Crizocent 250

• ALK-positive metastatic non-small cell lung cancer (NSCLC)
• ROS1-positive metastatic non-small cell lung cancer (NSCLC)

Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed ALK fusion proteins or c-Met.

Recommended Dose (Oral): 250 mg twice daily.

Dose Modifications: Dosing interruption and/or dose reduction to 200 mg twice daily may be required; decrease to 250 mg once daily if further reduction is needed.

Renal Dose: Severe renal impairment (CrCl <30 mL/min): 250 mg once daily. Mild (CrCl 60-89) or moderate (CrCl 30-59) renal impairment: No starting dose adjustment needed.

Hepatic Dose: Caution advised in hepatic impairment.

Common Side Effects (≥25%):

• Vision disorders
• Nausea
• Diarrhea
• Vomiting
• Edema
• Constipation
• Elevated transaminases
• Fatigue
• Decreased appetite
• Upper respiratory infection
• Dizziness
• Neuropathy

Serious Side Effects: Hepatotoxicity, ILD/Pneumonitis, QT prolongation, Bradycardia, Severe visual loss, Embryo-fetal toxicity.

[CONSULT YOUR DOCTOR] Crizotinib is unsafe to use during pregnancy as there is definite evidence of risk to the developing baby. Pregnancy Category D.

• [UNSAFE] Crizotinib may decrease alertness, affect your vision or make you feel sleepy and dizzy. Do not drive if these symptoms occur.
• Hepatotoxicity: Periodic liver testing required.
• ILD/Pneumonitis: Permanently discontinue in patients with ILD/Pneumonitis.
• QT prolongation: Monitor ECGs and electrolytes.
• Bradycardia: Regularly monitor heart rate and blood pressure.
• Severe visual loss: Perform ophthalmological evaluation; discontinue in severe visual loss.
• Contraindicated during pregnancy; effective contraception required.

Information on Crizotinib overdosage is not available. In case of overdose, symptomatic and supportive treatment should be given.

Keep below 30°C temperature, away from light & moisture. Keep out of reach of children.