concomitant use with agents such as Carbamazepine, Phenytoin, Rifampin, and St. John’s Wort should be avoided.

Effect of Ceritinib on Other Drugs (CYP3A Substrates): Ceritinib may increase the exposure of CYP3A substrates (e.g., Midazolam). If unavoidable, dose adjustment of the affected drug may be required.

CYP2C9 Substrates: Ceritinib may increase the exposure of CYP2C9 substrates such as Warfarin. Monitoring (e.g., INR) should be increased if co-administration is necessary, and dose adjustment may be required.

Ceritinib is contraindicated in patients with known hypersensitivity to Ceritinib or any of its components.

• Gastrointestinal adverse reactions
• Hepatotoxicity
• Interstitial lung disease/Pneumonitis
• QT interval prolongation
• Hyperglycemia
• Bradycardia
• Pancreatitis

Ceritinib may cause fetal harm if administered during pregnancy. Women should be informed of the potential risk to the fetus. There are no adequate data on its presence in human milk or its effects on the breastfed infant. Due to the risk of serious adverse reactions, including gastrointestinal toxicity, hepatotoxicity, pneumonitis, bradycardia, and pancreatitis, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.

Gastrointestinal Adverse Reactions: Severe gastrointestinal toxicity has been observed in patients receiving Ceritinib, particularly at higher doses under fasting conditions. Common symptoms include diarrhea, nausea, vomiting, and abdominal pain, with some cases being severe. These reactions may require dose interruption, reduction, or discontinuation. Patients should be closely monitored and managed with supportive measures such as antiemetics, antidiarrheals, and fluid replacement. Depending on severity, treatment may be resumed at a lower dose.

Hepatotoxicity: Liver toxicity has been reported with Ceritinib use. Significant increases in ALT and AST levels, including severe elevations, have occurred. Liver function tests should be performed regularly, especially during the initial months of therapy. If abnormalities occur, dose modification or discontinuation may be necessary.

Interstitial Lung Disease (ILD)/Pneumonitis: Serious, life-threatening, or fatal ILD/pneumonitis has been reported. Patients should be monitored for respiratory symptoms such as cough and dyspnea. If suspected, Ceritinib should be discontinued.

QT Interval Prolongation: QT interval prolongation has been reported and may increase the risk of ventricular arrhythmias, including Torsades de Pointes or sudden death. ECG and electrolyte monitoring should be conducted periodically, especially in patients with cardiac conditions or those on QT-prolonging drugs.

Hyperglycemia: Elevated blood glucose levels have been reported during treatment. Blood glucose should be checked before and during therapy. If not adequately controlled, temporary discontinuation and dose adjustment may be required.

Bradycardia: Slowing of heart rate has been observed. Heart rate and blood pressure should be monitored regularly. Caution is required when used with other medications that lower heart rate.

Pancreatitis: Cases of pancreatitis have been reported. Serum lipase and amylase levels should be monitored before and during treatment. Based on severity, Ceritinib may need to be withheld or resumed at a reduced dose.

Embryo-Fetal Toxicity: Ceritinib may cause harm to the fetus. Women of reproductive potential should use effective contraception during treatment and for 6 months after therapy. Men with female partners of reproductive potential should use contraception for 3 months after treatment.

Females: Women of reproductive potential should use effective contraception during treatment and for 6 months after completion of therapy.

Males: Male patients with female partners of reproductive potential should use condoms during treatment and for 3 months after therapy completion.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No significant differences in safety or effectiveness have been observed between elderly and younger patients.

Hepatic Impairment: In patients with severe hepatic impairment (Child-Pugh C), dose reduction is recommended. No adjustment is required in mild to moderate impairment.

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