alectinib

General

Genetic Implications: Genetic Implications

Pronunciation:
al-ekti-nib


Trade Name(s)

  • Alecensa
  • Alecensaro Canadian Tradename

Ther. Class.
antineoplastics

Pharm. Class.
kinase inhibitors

Indications

Genetic implication Patients with metastatic non-small cell lung cancer (NSCLC) that is positive for anaplastic lymphoma kinase (ALK).

Action

Inhibits tyrosine kinase receptors targeting anaplastic lymphoma kinase (ALK) and RET.

Therapeutic Effect(s):

Decreased spread of NSCLC.

Pharmacokinetics

Absorption: 37% absorbed following oral administration; high-fat, high-calorie meals ↑ absorption.

Distribution: Extensively distributed to tissues.

Protein Binding: 99%.

Metabolism and Excretion: Mostly metabolized by the CYP3A4 isoenzyme to its active metabolite, M4 (also metabolized by CYP3A4). 84% excreted in feces unchanged; minimal excretion in urine.

Half-life: 33 hr (alectinib); 31 hr (M4 active metabolite).

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
POunknown4 hrunknown

Contraindication/Precautions

Contraindicated in:

  • OB:  Pregnancy (may cause fetal harm);
  • Lactation.

Use Cautiously in:

  • Severe renal impairment (CCr <30 mL/min) or end-stage renal disease;
  • Severe hepatic impairment (↓ dose);
  • Rep:  Women of reproductive potential;
  • Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: bradycardia, edema

Derm: photosensitivity, rash

EENT: blurred vision, diplopia

Endo: hyperglycemia

F and E: hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia

GI: HEPATOTOXICITY, constipation, diarrhea, hyperbilirubinemia, nausea, vomiting

GU: ↑ serum creatinine

Hemat: HEMORRHAGE, anemia, lymphopenia, hemolytic anemia

Metabolic: ↑ weight

MS: back pain, ↑ creatine kinase, myalgia

Neuro: fatigue, headache

Resp: INTERSTITIAL LUNG DISEASE, PULMONARY EMBOLISM, cough, dyspnea

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

PO (Adults): 600 mg twice daily.

Hepatic Impairment 
PO (Adults): Severe hepatic impairment (Child-Pugh Class C)– 450 mg twice daily.

Availability

Capsules: 150 mg

Assessment

  • Monitor for signs and symptoms of interstitial lung disease/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:

  • Genetic implication 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 creatine kinase (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.

Implementation

  • PO Administer twice daily with food.  DNC: Swallow capsules whole, do not open or dissolve capsule contents.

Patient/Family Teaching

  • Instruct patient to take alectinib as directed. If a dose is missed or vomiting occurs after taking, omit dose and take next dose at scheduled time. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
  • Advise patient to use sunscreen and lip balm (SPF ≥50) and to wear protective clothing to prevent photosensitivity reaction.
  • Advise patient to notify health care professional if signs and symptoms of liver problems (feeling tired, itchy skin, feeling less hungry than usual, nausea or vomiting, yellowing of skin or whites of eyes, pain on right side of stomach, dark urine, bleeding or bruising more easily than normal), respiratory problems (trouble breathing, shortness of breath, cough, fever), bradycardia (dizziness, lightheadedness, syncope), or myalgia (unexplained muscle pain, tenderness, or weakness) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 1 wk following therapy. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose.

Evaluation/Desired Outcomes

Decreased spread of NSCLC.

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