Cerinib

• Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer (NSCLC):
  Approved for treatment of adults with metastatic ALK-positive NSCLC who have progressed on or are intolerant to crizotinib.
• First-line Therapy:
  Approved as initial therapy for ALK-positive metastatic NSCLC based on efficacy in treatment-naïve patients.
• Off-label Uses:
  Occasionally used in other ALK-rearranged malignancies under clinical trial settings or compassionate use.

• Recommended Dose: 450 mg orally once daily with food.
• Administration:
  Take whole capsules orally with food to enhance absorption.
• Dose Adjustments:
• For severe adverse reactions (e.g., hepatotoxicity, QT prolongation), withhold and resume at reduced dose (e.g., 300 mg daily).
• Adjust dose or discontinue based on toxicity severity.
• Special Populations:
• Hepatic Impairment: Use with caution in moderate impairment; avoid in severe impairment.
• Renal Impairment: No adjustment needed in mild-to-moderate impairment; caution in severe impairment.
• Elderly:
  No specific dose adjustment; monitor for tolerance.

Ceritinib is a potent, selective oral tyrosine kinase inhibitor that targets ALK (anaplastic lymphoma kinase) receptor tyrosine kinase. ALK gene rearrangements produce constitutively active ALK fusion proteins that drive tumor cell proliferation and survival. Ceritinib binds to the ATP-binding site of the ALK kinase domain, inhibiting phosphorylation and downstream signaling pathways involved in tumor growth. It also inhibits ROS1 tyrosine kinase, contributing to its antitumor activity in ALK- and ROS1-rearranged cancers.

• Absorption:
  Oral bioavailability increased when taken with food; peak plasma concentration reached 4 to 6 hours post-dose.
• Distribution:
  Widely distributed; plasma protein binding approximately 97%.
• Metabolism:
  Primarily metabolized by CYP3A4 enzyme in the liver.
• Elimination:
  Excreted mainly via feces (~92%), with minor renal elimination (~1%).
• Half-life:
  Approximately 40 hours, supporting once-daily dosing.

• Pregnancy:
  No adequate human studies; animal studies indicate potential fetal harm. Use only if benefits outweigh risks.
• Lactation:
  Unknown if excreted in human milk; breastfeeding is not recommended during treatment due to potential toxicity.
• Caution:
  Effective contraception advised during and for at least 3 months post-treatment.

• Antineoplastic agent
• ALK tyrosine kinase inhibitor

• Known hypersensitivity to ceritinib or any formulation excipients.

• Hepatotoxicity:
  Monitor liver function tests regularly; may cause severe liver injury.
• Interstitial Lung Disease (ILD)/Pneumonitis:
  Can cause severe, potentially fatal ILD; discontinue immediately if suspected.
• QT Interval Prolongation:
  Monitor ECG; avoid use with other QT-prolonging drugs.
• Hyperglycemia:
  Monitor blood glucose levels; manage accordingly.
• Gastrointestinal Toxicity:
  Diarrhea, nausea, vomiting are common; supportive care may be required.
• Bradycardia:
  Monitor heart rate; caution with other bradycardic agents.

Common (≥20%):

• Diarrhea, nausea, vomiting, abdominal pain.
• Fatigue, increased liver enzymes (ALT, AST).
• Elevated blood glucose.
• Anorexia.

Serious:

• Hepatotoxicity.
• Interstitial lung disease/pneumonitis.
• QT prolongation.
• Bradycardia.
• Pancreatitis (rare).

• CYP3A4 Inhibitors:
  Increase ceritinib plasma levels; may require dose reduction.
• CYP3A4 Inducers:
  Decrease ceritinib levels; avoid concomitant use.
• QT-prolonging Drugs:
  Additive risk of arrhythmia; avoid combination.
• Grapefruit Juice:
  Increases ceritinib levels; avoid consumption.

• Expanded approval for first-line treatment of ALK-positive metastatic NSCLC.
• Emphasis on dose administration with food to improve tolerability and bioavailability.
• Updated warnings regarding hepatotoxicity and ILD risk.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep capsules in original container until use.
• Do not freeze.
• Keep out of reach of children.