XALKORI- crizotinib capsule
Pfizer Laboratories Div Pfizer Inc
XALKORI is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.
This indication is based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with XALKORI.
The recommended dose and schedule of XALKORI is 250 mg taken orally twice daily. Continue treatment as long as the patient is deriving clinical benefit from therapy. 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.
Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, then reduce the dose of XALKORI to 200 mg taken orally twice daily. If further dose reduction is necessary, then reduce the dosage to 250 mg taken orally once daily. Dose reduction guidelines for hematologic and non-hematologic toxicities are provided in Tables 1 and 2.
|CTCAE † Grade||XALKORI Dosing|
|Grade 3||Withhold until recovery to Grade ≤2, then resume at the same dose schedule|
|Grade 4||Withhold until recovery to Grade ≤2, then resume at 200 mg twice daily ‡|
|CTCAE Grade||XALKORI Dosing|
|Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation with Grade ≤1 total bilirubin||Withhold until recovery to Grade ≤1 or baseline, then resume at 200 mg twice daily *|
|Grade 2, 3 or 4 ALT or AST elevation with concurrent Grade 2, 3 or 4 total bilirubin elevation (in the absence of cholestasis or hemolysis)||Permanently discontinue|
|Any Grade pneumonitis †||Permanently discontinue|
|Grade 3 QTc prolongation||Withhold until recovery to Grade ≤1, then resume at 200 mg twice daily *|
|Grade 4 QTc prolongation||Permanently discontinue|
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. Monitor liver function tests monthly and as clinically indicated, with more frequent repeat testing if Grade 2, 3 or 4 abnormalities are observed.
250 mg capsules
Hard gelatin capsule, size 0, pink opaque cap and body, with "Pfizer" on the cap and "CRZ 250" on the body.
200 mg capsules
Hard gelatin capsule, size 1, white opaque body and pink opaque cap, with "Pfizer" on the cap and "CRZ 200" on the body.
Drug-induced hepatotoxicity with fatal outcome has occurred. These cases have occurred during XALKORI treatment in less than 1% of patients in clinical trials. Concurrent elevations in ALT greater than 3 times the upper limit of normal and total bilirubin greater than 2 times the upper limit of normal, with normal alkaline phosphatase, occurred in less than 1% of patients in clinical trials. Elevation in ALT greater than 5 times the upper limit of normal occurred in 7% of patients in Study A and in 4% of patients in Study B. These laboratory findings were generally asymptomatic and reversible upon dosing interruption. Patients usually resumed treatment at a lower dose without recurrence; however, 3 patients from Study A (2%) and 1 patient from Study B (less than 1%) required permanent discontinuation from treatment. Transaminase elevations generally occurred within the first 2 months of treatment. Monitor with liver function tests including ALT and total bilirubin once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations [see Dosage and Administration (2.2) and Adverse Reactions (6)].
XALKORI has been associated with severe, life-threatening, or fatal treatment-related pneumonitis in clinical trials with a frequency of 4 in 255 (1.6%) patients across Studies A and B. All of these cases occurred within 2 months after the initiation of treatment. Monitor patients for pulmonary symptoms indicative of pneumonitis. Exclude other causes of pneumonitis, and permanently discontinue XALKORI in patients diagnosed with treatment-related pneumonitis [see Dosage and Administration (2.2)].
QTc prolongation has been observed. Avoid use of XALKORI in patients with congenital long QT syndrome. Consider periodic monitoring with electrocardiograms (ECGs) and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QT interval. Permanently discontinue XALKORI in patients who develop Grade 4 QTc prolongation. Withhold XALKORI in patients who develop Grade 3 QTc prolongation until recovery to less than or equal to Grade 1, then resume XALKORI at 200 mg twice daily. In case of recurrence of Grade 3 QTc prolongation, withhold XALKORI until recovery to less than or equal to Grade 1, then resume XALKORI at 250 mg once daily. Permanently discontinue XALKORI if Grade 3 QTc prolongation recurs [see Dosage and Administration (2.2) and Clinical Pharmacology (12.4)].
Detection of ALK-positive NSCLC using an FDA-approved test, indicated for this use, is necessary for selection of patients for treatment with XALKORI [see Clinical Studies (14)].
Assessment for ALK-positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance can lead to unreliable test results.
Refer to an FDA-approved test's package insert for instructions on the identification of patients eligible for treatment with XALKORI.