ALECENSA

2 DOSAGE AND ADMINISTRATION 600 mg orally twice daily. Administer ALECENSA with food. ( 2.2 ) 2.1 Patient Selection Select patients with resectable tumors for the adjuvant treatment of NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue [see Indications and Usage (1.1) and Clinical Studies (14.1) ]. Select patients for the treatment of metastatic NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue or plasma specimens [see Indications and Usage (1.2) and Clinical Studies (14.2) ] . If ALK rearrangements are not detected in a plasma specimen, test tumor tissue if feasible. Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Dosing and Administration The recommended dosage information for ALECENSA is provided in Table 1 . Table 1: ALECENSA Recommended Dosage and Duration of Treatment Indication Recommended Dosage of ALECENSA Duration Adjuvant treatment of resected NSCLC 600 mg orally twice daily with food [see Clinical Pharmacology (12.3) ] For a total of 2 years or until disease recurrence or unacceptable toxicity Metastatic NSCLC Until disease progression or unacceptable toxicity Swallow capsules whole, do not open or dissolve the contents of the capsule. If a dose of ALECENSA is missed or vomiting occurs after taking a dose of ALECENSA, take the next dose at the scheduled time. 2.3 Recommended Dosage for Hepatic Impairment The recommended dose of ALECENSA in patients with severe hepatic impairment (Child-Pugh C) is 450 mg orally twice daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. 2.4 Dose Modifications for Adverse Reactions The dose reduction schedule for ALECENSA is provided in Table 2 . Table 2: ALECENSA Dose Reduction Schedule Dose Reduction Schedule Dose Level Starting dose 600 mg taken orally twice daily First dose reduction 450 mg taken orally twice daily Second dose reduction 300 mg taken orally twice daily Discontinue if patients are unable to tolerate the 300 mg twice daily dose. Recommendations for dose modifications of ALECENSA in case of adverse reactions are provided in Table 3 . Table 3: ALECENSA Dose Modifications for Adverse Reactions Criteria ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase ALECENSA Dose Modification ALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 2 . ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis Permanently discontinue ALECENSA. Total bilirubin elevation of greater than 3 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 2 . Any grade treatment-related interstitial lung disease (ILD)/pneumonitis Permanently discontinue ALECENSA. Grade 3 renal impairment Temporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose. Grade 4 renal impairment Permanently discontinue ALECENSA. Symptomatic bradycardia Withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume ALECENSA at reduced dose (see Table 2 ) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. Bradycardia Heart rate less than 60 beats per minute (bpm) (life-threatening consequences, urgent intervention indicated) Permanently discontinue ALECENSA if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at reduced dose (see Table 2 ) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence. CPK elevation greater than 5 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at same dose. CPK elevation greater than 10 times ULN or second occurrence of CPK elevation of greater than 5 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 2 . Hemolytic Anemia Withhold ALECENSA if hemolytic anemia is suspected. Upon resolution, resume at reduced dose or permanently discontinue.

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1 INDICATIONS AND USAGE ALECENSA is a kinase inhibitor indicated for: adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive) as detected by an FDA-approved test.