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 echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met.
The most common adverse reactions (≥25%) are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.
Based on its mechanism of action, Crizotinib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of Crizotinib during pregnancy. Females of reproductive potential should be advised of the potential risk to a fetus and use of effective contraception.
There is no information regarding the presence of Crizotinib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for adverse reactions in breastfed infants patients should not breastfeed during treatment with Crizotinib and for 45 days after the final dose.
Hepatotoxicity: Patients should undergo periodic liver testing. Crizotinib should be temporarily suspended, dose reduced or permanently suspended
Interstitial lung disease (ILD)/ Pneumonitis: Drug should be permanently discontinued in patients with ILD/ Pneumonitis
QT interval prolongation: Electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong QT should be monitored. Crizotinib should be temporarily suspended, dose reduced or permanently suspended
Bradycardia: Crizotinib can cause bradycardia. Heart rate and blood pressure should be regularly monitored. Crizotinib should be temporarily suspended, dose reduced or permanently suspended
Severe visual loss: Ophthalmological evaluation should be performed. Crizotinib should be discontinued in severe visual loss
Embryo-fetal toxicity: Crizotinib can cause fetal harm. Females of reproductive potential should be advised of the potential risk to a fetus and use of effective contraception
Targeted Cancer Therapy
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
