• Monitor for signs and symptoms of ILD/pneumonitis (worsening of respiratory symptoms, dyspnea, cough, fever). Withhold therapy if symptoms occur and permanently discontinue if no other potential causes are identified.
• Monitor heart rate and BP regularly during therapy. If symptomatic bradycardia occurs, withhold therapy until asymptomatic or heart rate ≥60 bpm. If concomitant medication identified as contributing and is discontinued, or its dose adjusted, resume alectinib at previous dose upon recovery to asymptomatic bradycardia or to heart rate ≥60 bpm. If no contributing medication identified, or if contributing medications are not discontinued or dose modified, resume alectinib at reduced dose upon recovery to asymptomatic bradycardia or to heart rate of ≥60 bpm. If life-threatening bradycardia occurs, permanently discontinue alectinib if no contributing medication is identified. If contributing medication is identified and discontinued, or its dose is adjusted, resume alectinib at reduced dose upon recovery to asymptomatic bradycardia or to heart rate of ≥60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue alectinib in case of recurrence.
• Assess for myalgia periodically during therapy.

Lab Test Considerations:

• For patient selection, determine presence of ALK positivity in tumor tissue or plasma specimens using FDA approved test. Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics.
• Dose reduction schedule: 1st dose reduction—450 mg twice daily, 2nd dose reduction 300 mg twice daily. Discontinue if unable to tolerate 300 mg twice daily.
  • Monitor liver function tests every 2 wk during first 3 mo of therapy, and then monthly and as clinically indicated during treatment. If ALT or AST ↑ >5 times upper limit of normal (ULN) with total bilirubin ≤2 times ULN, temporarily withhold until recovery to baseline or ≤3 times ULN, then resume at reduced dose. If ALT or AST ↑ >3 times ULN with total bilirubin ↑>2 times ULN in absence of cholestasis or hemolysis, permanently discontinue alectinib. If total bilirubin ↑ >3 times ULN, temporarily withhold until recovery to baseline or to ≤1.5 times ULN, then resume at reduced dose.
  • Assess CK every 2 wk during 1st mo of therapy and in patients reporting unexplained muscle pain, tenderness, or weakness. If ↑ CK >5 times ULN, temporarily withhold until recovery to baseline or ≤2.5 times ULN, then resume at same dose. If ↑ CK >10 times ULN or 2nd occurrence of ↑ CK >5 times ULN, temporarily withhold until recovery to baseline or ≤2.5 times ULN, then resume at reduced dose.
  • Monitor serum creatinine periodically during therapy. If Grade 3 renal impairment occurs, hold doses until serum creatinine ≤ 1.5 times ULN, then resume at reduced dose. If Grade 4 renal impairment occurs, discontinue alectinib permanently.
  • May cause hyperglycemia, hypocalcemia, hypokalemia, hypophosphatemia, and hyponatremia.
  • May cause anemia and lymphopenia.