XALKORI® (crizotinib) 2 DOSAGE AND ADMINISTRATION

(crizotinib)

Prescribing Information

2 DOSAGE AND ADMINISTRATION

2.1 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 Clinical Studies (14.1, 14.2, 14.3)].

Information on FDA-approved tests for the detection of ALK and ROS1 rearrangements in NSCLC is available at http://www.fda.gov/companiondiagnostics.

2.2 Recommended Testing During Treatment with XALKORI

•: Monitor liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, every 2 weeks during the first 2 months of treatment, then 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 increased transaminases [see Warnings and Precautions (5.1)].
•: Monitor complete blood counts including differential weekly for the first month of therapy and then at least monthly, with more frequent monitoring if Grade 3 or 4 abnormalities, fever, or infection occur [see Adverse Reactions (6.1)].
•: For pediatric and young adult patients with ALCL or pediatric patients with IMT, obtain baseline and follow-up ophthalmologic examinations including retinal examination within 1 month of starting XALKORI and every 3 months thereafter [see Warnings and Precautions (5.5)].

2.3 Recommended Dosage

The recommended dosage of XALKORI is provided in Table 1.

Table 1. Recommended Dosage of XALKORI
* See Table 2 for Recommended Dosage based on body surface area for pediatric patients and young adults with ALCL for the capsules and oral pellets. † See Table 3 for Recommended Dosage based on body surface area for pediatric patients with IMT for the capsules and oral pellets.
Indication	Recommended Dosage of XALKORI
ALK- or ROS1-Positive Metastatic NSCLC	Adults: 250 mg orally twice daily
Relapsed or Refractory, Systemic ALK-Positive ALCL	Pediatric Patients and Young Adults: 280 mg/m2 orally twice daily*
Unresectable, Recurrent, or Refractory ALK-Positive IMT	Adults: 250 mg orally twice daily
Unresectable, Recurrent, or Refractory ALK-Positive IMT	Pediatric Patients: 280 mg/m2 orally twice daily†

Recommended Dosage for Adult Patients with ALK- or ROS1-Positive Metastatic NSCLC

•: The recommended dosage for adult patients with ALK- or ROS1-positive metastatic NSCLC is XALKORI capsules 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.
•: For adults who cannot swallow capsules, the recommended dosage of XALKORI pellets is 250 mg (2 x 50 mg + 1 x 150 mg) orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.

Recommended Dosage for Pediatric and Young Adult Patients with ALK-Positive ALCL

•: The recommended dosage for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic ALK-positive ALCL is based on body surface area (BSA) and is provided in Table 2.
•: Administer XALKORI capsules or pellets orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.

Table 2 provides the dosage based on body surface area (BSA) for XALKORI capsules or pellets.

Table 2. Recommended XALKORI Dosage for Pediatric Patients 1 Year of Age and Older and Young Adults With ALK-Positive ALCL Using Either XALKORI Capsules or Pellets
* No more than 4 oral pellet shells are to be used for a single dose.
Body Surface Area (BSA)	Recommended XALKORI Dosage to Achieve 280 mg/m2 Twice Daily	Dose Strength Combinations of XALKORI Pellets to Administer*	Dose Strength Combinations of XALKORI Capsules to Administer
0.38 to 0.46 m2	120 mg twice daily	1 x 20 mg + 2 x 50 mg	---
0.47 to 0.51 m2	140 mg twice daily	2 x 20 mg + 2 x 50 mg	---
0.52 to 0.61 m2	150 mg twice daily	1 x 150 mg	---
0.62 to 0.80 m2	200 mg twice daily	1 x 50 mg + 1 x 150 mg	---
0.81 to 0.97 m2	250 mg twice daily	2 x 50 mg + 1 x 150 mg	---
0.98 to 1.16 m2	300 mg twice daily	2 x 150 mg	---
1.17 to 1.33 m2	350 mg twice daily	1 x 50 mg + 2 x 150 mg	---
1.34 to 1.51 m2	400 mg twice daily	2 x 50 mg + 2 x 150 mg	2 x 200 mg
1.52 to 1.69 m2	450 mg twice daily	3 x 150 mg	1 x 200 mg + 1 x 250 mg
1.7 m2 or greater	500 mg twice daily	1 x 50 mg + 3 x 150 mg	2 x 250 mg

Recommended Dosage for Pediatric and Adult Patients with ALK-Positive IMT

•: The recommended dosage for adult patients with unresectable, recurrent, or refractory ALK-positive IMT is provided in Table 1.
•: The recommended dosage for pediatric patients 1 year of age and older with unresectable, recurrent, or refractory ALK-positive IMT is based on BSA and is provided in Table 3.
•: Administer XALKORI capsules or pellets orally twice daily, with or without food, until disease progression or unacceptable toxicity occurs.

Table 3 provides the dosage based on BSA for XALKORI capsules or pellets.

Table 3. Recommended XALKORI Dosage for Pediatric Patients 1 Year of Age and Older with ALK-positive IMT Using Either XALKORI Capsules or Pellets
* No more than 4 oral pellet shells are to be used for a single dose.
Body Surface Area (BSA)	Recommended XALKORI Dosage to Achieve 280 mg/m2 Twice Daily	Dose Strength Combinations of XALKORI Pellets to Administer*	Dose Strength Combinations of XALKORI Capsules to Administer
0.38 to 0.46 m2	120 mg twice daily	1 x 20 mg + 2 x 50 mg	---
0.47 to 0.51 m2	140 mg twice daily	2 x 20 mg + 2 x 50 mg	---
0.52 to 0.61 m2	150 mg twice daily	1 x 150 mg	---
0.62 to 0.80 m2	200 mg twice daily	1 x 50 mg + 1 x 150 mg	---
0.81 to 0.97 m2	250 mg twice daily	2 x 50 mg + 1 x 150 mg	---
0.98 to 1.16 m2	300 mg twice daily	2 x 150 mg	---
1.17 to 1.33 m2	350 mg twice daily	1 x 50 mg + 2 x 150 mg	---
1.34 to 1.51 m2	400 mg twice daily	2 x 50 mg + 2 x 150 mg	2 x 200 mg
1.52 to 1.69 m2	450 mg twice daily	3 x 150 mg	1 x 200 mg + 1 x 250 mg
1.7 m2 or greater	500 mg twice daily	1 x 50 mg + 3 x 150 mg	2 x 250 mg

2.4 Administration

•: Administer XALKORI capsules or pellets orally, twice daily, with or without food.
•: If a dose of XALKORI capsules or pellets is missed, make up that dose unless the next dose is due within 6 hours.
•: If vomiting occurs after taking a dose of XALKORI capsules or pellets, do not take an additional dose. Take the next dose at the regular scheduled time.

XALKORI Capsules

•: Swallow XALKORI capsules whole, with or without food twice daily.
•: Do not chew, crush or split XALKORI capsules.

XALKORI Pellets

•: XALKORI pellets are supplied encapsulated in shells.
•: Do not chew or crush XALKORI pellets.
•: Do not swallow XALKORI pellets encapsulated in the shell.
•: XALKORI pellets can be administered by 2 options:
1.: Open shell(s) containing XALKORI pellets and empty the contents directly into the patient’s mouth.
2.: Open shell(s) containing XALKORI pellets and empty the contents into a consumer-supplied oral dosing aid (e.g., spoon, medicine cup). Administer XALKORI pellets via the dosing aid directly into the patient’s mouth.
•: Immediately after administration, give a sufficient amount of water to ensure that all medication is swallowed.

2.5 Concomitant Treatments for Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT

Antiemetics are recommended prior to and during treatment with XALKORI to prevent nausea and vomiting. Provide standard antiemetic and antidiarrheal agents for gastrointestinal toxicities.

Consider intravenous or oral hydration for patients at risk of dehydration, and replace electrolytes as clinically indicated [see Warnings and Precautions (5.6)].

2.6 Dosage Modifications for Adverse Reactions

The recommended dosage modifications for adverse reactions for adult patients with NSCLC or IMT are provided in Table 4.

Table 4. Recommended Dosage Reductions for Adverse Reactions for Adult Patients with NSCLC or IMT Using XALKORI Capsules or Pellets
Dose Reduction	Dose and Schedule
First Dose Reduction	200 mg twice daily
Second Dose Reduction	250 mg once daily
Permanently discontinue XALKORI capsules or pellets if unable to tolerate 250 mg taken once daily.

The recommended dosage modifications for adverse reactions for pediatric patients with ALCL or IMT and young adults with ALCL are based on body surface area and are provided in Table 5.

Table 5. Recommended Dosage Reductions for Adverse Reactions for Pediatric Patients with ALCL or IMT and Young Adults with ALCL Using XALKORI Capsules or Pellets
* Permanently discontinue in patients who are unable to tolerate XALKORI capsules or pellets after 2 dose reductions.
Body Surface Area (BSA)	First Dose Reduction		Second Dose Reduction*
Body Surface Area (BSA)	Dosage	Dosage Form and Strength to Achieve Recommended Dose Reduction	Dosage	Dosage Form and Strength to Achieve Recommended Dose Reduction
0.38 to 0.46 m2	90 mg twice daily	Pellets: 2 x 20 mg + 1 x 50 mg	70 mg twice daily	Pellets: 1 x 20 mg + 1 x 50 mg
0.47 to 0.51 m2	100 mg twice daily	Pellets: 2 x 50 mg	80 mg twice daily	Pellets: 4 x 20 mg
0.52 to 0.61 m2	120 mg twice daily	Pellets: 1 x 20 mg + 2 x 50 mg	90 mg twice daily	Pellets: 2 x 20 mg + 1 x 50 mg
0.62 to 0.80 m2	150 mg twice daily	Pellets: 1 x 150 mg	120 mg twice daily	Pellets: 1 x 20 mg + 2 x 50 mg
0.81 to 0.97 m2	200 mg twice daily	Pellets: 1 x 50 mg + 1 x 150 mg	150 mg twice daily	Pellets: 1 x 150 mg
0.98 to 1.16 m2	220 mg twice daily	Pellets: 1 x 20 mg + 1 x 50 mg + 1 x 150 mg	170 mg twice daily	Pellets: 1 x 20 mg + 1 x 150 mg
1.17 to 1.33 m2	250 mg twice daily	Pellets: 2 x 50 mg + 1 x 150 mg	200 mg twice daily	Pellets: 1 x 50 mg + 1 x 150 mg
1.34 to 1.69 m2	250 mg twice daily	Pellets: 2 x 50 mg + 1 x 150 mg Or Capsule: 1 x 250 mg	200 mg twice daily	Pellets: 1 x 50 mg + 1 x 150 mg Or Capsule: 1 x 200 mg
1.7 m2 or greater	400 mg twice daily	Pellets: 2 x 50 mg + 2 x 150 mg Or Capsule: 2 x 200 mg	250 mg twice daily	Pellets: 2 x 50 mg + 1 x 150 mg Or Capsule: 1 x 250 mg

Recommended Dosage Modifications for Hematologic Adverse Reactions for Adult Patients with NSCLC or IMT

The recommended dosage modifications for hematologic adverse reactions for adult patients with NSCLC or IMT are provided in Table 6.

Table 6. Adult Patients with NSCLC or IMT: XALKORI Dosage Modification – Hematologic Toxicities*
* Except lymphopenia (unless associated with clinical events, e.g., opportunistic infections). † Grade based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Severity of Adverse Reaction†	XALKORI Dosage Modification
Grade 3	Withhold until recovery to Grade 2 or less, then resume at the same dosage.
Grade 4	Withhold until recovery to Grade 2 or less, then resume at next lower dosage.

Monitor complete blood counts including differential weekly for the first month of therapy and then at least monthly, with more frequent monitoring if Grade 3 or 4 abnormalities, fever, or infection occur.

Recommended Dosage Modifications for Hematologic Adverse Reactions in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT

The recommended dosage modifications for hematologic adverse reactions in pediatric and young adult patients with ALCL or pediatric patients with IMT are provided in Table 7.

Table 7. Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT: XALKORI Dosage Modification for Hematologic Adverse Reactions
* Permanently discontinue in patients who are unable to tolerate XALKORI after 2 dose reductions.
Severity of Adverse Reaction	XALKORI Dosage Modification
Absolute Neutrophil Count (ANC)
Less than 0.5 x 109/L	First occurrence: Withhold until recovery to ANC greater than 1.0 x 109/L, then resume at the next lower dosage. Second occurrence: • Permanently discontinue for recurrence complicated by febrile neutropenia or infection. • For uncomplicated Grade 4 neutropenia, either permanently discontinue, or withhold until recovery to ANC greater than 1.0 x 109/L, then resume at the next lower dosage.*
Platelet Count
25 to 50 x 109/L with concurrent bleeding	Withhold until recovery to platelet count greater than 50 x 109/L and bleeding resolves, then resume at the same dosage.
Less than 25 x 109/L	Withhold until recovery to platelet count greater than 50 x 109/L, then resume at the next lower dosage. Permanently discontinue for recurrence.
Anemia
Hemoglobin less than 8 g/dL	Withhold until recovery to hemoglobin 8 g/dL or more, then resume at the same dosage.
Life-threatening anemia; urgent intervention indicated.	Withhold until recovery to hemoglobin 8 g/dL or more, then resume at the next lower dosage. Permanently discontinue for recurrence.

Recommended Dosage Modifications for Non-Hematologic Adverse Reactions

The recommended dosage modifications for non-hematologic adverse reactions are provided in Table 8.

Table 8. All Patients: XALKORI Dosage Modification for Non-Hematologic Adverse Reactions
* Grade based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. † Adult patients: Heart rate less than 60 beats per minute (bpm); Pediatric patients: Resting heart rate less than the 2.5th percentile per age-specific norms. ‡ Dosage modifications for gastrointestinal toxicity for pediatric patients with ALCL or IMT and young adults with ALCL only. § Permanently discontinue in patients who are unable to tolerate XALKORI after 2 dose reductions.
Severity of Adverse Reaction*	XALKORI Dosage Modification
Hepatotoxicity [see Warnings and Precautions (5.1)]
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 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 next lower dosage.
ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 1.5 times ULN (in the absence of cholestasis or hemolysis)	Permanently discontinue.
Interstitial Lung Disease (Pneumonitis) [see Warnings and Precautions (5.2)]
Any grade drug-related interstitial lung disease/pneumonitis	Permanently discontinue.
QT Interval Prolongation [see Warnings and Precautions (5.3)]
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 next lower dosage.
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 [see Warnings and Precautions (5.4)]
Bradycardia† (symptomatic, may be severe and medically significant, medical intervention indicated)	Withhold until recovery to a resting heart rate according to the patient’s age (based on the 2.5th percentile per age-specific norms) as follows: • 1 to less than 2 years: 91 bpm or above • 2 to 3 years: 82 bpm or above • 4 to 5 years: 72 bpm or above • 6 to 8 years: 64 bpm or above • Older than 8 years: 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 the age-specific heart rate provided above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose adjusted, resume at reduced dose upon recovery to asymptomatic bradycardia or to the age-specific heart rate provided 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 the second dose reduction level in Table 4 or 5 upon recovery to asymptomatic bradycardia or to the heart rate criteria listed for management of symptomatic or severe, medically significant bradycardia, with frequent monitoring. Permanently discontinue for recurrence.
Ocular Toxicity, including Visual Loss [see Warnings and Precautions (5.5)]
Visual Symptoms, Grade 1 (mild symptoms) or Grade 2 (moderate symptoms affecting ability to perform age-appropriate activities of daily living)	Monitor symptoms and report any symptoms to an eye specialist. Consider dose reduction for Grade 2 visual disorders.
Visual Loss (Grade 3 or 4 Ocular Disorder, marked decrease in vision)	Discontinue during evaluation of severe visual loss. Permanently discontinue XALKORI for Grade 3 or 4 ocular disorders or severe visual loss if no other cause found on evaluation.
Gastrointestinal Toxicity‡ [see Warnings and Precautions (5.6)]
Nausea (Grade 3: inadequate oral intake for more than 3 days, medical intervention required)	Grade 3 (despite maximum medical therapy): Withhold until resolved, and then resume at the next lower dose level.§
Vomiting (Grade 3: more than 6 episodes in 24 hours for more than 3 days, medical intervention required, i.e., tube feeding or hospitalization; Grade 4: life-threatening consequences, urgent intervention indicated)	Grade 3 or 4 (despite maximum medical therapy): Withhold until resolved, and then resume at the next lower dose level.§
Diarrhea (Grade 3: increase of 7 or more stools per day over baseline; incontinence; hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated)	Grade 3 or 4 (despite maximum medical therapy): Withhold until resolved, and then resume at the next lower dose level.§

2.7 Dosage Modifications for Moderate and Severe Hepatic Impairment

The recommended dose of XALKORI in patients with moderate hepatic impairment [any aspartate aminotransferase (AST) and total bilirubin greater than 1.5 times the upper limit of normal (ULN) and less than or equal to 3 times ULN] is the first dose reduction shown in Table 4 for adult patients with NSCLC or IMT and Table 5 for pediatric patients with ALCL or IMT and young adults with ALCL [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

The recommended dose of XALKORI in patients with severe hepatic impairment (any AST and total bilirubin greater than 3 times ULN) is the second dose reduction shown in Table 4 for adult patients with NSCLC or IMT and Table 5 for pediatric patients with ALCL or IMT and young adults with ALCL [see Dosage and Administration (2.6), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.8 Dosage Modification for Severe Renal Impairment

The recommended dosage of XALKORI in patients with severe renal impairment [creatinine clearance (CLcr) less than 30 mL/min, calculated using the modified Cockcroft-Gault equation for adult patients and the Schwartz equation for pediatric patients] not requiring dialysis is the second dose reduction shown in Table 4 for adult patients with NSCLC or IMT and Table 5 for pediatric patients with ALCL or IMT and young adults with ALCL [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.9 Dosage Modification for Concomitant Use of Strong CYP3A Inhibitors

Avoid concomitant use of strong CYP3A inhibitors [see Drug Interactions (7.1)]. If concomitant use of strong CYP3A inhibitors is unavoidable, reduce the dose of XALKORI to the second dose reduction shown in Table 4 for adult patients with NSCLC or IMT and Table 5 for pediatric patients with ALCL or IMT and young adults with ALCL. After discontinuation of a strong CYP3A inhibitor, resume the XALKORI dose used prior to initiating the strong CYP3A inhibitor.

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration.				Revised: Sep 2023
MEDICATION GUIDE
XALKORI® (zal-KOR-ee) (crizotinib) capsules		XALKORI® (zal-KOR-ee) (crizotinib) oral pellets
What is the most important information I should know about XALKORI? XALKORI may cause serious side effects, including: • Liver problems. XALKORI may cause life-threatening liver injury that may lead to death. Your healthcare provider should do blood tests to check your liver every 2 weeks during the first 2 months of treatment with XALKORI, then 1 time a month and as recommended by your healthcare provider during treatment. Tell your healthcare provider right away if you develop any of the following new or worsening symptoms:
	o yellowing of your skin or the white part of your eyes o severe tiredness o dark or brown (tea color) urine o nausea or vomiting		o decreased appetite o pain on the right side of your stomach o bleed or bruise more easily than normal o itching
• Lung problems (pneumonitis). XALKORI may cause life-threatening lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms, including: o trouble breathing or shortness of breath o cough with or without mucous o fever • Heart problems. XALKORI may cause very slow, very fast, or abnormal heartbeats. Your healthcare provider may check your pulse rate and blood pressure regularly during treatment with XALKORI. Tell your healthcare provider right away if you feel dizzy or faint or have abnormal heartbeats. Tell your healthcare provider if you take any heart or blood pressure medicines. • Severe vision problems. Vision problems are common with XALKORI. These problems usually happen within 1 week of starting treatment with XALKORI. Vision problems with XALKORI can be severe and may cause partial or complete loss of vision in one or both eyes. Your healthcare provider may hold or permanently stop your treatment with XALKORI and refer you to an eye specialist if any vision problems develop during treatment with XALKORI. Tell your healthcare provider right away if you have any new vision problems, loss of vision or any change in vision, including:
	o double vision o seeing flashes of light o blurry vision		o light hurting your eyes o new or increased floaters
	In addition, for children or young adults taking XALKORI to treat anaplastic large cell lymphoma (ALCL) or children taking XALKORI to treat inflammatory myofibroblastic tumor (IMT): Your healthcare provider may refer you to an eye specialist before starting XALKORI, and within 1 month of starting XALKORI to check for vision problems. You should have an eye examination every 3 months during treatment with XALKORI and more often if there are any new vision problems.
• Severe stomach, intestine, and mouth (gastrointestinal) problems in children or young adults with ALCL or children with IMT. XALKORI may cause severe diarrhea, nausea, vomiting, or mouth sores. Tell your healthcare provider right away if problems with swallowing, vomiting, or diarrhea develop during treatment with XALKORI. o Your healthcare provider may give medicines as needed to prevent or treat diarrhea, nausea, and vomiting. o Your healthcare provider may recommend drinking more fluids or may prescribe electrolyte supplements or other kinds of nutritional support if severe symptoms develop. See "What are possible side effects of XALKORI?" for more information about side effects.
What is XALKORI? XALKORI is a prescription medicine that is used to treat: • adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in either a gene called ALK (anaplastic lymphoma kinase) or a gene called ROS1. • children 1 year of age and older and young adults with ALCL when your ALCL with a defect in a gene called ALK has returned or you have tried a treatment and it did not work or is no longer working. o It is not known if XALKORI is safe and effective in older adults with ALCL. • adults and children 1 year of age and older with IMT when your IMT with a defect in a gene called ALK cannot be removed by surgery, has returned, or you have tried a treatment and it did not work or is no longer working. It is not known if XALKORI is safe and effective in children younger than 1 year of age with ALCL or IMT, or in any children with NSCLC.
Before taking XALKORI, tell your healthcare provider about all of your medical conditions, including if you: • have liver or kidney problems • have lung problems • have heart problems, including a condition called long QT syndrome • have vision or eye problems • are pregnant or plan to become pregnant. XALKORI can harm your unborn baby. Females who are able to become pregnant: o Your healthcare provider will check to see if you are pregnant before starting treatment with XALKORI. o Effective birth control (contraception) should be used during treatment with XALKORI and for 45 days after the last dose of XALKORI. o Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with XALKORI. Males who have female partners who can become pregnant: o You should use condoms during treatment with XALKORI and for 90 days after the last dose of XALKORI. • are breastfeeding or plan to breastfeed. It is not known if XALKORI passes into your breast milk. Do not breastfeed during treatment with XALKORI and for 45 days after the last dose. Talk to your healthcare provider about the best way to feed your baby during this time. Tell your healthcare provider about the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. XALKORI can affect the way other medicines work, and other medicines can affect how XALKORI works.
How should I take XALKORI? • Take XALKORI exactly as prescribed by your healthcare provider. XALKORI comes as capsules and oral pellets. • If your healthcare provider prescribes XALKORI capsules: o Swallow XALKORI capsules whole. Do not chew, crush or split XALKORI capsules. o Take XALKORI capsules with or without food. • If your healthcare provider prescribes XALKORI oral pellets: o See the Instructions for Use at the end of this Medication Guide for instructions about the right way to prepare and give or take XALKORI oral pellets. o XALKORI oral pellets should be poured from the shell(s) directly into the mouth, or given or taken with a spoon or medicine cup. Right after giving or taking the oral pellets, give or drink enough water to make sure all oral pellets are swallowed. o Do not swallow shells containing XALKORI oral pellets. o Do not chew or crush the XALKORI oral pellets. o Take XALKORI oral pellets with or without food. • Your healthcare provider will check your blood cell counts weekly during the first month of treatment with XALKORI and then at least monthly during treatment. • Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with XALKORI if you have certain side effects. Do not change the dose or stop treatment with XALKORI unless your healthcare provider tells you to. • If a dose of XALKORI is missed, it should be taken as soon as you remember. If it is close to the time of the next dose (within 6 hours), the missed dose should be skipped, and the next dose should be taken at the regular time. • If you vomit after taking a dose of XALKORI, do not take an extra dose. The next dose should be taken at the regular time. • XALKORI should be given to children under adult supervision.
What should I avoid while taking XALKORI? • Do not drink grapefruit juice, eat grapefruit or take supplements containing grapefruit extract during treatment with XALKORI. These may increase the amount of XALKORI in the blood. • XALKORI can cause changes in vision, dizziness, and tiredness. Do not drive or operate machinery if you have any of these symptoms. • Avoid spending prolonged time in sunlight. XALKORI can make your skin sensitive to the sun (photosensitivity), and you may burn more easily. You should use sunscreen and wear protective clothing that covers your skin to help protect against sunburn if you have to be in the sunlight during treatment with XALKORI.
What are the possible side effects of XALKORI? XALKORI may cause serious side effects, including: • See "What is the most important information I should know about XALKORI?" The most common side effects of XALKORI in adults with NSCLC include:
• vision problems • nausea, diarrhea, or vomiting • swelling of your hands, feet, face, or eyes • constipation • increased liver function blood tests		• tiredness • decreased appetite • upper respiratory infection • dizziness • feeling of numbness or tingling in your arms or legs
The most common side effects of XALKORI in people with ALCL include:
• diarrhea, vomiting, or nausea • vision problems • headache • muscle and joint pain • mouth sores • tiredness		• decreased appetite • fever • stomach-area (abdominal) pain • cough • itchy skin • low blood counts
The most common side effects of XALKORI in adults with IMT include:
• vision problems • nausea • swelling of your hands, feet, face, or eyes
The most common side effects of XALKORI in children with IMT include:
• vomiting, nausea, or diarrhea • stomach-area (abdominal) pain • rash • vision problems • upper respiratory infection • cough		• fever • muscle and joint pain • tiredness • swelling of your hands, feet, face, or eyes • constipation • headache
XALKORI may cause fertility problems in females and males, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of XALKORI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store XALKORI? • Store XALKORI capsules at room temperature between 68°F to 77°F (20°C to 25°C). • Store XALKORI oral pellets at room temperature between 68°F to 77°F (20°C to 25°C). Keep XALKORI and all medicines out of the reach of children.
General information about the safe and effective use of XALKORI. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XALKORI for a condition for which it was not prescribed. Do not give XALKORI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about XALKORI that is written for health professionals.
What are the ingredients in XALKORI? Active ingredient: crizotinib Capsules inactive ingredients: colloidal silicon dioxide, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate, magnesium stearate, and hard gelatin capsule shells. Pink opaque capsule shell contains: gelatin, titanium dioxide, and red iron oxide. White opaque capsule shell contains: gelatin and titanium dioxide. Printing ink contains: shellac, propylene glycol, strong ammonia solution, potassium hydroxide, and black iron oxide. Oral pellets inactive ingredients: The uncoated pellets contain poloxamer and stearyl alcohol. The film-coating contains hypromellose, glyceryl monostearate, medium chain triglycerides, polyethylene glycol/macrogol, sucrose, and talc. LAB-0441-12.0 For more information, go to www.Pfizer.com or call 1-800-438-1985.

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