Xalkori Dosage/Direction for Use

Recommended Dose: ALK and ROS1 Testing: An accurate and validated assay for either ALK or ROS1 is necessary for the selection of patients for treatment with crizotinib.
Either ALK-positive or ROS1-positive NSCLC status should be established prior to initiation of crizotinib therapy. Assessment should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance can lead to unreliable test results.
Recommended Dosing: The recommended dose schedule of crizotinib is 250 mg taken orally twice daily. Continue treatment as long as the patient is deriving clinical benefit from therapy. Crizotinib may be taken with or without food (see Pharmacology: Pharmacokinetics under Actions). Capsules should be swallowed whole. If a dose of crizotinib is missed, then it should be taken as soon as the patient remembers unless it is less than 6 hours until the next dose, in which case the patient should not take the missed dose. Patients should not take 2 doses at the same time to make up for a missed dose.
Dose Modification: Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary for patients treated with crizotinib 250 mg orally twice daily, then the dose of crizotinib should be reduced as follows.
First dose reduction: crizotinib 200 mg taken orally twice daily.
Second dose reduction: crizotinib 250 mg taken orally once daily.
Permanently discontinue if unable to tolerate crizotinib 250 mg taken orally once daily.
Dose reduction guidelines for hematologic and non-hematologic toxicities are provided in Table 5 and Table 6. For patients treated with a lower dose of crizotinib than 250 mg twice daily, then use the recommendations in Table 5 and Table 6 accordingly. (See Tables 5 and 6.)

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Hepatic impairment: Crizotinib is extensively metabolized in the liver. Treatment with crizotinib should be used with caution in patients with hepatic impairment (see Table 6 and Pharmacology: Pharmacokinetics under Actions and Precautions).
A clinical study was conducted in patients with advanced cancer and varying degrees of hepatic impairment, based on National Cancer Institute (NCI) classification, who received multiple doses of crizotinib to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of crizotinib. No starting dose adjustment of crizotinib is recommended for patients with mild hepatic impairment (either AST > Upper Limit of Normal (ULN) and total bilirubin ≤ULN or any AST and total bilirubin >ULN but ≤1.5xULN), as the systemic crizotinib exposure was comparable to that from patients with normal hepatic function receiving the same crizotinib dose of 250 mg twice daily. The starting crizotinib dose for patients with moderate hepatic impairment (any AST and total bilirubin >1.5xULN and ≤3xULN) is recommended to be 200 mg twice daily, as the systemic crizotinib exposure increased compared to that from patients with normal hepatic function receiving the same dose of 200 mg twice daily, but was comparable to that from patients with normal hepatic function receiving 250 mg twice daily. The starting crizotinib dose for patients with severe hepatic impairment (any AST and total bilirubin >3xULN) is recommended to be 250 mg once daily, as crizotinib doses greater than 250 mg once daily have not been studied in patients with severe hepatic impairment and may result in increases of systemic crizotinib exposure to supra-therapeutic levels.
Renal impairment: No starting dose adjustment is needed for patients with mild (60 ≤ creatinine clearance [CL_cr] < 90 mL/min) or moderate renal impairment (30 ≤ CL_cr < 60 mL/min), since the population pharmacokinetic analysis indicated no clinically meaningful changes in steady-state crizotinib exposure in these patients. Crizotinib plasma concentrations may be increased in patients with severe renal impairment (CL_cr < 30 mL/min). The crizotinib dose should be adjusted to 250 mg taken orally once daily in patients with severe renal impairment not requiring peritoneal dialysis or hemodialysis. The dose may be increased to 200 mg twice daily based on individual safety and tolerability after at least 4 weeks of treatment (see Pharmacology: Pharmacokinetics under Actions and Precautions).
Pediatric patients: The safety and efficacy of crizotinib in pediatric patients has not been established.
Elderly: No starting dose adjustment is required (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Mode of Administration: Oral administration.