"The U.S. Food and Drug Administration today approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, a"...
ALK-Positive Metastatic NSCLC
XALKORI is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test [see Clinical Studies].
ROS1-Positive Metastatic NSCLC
XALKORI is indicated for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive [see Clinical Studies].
DOSAGE AND ADMINISTRATION
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 and Clinical Studies].
Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm.
An FDA-approved test for the detection of ROS1 rearrangements in NSCLC is not currently available. Refer to Section 14.2 for information on the tests used in the clinical study to identify patients with ROS1 rearrangements in NSCLC.
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 severe renal impairment [creatinine clearance (CLcr) < 30 mL/min] not requiring dialysis is 250 mg orally, once daily [see Use in Specific Populations and CLINICAL PHARMACOLOGY].
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.
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.
Table 1: XALKORI Dose Modification – Hematologic
|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|
|a Except lymphopenia (unless associated with clinical events, e.g., opportunistic infections).|
Table 2: XALKORI Dose
Modification – Non-Hematologic Toxicities
|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.|
|Bradycardiaa (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.
|Bradycardiaa,b (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.|
|a Heart rate less than 60 beats per minute
b Permanently discontinue for recurrence.
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.
Dosage Forms And Strengths
- 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.
Storage And Handling
250 mg Capsules
Hard gelatin capsule with pink opaque cap and body, printed with black ink “Pfizer” on the cap, “CRZ 250” on the body; available in:
Bottles of 60 capsules: NDC 0069-8140-20
200 mg Capsules
Hard gelatin capsule with pink opaque cap and white opaque body, printed with black ink “Pfizer” on the cap, “CRZ 200” on the body; available in:
Bottles of 60 capsules: NDC 0069-8141-20
Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Distributed by: Pfizer Labs, Division of Pfizer Inc., NY, NY 10017. Revised: March 2016This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/9/2016
Additional Xalkori Information
Report Problems to the Food and Drug Administration
Get the latest treatment options.