Skip to Content

Crizotinib Dosage

Medically reviewed by Drugs.com. Last updated on Dec 15, 2020.

Applies to the following strengths: 250 mg; 200 mg

Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Non-Small Cell Lung Cancer

250 mg orally twice a day

Use: For the treatment of 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

Comments:
-Select patients for the treatment of metastatic NSCLC based on the presence of ALK or ROS1 positivity in tumor specimens.
-Continue treatment until disease progression or unacceptable toxicity.

Usual Pediatric Dose for Lymphoma

280 mg/m2 orally twice a day

Use: 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

Comments:
-The safety and efficacy of this drug have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.
-The safety and effectiveness of this drug in combination with chemotherapy have not been established in patients with newly diagnosed ALCL.
-Continue treatment until disease progression or unacceptable toxicity.
-The recommended dosage of this drug is based on body surface area.
-It may be necessary to combine different strengths of the capsules to obtain the desired dose.
-Antiemetics are recommended prior to and during treatment.
-Provide antiemetic and antidiarrheal agents for gastrointestinal toxicities as appropriate.
-Consider IV or oral hydration therapy for patients at risk of dehydration and administer electrolytes as clinically indicated.

Renal Dose Adjustments

Anaplastic Lymphoma Kinase (ALK) or ROS1-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC):
-Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
-Severe renal dysfunction (CrCl less than 30 mL/min) not requiring dialysis: 250 mg orally once a day

Systemic Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma (ALCL):
-Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
-Severe renal dysfunction (CrCl less than 30 mL/min) not requiring dialysis: Second dose reduction based on body surface area (BSA).

Liver Dose Adjustments

Anaplastic Lymphoma Kinase (ALK) or ROS1-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC):
-Mild liver dysfunction (AST greater than upper limit of normal [ULN] and total bilirubin less than or equal to 1 times ULN or any AST and total bilirubin greater than 1 x ULN but less than or equal to 1.5 x ULN): No adjustment recommended.
-Moderate liver dysfunction (any AST and total bilirubin greater than 1.5 x ULN and less than or equal to 3 x ULN): 200 mg orally twice a day
-Severe liver dysfunction (any AST and total bilirubin greater than 3 x ULN): 250 mg orally once a day

Systemic Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma (ALCL):
-Mild liver dysfunction (AST greater than upper limit of normal [ULN] and total bilirubin less than or equal to 1 times ULN or any AST and total bilirubin greater than 1 x ULN but less than or equal to 1.5 x ULN): No adjustment recommended.
-Moderate liver dysfunction (any AST and total bilirubin greater than 1.5 x ULN and less than or equal to 3 x ULN): First dose reduction based on body surface area (BSA).
-Severe liver dysfunction (any AST and total bilirubin greater than 3 x ULN): Second dose reduction based on BSA.

Dose Adjustments

Anaplastic Lymphoma Kinase (ALK) or ROS1-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC):

Dose modifications for adverse reactions:
-First dose reduction: 200 mg orally twice a day
-Second dose reduction: 250 mg orally once a day
-Permanently discontinue therapy if unable to tolerate 250 mg orally once a day

DOSAGE MODIFICATION FOR HEMATOLOGIC TOXICITIES:
-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.

DOSAGE MODIFICATION FOR NON-HEMATOLOGIC TOXICITIES:
HEPATOTOXICITY:
-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 therapy until recovery to baseline or less than or equal to 3 x ULN, then resume at next lower dosage.
-ALT or AST elevation greater than 3 x ULN with concurrent total bilirubin elevation greater than 1.5 x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue therapy.

INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:
-Any grade drug-related ILD/pneumonitis: Permanently discontinue therapy.

QT PROLONGATION:
-QTc greater than 500 ms on at least 2 separate ECGs: Withhold therapy 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 therapy.

BRADYCARDIA:
-Symptomatic, may be severe and medically significant, medical intervention indicated: Withhold therapy until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above; if concomitant medication contributing to bradycardia is identified and it's discontinued or dose adjusted, resume therapy at previous dose; if no contributing medication is identified or that medication is not discontinued or dose adjusted, resume therapy at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
-Life-threatening, urgent intervention indicated: Permanently discontinue therapy if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued or its dose is adjusted, resume therapy at 250 mg once a day upon recovery to asymptomatic or to a heart rate of 60 bpm or grater with frequent monitoring. In case of recurrence, permanently discontinue therapy.

SEVERE VISION LOSS (GRADE 4 OCULAR DISORDER): Discontinue therapy during evaluation of severe vision loss.

Dosage Modification for Concomitant Use of Strong CYP450 3A Inhibitors:
-Avoid concomitant use of strong CYP450 3A inhibitors; if concomitant use is unavoidable, reduce the dose of crizotinib to 250 mg orally once daily.
-After discontinuation of a strong CYP450 3A inhibitor, resume the crizotinib dose used prior to initiating the strong CYP450 3A inhibitor.

Systemic Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma (ALCL):

Recommended Dosage Based on Body Surface Area (BSA) and Dose Modification for ALCL Adverse Dose Reactions:
Less than 0.60 m2: Not established
0.60 to 0.80 m2: 200 mg orally twice a day
-First dose reduction: 250 mg once a day
-Second dose reduction: Permanently discontinue
0.81 to 1.16 m2: 250 mg orally twice a day
-First dose reductions: 200 mg twice a day
-Second dose reduction: 250 mg once a day; permanently discontinue if unable to tolerate
1.17 to 1.51 m2: 400 mg orally twice a day
-Firs dose reduction: 250 mg twice a day
-Second dose reduction: 200 mg twice a day; permanently discontinue if unable to tolerate
1.52 to 1.69 m2: 450 mg orally twice a day
-Firs dose reduction: 250 mg twice a day
-Second dose reduction: 200 mg twice a day; permanently discontinue if unable to tolerate
1.70 m2 or greater: 500 mg orally twice a day
-First dose reduction: 400 mg twice a day
-Second dose reduction 250 mg twice a day; permanently discontinue if unable to tolerate

DOSAGE MODIFICATION FOR HEMATOLOGIC ADVERSE REACTIONS:
ABSOLUTE NEUTROPHIL COUNT (ANC):
If less than 0.5 x 10(9)/L:
-First occurrence: Withhold until recovery to ANC greater than 1 x 10(9)/L and resume at next lower dosage.
-Second occurrence: Permanently discontinue for recurrence complicated by febrile neutropenia or infection and if uncomplicated Grade 4 neutropenia, either permanently discontinue, or withhold until recovery to ANC greater than 1 x 10(9)/L and resume at next lower dosage or may permanently discontinue if unable to tolerate.

PLATELET COUNT:
-If 25 to 50 x 10(9)/L with bleeding: Withhold until recovery to platelet count greater than 50 x 10(9)/L and bleeding resolves; resume at the same dosage.
-If less than 25 x 10(9)/L: Withhold until recovery to platelet count greater than 50 x 10(9)/L and resume at next lower dosage; permanently discontinue for recurrence.

ANEMIA:
-If hemoglobin less than 8 g/dL: Withhold until recovery to 8 g/dL or more, then resume at same dosage.
-If life-threatening anemia; urgent intervention indicated: Withhold until recovery to 8 g/dL, then resume at next lower dosage; permanently discontinue for recurrence.

DOSAGE MODIFICATION FOR NON-HEMATOLOGIC TOXICITIES:
HEPATOTOXICITY:
-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 therapy until recovery to baseline or less than or equal to 3 x ULN, then resume at next lower dosage.
-ALT or AST elevation greater than 3 x ULN with concurrent total bilirubin elevation greater than 1.5 x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue therapy.

INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:
-Any grade drug-related ILD/pneumonitis: Permanently discontinue therapy.

QT PROLONGATION:
-QTc greater than 500 ms on at least 2 separate ECGs: Withhold therapy 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 therapy.

BRADYCARDIA:
Symptomatic, may be severe and medically significant, medical intervention indicated:
-Withhold therapy until recovery to a resting heart rate according to the patient's age (based on the 2.5th percentile per age-specific norms) as such:
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
Greater than 8 year: 60 bpm or above
-Life-threatening, urgent intervention indicated: Permanently discontinue therapy if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued or its dose is adjusted, resume therapy at the second dose reduction level upon recovery to asymptomatic or to the above-mentioned heart rate criteria with frequent monitoring.

OCULAR TOXICITY, INCLUDING VISUAL LOSS:
-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 disturbances.
-Visual loss (Grade 3 or 4 ocular disorder, marked decrease in vision): Withhold pending evaluation of severe visual loss. Permanently discontinue for Grade 3 or 4 if no other cause found on evaluation

GASTROINTESTINAL TOXICITY:
Nausea:
-For Grade 3 (inadequate oral intake for more than 3 days, medical intervention required) despite maximum medical treatment: Withhold until resolved, and then resume at the next lower dose level.

Vomiting:
-For Grade 3 (more than 6 episodes in 24 hours for more than 3 days, medical intervention required, e.g., tube feeding or hospitalization) or Grade 4 (life-threatening consequences, urgent intervention indicated) despite maximum medical treatment: Withhold until resolved, and then resume at the next lower dose level.

Diarrhea:
-For Grade 3 (increase of 7 or more stools per day over baseline; incontinence; hospitalization indicated) or Grade 4 (life-threatening consequences, urgent intervention indicated): Withhold until resolved; then resume at the next lower dose level or may permanently discontinue if unable to tolerate. Permanently discontinue for recurrence.

Dosage Modification for Concomitant Use of Strong CYP450 3A Inhibitors:
-Avoid concomitant use of strong CYP450 3A inhibitors; if concomitant use is unavoidable, reduce the dose of crizotinib to the second dose reduction based on BSA.
-After discontinuation of a strong CYP450 3A inhibitor, resume the crizotinib dose used prior to initiating the strong CYP450 3A inhibitor.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in pediatric patients younger than 12 months of age with anaplastic large cell lymphoma or in any pediatric patient with non-small cell lung cancer.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
-Take with or without food.
-Swallow capsules whole.
-Make up a missed dose unless the next dose is due within 6 hours.
-If vomiting occurs after taking a dose, take the next dose at the regular time.
-Evaluate pediatric patients for ability to swallow intact capsules.
-Administer this drug to pediatric patients under adult supervision.
-Consider the administration of antiemetics prior to and during treatment if appropriate.
-Provide antiemetic and antidiarrheal agents for gastrointestinal toxicities as needed.
-Consider IV or oral hydration therapy for patients at risk of dehydration and administer electrolytes as clinically indicated.
-Preparation, handling, and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.

General:
-Selection of patients is based on the presence of anaplastic lymphoma kinase (ALK) positivity in tumor specimens as detected by a well-validated test.

Monitoring:
-For the treatment of non-small cell lung cancer 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.
-For the treatment of anaplastic large cell lymphoma monitor complete blood counts including differential white blood cell counts weekly for the first month and then at least monthly, with more frequent monitoring if Grade 3 or 4 abnormalities, fever, or infection occur.
-Monitor heart rate and blood pressure regularly, as appropriate.
-Obtain ECGs and electrolytes as close as possible prior to the first dose and periodic monitoring in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, history or predisposition for QTc prolongation, and taking medications that prolong the QT interval.
-Monitor with liver function tests including ALT, AST, and total bilirubin every two weeks during the first 2 months of treatment, then once a month and as clinically indicated.
-Monitor patients for pulmonary symptoms indicative of interstitial lung disease/pneumonitis.
-Monitor for symptoms of ocular toxicity, including visual loss.
-Monitor for gastrointestinal (GI) toxicities and GI perforation appropriate.

Patient advice:
-Take with or without food.
-Swallow capsules whole.
-This drug should be given to children under adult supervision.
-Make up a missed dose unless the next dose is due within 6 hours.
-If vomiting occurs after taking a dose, take the next dose at the regular time.
-Avoid grapefruit or grapefruit juice while taking this drug.
-Inform your healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.
-Females should not breastfeed during therapy and for 45 days after.
-Fetal harm may occur with this drug; avoid pregnancy during therapy.
-Confirm pregnancy status prior to initiating treatment.
-Females of reproductive potential should use effective contraception during therapy and for at least 45 days after the final dose.
-Males with female partners of reproductive potential should use condoms during therapy and for at least 90 days after the final dose.
-If pregnancy occurs, contact your healthcare provider immediately.
-Inform females and males of reproductive potential of the potential for reduced fertility.
-Immediately report symptoms of hepatotoxicity to your healthcare provider.
-Immediately report any new or worsening pulmonary symptoms to your healthcare provider.
-Report any symptoms of bradycardia and inform your healthcare provider about the use of any heart or blood pressure medications.
-Immediately contact your healthcare provider if you develop severe visual loss or change in vision such as perceived flashes of light, blurry vision, light sensitivity, and floaters.
-Inform patients with ALCL or caregivers to immediately report problems with swallowing, vomiting, or diarrhea.
-Advise patients of the first signs of gastrointestinal perforations.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.