Usual Adult Dose for Non-Small Cell Lung Cancer

450 mg orally once daily at the same time each day until disease progression or unacceptable toxicity

Use: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib

Renal Dose Adjustments

Mild to moderate renal impairment (CrCl 30 to less than 90 mL/min): No adjustment recommended.
Severe renal impairment (CrCl less than 30 mL/min): Data not available

Liver Dose Adjustments

Mild hepatic impairment (Child-Pugh A or B): No adjustment recommended.
Severe hepatic impairment (Child-Pugh C): Reduce dose by approximately one-third, rounded to the nearest multiple of the 150 mg dose strength.

Dose Adjustments

DOSE MODIFICATIONS:

• First dose reduction: 300 mg once a day
• Second dose reduction: 150 mg once a day
• Discontinue this drug in patients unable to tolerate 150 mg daily.

• Severe or intolerable nausea, vomiting, or diarrhea despite antiemetic or antidiarrheal therapy: Withhold therapy until improved; resume at the next lower dose.

• ALT or AST elevation greater than 5 times upper limit of normal (ULN) with total bilirubin elevation less than or equal to 2 x ULN: Withhold therapy until recovery to baseline or less than or equal to 3 x ULN; resume at the next lower dose.
• ALT or AST elevation greater than 3 x ULN with total bilirubin elevation greater than 2 x ULN in the absence of cholestasis or hemolysis: Permanently discontinue therapy.

• Any Grade therapy-related ILD/pneumonitis: Permanently discontinue therapy.

• QTc interval greater than 500 msec on at least 2 separate ECGs: Withhold therapy until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec; resume at the next lower dose.
• QTc interval prolongation in combination with Torsades de pointes or polymorphic ventricular tachycardia or serious arrhythmia: Permanently discontinue therapy.

• Persistent hyperglycemia greater than 250 mg/dL despite antihyperglycemic therapy: Withhold therapy until hyperglycemia is adequately controlled; resume at the next lower dose; if adequate hyperglycemic control cannot be achieved with medical management, discontinue this drug.

• Symptomatic bradycardia that is not life-threatening: Withhold therapy until recovery to asymptomatic bradycardia or to heart rate of 60 bpm or above, evaluate concomitant medications known to cause bradycardia; if bradycardia cannot be attributed to another drug, resume therapy at the next lower dose.
• Clinically significant bradycardia requiring intervention or life-threatening bradycardia in patients taking a concomitant medication also known to cause bradycardia or a medication known to cause hypotension: Permanently discontinue therapy.

• Lipase or amylase elevation greater than 2 x ULN: Withhold therapy until recovery to less than 1.5 x ULN; resume at the next lower dose.

• Avoid use if possible.
• If use cannot be avoided, reduce dose of ceritinib by approximately one-third rounded to the nearest multiple of the 150 mg.
• After discontinuation of a strong CYP450 3A inhibitor, resume the ceritinib dose that was taken prior to initiating the strong CYP450 3A inhibitor.

Precautions

CONTRAINDICATIONS:

• None

Dialysis

Data not available

Other Comments

Administration Advice:

• This drug should be taken with food.
• Do not consume grapefruit or grapefruit juice because they inhibit CYP450 3A.
• If a dose is missed, make it up unless it is 12 hours or less until the next dose.
• Discontinue in patients unable to tolerate 300 mg a day.

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).

• Select patients for treatment of metastatic NSCLC with this drug based on the presence of ALK positivity in tumor specimens.