Drug Detail:Xalkori (Crizotinib [ kriz-oh-ti-nib ])
Generic Name: CRIZOTINIB 250mg
Dosage Form: capsule
Drug Class: Multikinase inhibitors
Patient Selection
Select patients for the treatment of metastatic NSCLC with XALKORI based on the presence of ALK or ROS1 positivity in tumor specimens [see Indications and Usage (1) and Clinical Studies (14.1, 14.2)].
Information on FDA-approved tests for the detection of ALK and ROS1 rearrangements in NSCLC is available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm.
Recommended Dosing
The recommended dose of XALKORI is 250 mg orally twice daily until disease progression or no longer tolerated by the patient.
The recommended dose of XALKORI in patients with pre-existing moderate hepatic impairment [any aspartate aminotransferase (AST) and total bilirubin >1.5 times the upper limit of normal (ULN) and ≤3 times ULN] is 200 mg orally twice daily. The recommended dose of XALKORI in patients with pre-existing severe hepatic impairment [any AST and total bilirubin >3 times ULN] is 250 mg orally once daily [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
The recommended dose of XALKORI in patients with severe renal impairment [creatinine clearance (CLcr) <30 mL/min] not requiring dialysis is 250 mg orally once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
XALKORI may be taken with or without food. Swallow capsules whole. If a dose of XALKORI is missed, make up that dose unless the next dose is due within 6 hours. If vomiting occurs after taking a dose of XALKORI, take the next dose at the regular time.
Dose Modification
Reduce dose as below, if 1 or more dose reductions are necessary due to adverse reactions of Grade 3 or 4 severity, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0:
- First dose reduction: XALKORI 200 mg taken orally twice daily
- Second dose reduction: XALKORI 250 mg taken orally once daily
- Permanently discontinue if unable to tolerate XALKORI 250 mg taken orally once daily
Dose reduction guidelines are provided in Tables 1 and 2.
| Grade | XALKORI Dosing |
|---|---|
|
|
| Grade 3 | Withhold until recovery to Grade 2 or less, then resume at the same dose schedule |
| Grade 4 | Withhold until recovery to Grade 2 or less, then resume at next lower dose |
| Criteria | XALKORI Dosing |
|---|---|
|
|
| Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 1.5 times ULN | Withhold until recovery to baseline or less than or equal to 3 times ULN, then resume at reduced dose. |
| ALT or AST elevation greater than 3 times ULN with concurrent total bilirubin elevation greater than 1.5 times ULN (in the absence of cholestasis or hemolysis) | Permanently discontinue. |
| Any grade drug-related interstitial lung disease/pneumonitis | Permanently discontinue. |
| QT corrected for heart rate (QTc) greater than 500 ms on at least 2 separate electrocardiograms (ECGs) | Withhold until recovery to baseline or to a QTc less than 481 ms, then resume at reduced dose. |
| QTc greater than 500 ms or greater than or equal to 60 ms change from baseline with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia | Permanently discontinue. |
| Bradycardia* (symptomatic, may be severe and medically significant, medical intervention indicated) | Withhold until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. Evaluate concomitant medications known to cause bradycardia, as well as antihypertensive medications. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume at reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. |
| Bradycardia*,† (life-threatening consequences, urgent intervention indicated) | Permanently discontinue if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at 250 mg once daily upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoring. |
| Visual Loss (Grade 4 Ocular Disorder) | Discontinue during evaluation of severe vision loss. |
Monitor complete blood counts including differential white blood cell counts monthly and as clinically indicated, with more frequent repeat testing if Grade 3 or 4 abnormalities are observed, or if fever or infection occurs.
