Adult Dosing
Locally advanced or metastatic non-small cell lung cancer (NSCLC)
- Recommended dose: 250 mg PO bid
Note:
- Continue therapy until the patient is gaining clinical benefit from this product
- Do not crush, cut, dissolve, or open capsules; swallow them whole
- Advise patients not to take the missed dose if it is <6 hrs until the next dose. Instruct them to avoid taking 2 doses at the same time to make up for a missed dose
- Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, reduce the dose to 200 mg PO twice daily. If further dose reduction is required, then reduce the dose to 250 mg PO once daily based on individual safety and tolerability
- Adjust dose based on hematologic and non-hematologic toxicities
- Monitor CBC including differential white blood cell counts and liver function tests monthly and as clinically indicated during therapy
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustments (Based on CrCl)
- Mild renal impairment (60-90 mL/min): No dose adjustments
- Moderate renal impairment (30-60 mL/min): No dose adjustments
- Severe renal impairment (<30 mL/min) or end-stage renal disease: 250 mg PO qd
Hepatic Dose Adjustments
- Hepatic impairment: Dose adjustments not defined; use with caution
See Supplemental Patient Information
- Therapy may be associated with severe, life-threatening, or fatal treatment-related pneumonitis; such events occurred within 2 months after therapy initiation. Monitor patients for pulmonary symptoms indicative of pneumonitis. Exclude other causes of pneumonitis, and permanently discontinue therapy in patients diagnosed with treatment-related pneumonitis
- Drug-induced hepatotoxicity with fatal outcome has been reported. Grade 3 or 4 ALT elevations may occur; these elevations may be asymptomatic and reversible upon interruption of treatment. Treatment may be resumed at a lower dose without recurrence; however, permanent treatment discontinuation may be required in certain patients. Concurrent elevations in ALT >3x ULN and total bilirubin >2x ULN with normal alkaline phosphatase have been reported. Monitor LFTs 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 with elevated transaminases
- QTc prolongation may occur. Avoid therapy in patients with congenital long QT syndrome. Consider periodic monitoring with ECGs and electrolytes in patients with bradyarrhythmias, CHF, electrolyte abnormalities, or those receiving medications which prolong the QT interval. Permanently discontinue therapy in patients who experience Grade 4 QTc prolongation. Withhold therapy in patients who develop Grade 3 QTc prolongation until recovery to
Grade 1, and then resume at 200 mg bid. On recurrence of Grade 3 QTc prolongation, withhold therapy until recovery to Grade 1 and then resume at 250 mg PO qd. Discontinue therapy permanently on recurrence of Grade 3 QTc prolongation - For selection of patients for therapy with crizotinib, detection of ALK-positive NSCLC using an FDA-approved test is recommended. Perform assessment for ALK-positive NSCLC in laboratories with demonstrated proficiency in the specific technology being utilized, as improper assay performance may lead to unreliable test results
- Therapy may cause fetal harm when administered to a pregnant woman. Advise women of childbearing potential to avoid becoming pregnant while receiving this drug. Apprise the patient of the potential hazard to a fetus if used during pregnancy or if the patient becomes pregnant while taking this drug
Cautions: Use cautiously in
- Hepatic impairment
- Renal impairment (CrCl <30)
- QT prolongation risk
Supplemental Patient Information
- Advise patients to refrain from driving, operating machinery, or any other potentially hazardous task during therapy due to the potential for dizziness, fatigue, or vision disorder
- Inform patients to avoid grapefruit or grapefruit juice during therapy
- Instruct patients of childbearing potential to use appropriate contraceptive methods during therapy and for at least 90 days after treatment. Also, advise patients not to breastfeed during therapy
Pregnancy Category:D
Breastfeeding: It is unknown whether crizotinib is excreted in breast milk. According to the manufacturer’s data, a decision should be made whether to discontinue nursing or to discontinue the drug, analyzing the importance of the drug to the mother.
