Xalkori
Metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test; Metastatic NSCLC whose tumors are ROS1-positive; ALK-positive unresectable, recurrent, or refractory inflammatory myofibroblastic tumors (IMT) in adults and pediatric patients 1 year and older; Relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) in pediatric patients 1 year and older.
NSCLC (adults): 250 mg orally twice daily
Pediatric ALK+ ALCL/IMT: 280 mg/m² orally twice daily (max 500 mg/day)
Take with or without food
Swallow whole; do not crush, dissolve, or open capsules
Capsules: 200 mg, 250 mg
None listed.
- Hepatotoxicity: Fatal drug-induced hepatotoxicity reported (0.1%). Grade 3-4 ALT elevation in 7%. Monitor LFTs every 2 weeks × 2 months, then monthly.
- ILD/Pneumonitis: In 2.9% (Grade 3-4: 1.3%, fatal: 0.5%). D/C if ILD diagnosed.
- QT Prolongation: QTcF >500 ms in 2.1%. Monitor ECGs and electrolytes.
- Bradycardia: In 12%. Avoid with other bradycardic agents.
- Vision Disorders: In 71% (most Grade 1). Visual impairment, photopsia, blurred vision, vitreous floaters.
- Severe GI Toxicity: GI perforation/fistula reported.
Vision disorders (71%), nausea (57%), diarrhea (54%), vomiting (47%), edema (47%), constipation (42%), elevated transaminases (32%), fatigue (27%), decreased appetite (26%), upper respiratory infection (26%), dizziness (22%), neuropathy (20%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR/c-MET), and ROS1 (c-ros). ALK gene rearrangements (most commonly EML4-ALK fusions) drive oncogenic signaling in approximately 5% of NSCLC. Crizotinib binds to the ATP-binding pocket of ALK and inhibits ALK phosphorylation and downstream signal transduction including STAT3, AKT, and ERK1/2 pathways.
Tmax: 4-6 hours. Half-life: 42 hours. Protein binding: 91%. Metabolized by CYP3A4/5. Steady-state by Day 15. Excreted in feces (63%) and urine (22%). Oral bioavailability: 43%.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- PROFILE 1014 — Crizotinib vs. pemetrexed/platinum chemo in 1L ALK+ advanced NSCLC. Phase III, n=343.