Xalkori
(Crizotinib)Dosage & Administration
Xalkori Prescribing Information
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 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.
The recommended dosage of XALKORI is provided in Table 1.
Recommended Dosage for Adult Patients with ALK- or ROS1-Positive Metastatic NSCLC
Recommended Dosage for Pediatric and Young Adult Patients with ALK-Positive ALCL
Table 2 provides the dosage based on body surface area (BSA) for XALKORI capsules or pellets.
Recommended Dosage for Pediatric and Adult Patients with ALK-Positive IMT
Table 3 provides the dosage based on BSA for XALKORI capsules or pellets.
XALKORI Capsules
XALKORI Pellets
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)] .The recommended dosage modifications for adverse reactions for adult patients with NSCLC or IMT are provided in Table 4.
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.
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.
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.
Recommended Dosage Modifications for Non-Hematologic Adverse Reactions The recommended dosage modifications for non-hematologic adverse reactions are provided in Table 8.
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)] .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)] .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. | 9/2023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
XALKORI is a kinase inhibitor indicated for the treatment of
• adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. (,1.1 ALK- or ROS1-Positive Metastatic Non-Small Cell Lung CancerXALKORI is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test
[see Dosage and Administration (2.1)].)2.1 Patient SelectionSelect 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.
• pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. (,1.2 Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell LymphomaXALKORI is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive
.Limitations of Use: The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.)2.3 Recommended DosageThe recommended dosage of XALKORI is provided in Table 1.
Table 1. Recommended Dosage of XALKORI IndicationRecommended Dosage of XALKORIALK- or ROS1-Positive Metastatic NSCLCAdults:
250 mg orally twice dailyRelapsed or Refractory, Systemic ALK-Positive ALCLPediatric Patients and Young Adults:
280 mg/m2orally twice dailySee Table 2 for Recommended Dosage based on body surface area for pediatric patients and young adults with ALCL for the capsules and oral pellets.Unresectable, Recurrent, or Refractory ALK-Positive IMTAdults:
250 mg orally twice dailyPediatric Patients:
280 mg/m2orally twice dailySee Table 3 for Recommended Dosage based on body surface area for pediatric patients with IMT for the capsules and oral pellets.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 Body Surface Area (BSA)Recommended XALKORI Dosage to Achieve 280 mg/m2Twice DailyDose Strength Combinations of XALKORI Pellets to AdministerNo more than 4 oral pellet shells are to be used for a single dose.Dose Strength Combinations of XALKORI Capsules to Administer0.38 to 0.46 m2120 mg twice daily1 x 20 mg + 2 x 50 mg---0.47 to 0.51 m2140 mg twice daily2 x 20 mg + 2 x 50 mg---0.52 to 0.61 m2150 mg twice daily1 x 150 mg---0.62 to 0.80 m2200 mg twice daily1 x 50 mg + 1 x 150 mg---0.81 to 0.97 m2250 mg twice daily2 x 50 mg + 1 x 150 mg---0.98 to 1.16 m2300 mg twice daily2 x 150 mg---1.17 to 1.33 m2350 mg twice daily1 x 50 mg + 2 x 150 mg---1.34 to 1.51 m2400 mg twice daily2 x 50 mg + 2 x 150 mg2 x 200 mg1.52 to 1.69 m2450 mg twice daily3 x 150 mg1 x 200 mg + 1 x 250 mg1.7 m2or greater500 mg twice daily1 x 50 mg + 3 x 150 mg2 x 250 mgRecommended 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 Body Surface Area (BSA)Recommended XALKORI Dosage to Achieve 280 mg/m2Twice DailyDose Strength Combinations of XALKORI Pellets to AdministerNo more than 4 oral pellet shells are to be used for a single dose.Dose Strength Combinations of XALKORI Capsules to Administer0.38 to 0.46 m2120 mg twice daily1 x 20 mg + 2 x 50 mg---0.47 to 0.51 m2140 mg twice daily2 x 20 mg + 2 x 50 mg---0.52 to 0.61 m2150 mg twice daily1 x 150 mg---0.62 to 0.80 m2200 mg twice daily1 x 50 mg + 1 x 150 mg---0.81 to 0.97 m2250 mg twice daily2 x 50 mg + 1 x 150 mg---0.98 to 1.16 m2300 mg twice daily2 x 150 mg---1.17 to 1.33 m2350 mg twice daily1 x 50 mg + 2 x 150 mg---1.34 to 1.51 m2400 mg twice daily2 x 50 mg + 2 x 150 mg2 x 200 mg1.52 to 1.69 m2450 mg twice daily3 x 150 mg1 x 200 mg + 1 x 250 mg1.7 m2or greater500 mg twice daily1 x 50 mg + 3 x 150 mg2 x 250 mgo Limitations of Use: The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.
• adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. (,1.3 Unresectable, Recurrent, or Refractory ALK-Positive Inflammatory Myofibroblastic TumorXALKORI is indicated for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.
)2.3 Recommended DosageThe recommended dosage of XALKORI is provided in Table 1.
Table 1. Recommended Dosage of XALKORI IndicationRecommended Dosage of XALKORIALK- or ROS1-Positive Metastatic NSCLCAdults:
250 mg orally twice dailyRelapsed or Refractory, Systemic ALK-Positive ALCLPediatric Patients and Young Adults:
280 mg/m2orally twice dailySee Table 2 for Recommended Dosage based on body surface area for pediatric patients and young adults with ALCL for the capsules and oral pellets.Unresectable, Recurrent, or Refractory ALK-Positive IMTAdults:
250 mg orally twice dailyPediatric Patients:
280 mg/m2orally twice dailySee Table 3 for Recommended Dosage based on body surface area for pediatric patients with IMT for the capsules and oral pellets.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 Body Surface Area (BSA)Recommended XALKORI Dosage to Achieve 280 mg/m2Twice DailyDose Strength Combinations of XALKORI Pellets to AdministerNo more than 4 oral pellet shells are to be used for a single dose.Dose Strength Combinations of XALKORI Capsules to Administer0.38 to 0.46 m2120 mg twice daily1 x 20 mg + 2 x 50 mg---0.47 to 0.51 m2140 mg twice daily2 x 20 mg + 2 x 50 mg---0.52 to 0.61 m2150 mg twice daily1 x 150 mg---0.62 to 0.80 m2200 mg twice daily1 x 50 mg + 1 x 150 mg---0.81 to 0.97 m2250 mg twice daily2 x 50 mg + 1 x 150 mg---0.98 to 1.16 m2300 mg twice daily2 x 150 mg---1.17 to 1.33 m2350 mg twice daily1 x 50 mg + 2 x 150 mg---1.34 to 1.51 m2400 mg twice daily2 x 50 mg + 2 x 150 mg2 x 200 mg1.52 to 1.69 m2450 mg twice daily3 x 150 mg1 x 200 mg + 1 x 250 mg1.7 m2or greater500 mg twice daily1 x 50 mg + 3 x 150 mg2 x 250 mgRecommended 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 Body Surface Area (BSA)Recommended XALKORI Dosage to Achieve 280 mg/m2Twice DailyDose Strength Combinations of XALKORI Pellets to AdministerNo more than 4 oral pellet shells are to be used for a single dose.Dose Strength Combinations of XALKORI Capsules to Administer0.38 to 0.46 m2120 mg twice daily1 x 20 mg + 2 x 50 mg---0.47 to 0.51 m2140 mg twice daily2 x 20 mg + 2 x 50 mg---0.52 to 0.61 m2150 mg twice daily1 x 150 mg---0.62 to 0.80 m2200 mg twice daily1 x 50 mg + 1 x 150 mg---0.81 to 0.97 m2250 mg twice daily2 x 50 mg + 1 x 150 mg---0.98 to 1.16 m2300 mg twice daily2 x 150 mg---1.17 to 1.33 m2350 mg twice daily1 x 50 mg + 2 x 150 mg---1.34 to 1.51 m2400 mg twice daily2 x 50 mg + 2 x 150 mg2 x 200 mg1.52 to 1.69 m2450 mg twice daily3 x 150 mg1 x 200 mg + 1 x 250 mg1.7 m2or greater500 mg twice daily1 x 50 mg + 3 x 150 mg2 x 250 mg
Capsules:
• 200 mg: hard gelatin capsule, size 1, white opaque body and pink opaque cap, with "Pfizer" on the cap and "CRZ 200" on the body.• 250 mg: hard gelatin capsule, size 0, pink opaque cap and body, with "Pfizer" on the cap and "CRZ 250" on the body.
Oral Pellets:
• 20 mg: hard gelatin capsule, size 4, white opaque body and light blue opaque cap, printed with black ink “Pfizer” on the cap and “CRZ 20” on the body.• 50 mg: hard gelatin capsule, size 3, light gray opaque body and gray opaque cap, printed with black ink “Pfizer” on the cap and “CRZ 50” on the body.• 150 mg: hard gelatin capsule, size 0, light blue opaque body and cap, printed with black ink “Pfizer” on the cap and “CRZ 150” on the body.
Lactation: Advise not to breastfeed. (
There is no information regarding the presence of crizotinib or its metabolites in human milk, or the effects on the breastfed child or on milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with XALKORI and for 45 days after the last dose.
None.