alectinib (Rx)

Brand and Other Names:Alecensa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 150mg

Non-small Cell Lung Cancer

Indicated for anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test

600 mg PO BID until disease progression or unacceptable toxicity

See Administration

Dosage Modifications

Dose reduction schedule

  • Starting dose: 600 mg PO BID
  • First dose reduction: 450 mg PO BID
  • Second dose reduction: 300 mg PO BID
  • Discontinue if patients are unable to tolerate 300 mg PO BID

Nephrotoxicity

  • Grade 3: Temporarily withhold until serum creatinine recovers to ≤1.5x ULN, then resume at reduced dose
  • Grade 4: Permanently discontinue

Hepatotoxicity

  • ALT or AST elevation >5x ULN with total bilirubin (TB) ≤2x ULN: Temporarily withhold until recovery to baseline or to ≤3 times ULN, then resume at reduced dose
  • ALT or AST elevation >3x ULN with TB elevation >2x ULN in absence of cholestasis or hemolysis: Permanently discontinue
  • TB elevation >3x ULN: Temporarily withhold until recovery to baseline or to ≤1.5x ULN, then resume at reduced dose

Interstitial lung disease (ILD)/pneumonitis

  • Any grade treatment-related ILD/pneumonitis: Permanently discontinue

Bradycardia

  • Symptomatic bradycardia
    • Withhold until recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm
    • If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume alectinib at previous dose upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm
    • If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume alectinib at reduced dose upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm
  • Life-threatening bradycardia or urgent intervention indicated
    • Permanently discontinue if no contributing concomitant medication is identified
    • If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume alectinib at reduced dose upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm, with frequent monitoring as clinically indicated
    • Permanently discontinue in case of recurrence

Elevated CPK

  • CPK >5x ULN: Temporarily withhold until recovery to baseline or to ≤2.5x ULN, then resume at same dose
  • CPK >10x ULN or second occurrence of >5x ULN: Temporarily withhold until recovery to baseline or to ≤2.5x ULN, then resume at reduced dose

Renal impairment

  • Mild-to-moderate: No dose adjustment required
  • Severe (CrCl <30 mL/min) or ESRD: Not studied

Hepatic impairment

  • Mild (TB ≤ULN and AST >ULN or TB >1-1.5x ULN and any AST): No dose adjustment required
  • Moderate-to-severe: Not studied

Dosing Considerations

Patients should be tested and present ALK-positive tumor specimens prior to treatment

Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

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Adverse Effects

>10% (All Grades)

Anemia (56%)

Increased AST (51%)

Increased alkaline phosphatase (47%)

Increased CPK (43%)

Fatigue (26-41%)

Hyperbilirubinemia (39%)

Hyperglycemia (36%)

Increased ALT (34%)

Constipation (34%)

Hypocalcemia (32%)

Edema (22-30%)

Hypokalemia (29%)

Myalgia (23-29%)

Increased creatinine (28%)

Lymphopenia (22%)

Hypophosphatemia (21%)

Hyponatremia (20%)

Cough (19%)

Rash (15-18%)

Nausea (14-18%)

Headache (17%)

Diarrhea (12-16%)

Dyspnea (16%)

Back pain (12%)

Vomiting (7-12%)

Bradycardia (11%)

Increased weight (11%)

1-10% (All Grades

Vision disorder (10%)

1-10% (Grade 3 or 4)

Increased ALT (4.8%)

Increased CPK (4.6%)

Lymphopenia (4.6%)

Vision disorders (4.6%)

Hypokalemia (4%)

Renal impairment (3.9%)

Dyspnea (3.6%)

Increased AST (3.6%)

Dysgeusia (3.3%)

Hypophosphatemia (2.8%)

Hyperbilirubinemia (2.4%)

Hyperglycemia (2%)

Hyponatremia (2%)

Anemia (2%)

Fatigue (1.2%)

Myalgia (1.2%)

Diarrhea (1.2%)

Increased alkaline phosphatase (1.2%)

<1% (Grade 3 or 4)

Edema (0.7-0.8%)

Headache (0.8%)

Rash (0.4-0.7%)

Dysgeusia (0.7%)

Nausea (0.7%)

Vomiting (0.4%)

Increased weight (0.4%)

Hypocalcemia (0.4%)

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Warnings

Contraindications

None

Cautions

Elevated liver enzymes reported; monitor liver function tests, including ALT, AST, and total bilirubin, q2weeks during the first 2 months of treatment, then periodically during treatment, with more frequent testing in patients who develop transaminase and bilirubin elevations (see Dosage Modifications)

Interstitial lung disease (ILD) and pneumonitis reported; promptly investigate any patient who presents with worsening respiratory symptoms (eg, dyspnea, cough, fever) and immediately withhold treatment in patients diagnosed with ILD/pneumonitis (see Dosage Modifications)

Symptomatic bradycardia may occur; monitor heart rate and blood pressure regularly (see Dosage Modifications)

Severe myalgia and elevated CPK reported; advise patients to report any unexplained muscle pain, tenderness, or weakness; assess CPK levels q2weeks for the first month of treatment and as clinically indicated in patients reporting symptoms (see Dosage Modifications)

Based on findings from animal studies and its mechanism of action, alectinib can cause fetal harm when administered to pregnant women (see Pregnancy)

Renal impairment occurred; incidence of Grade ≥3 renal impairment was 1.7%, of which 0.5% were fatal events (see Dosage Modifications)

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Pregnancy & Lactation

Pregnancy

Based on animal studies and its mechanism of action, can cause fetal harm when administered to a pregnant woman There are no available data on use in humans during pregnancy

Animal data

  • Administration to pregnant rats and rabbits by oral gavage during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7-times those observed in humans treated with alectinib at 600 mg BID

Contraception

  • Females: Use effective contraception during treatment and for 1 week after the final dose
  • Males: Use effective contraception during treatment and for 3 months following the final dose

Lactation

Unknown if distributed in human breast milk

Because of the potential for serious adverse reactions in breastfed infants from alectinib, advise a lactating woman not to breastfeed during treatment and for 1 week after the final dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Tyrosine kinase inhibitor that targets ALK and RET

In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations

The major active metabolite of alectinib, M4, showed similar in vitro potency and activity

Alectinib and M4 demonstrated in vitro and in vivo activity against multiple mutant forms of the ALK enzyme, including some mutations identified in NSCLC tumors in patients who have progressed on crizotinib

Absorption

Absolute bioavailability: 37% (with food)

Peak plasma time: 4 hr (with food)

Peak plasma concentration at steady-state: 665 ng/mL; 246 ng/mL (M4)

AUC: 7430 ng·h/mL; 2810 ng·h/mL (M4)

Steady-state reached: 7 days

Distribution

Protein bound (parent drug and M4 metabolite): >99%

Vd: 4016 L; 10,093 L (M4)

Metabolism

Alectinib is metabolized by CYP3A4 to its major active metabolite M4

M4 is subsequently metabolized by CYP3A4

M4 is a substrate of P-gp

Elimination

Half-life: 33 hr; 31 hr (M4)

Clearance: 81.9 L/hr; 217 L/hr (M4)

Excretion

  • Feces: 84%; 6% (M4)
  • Urine: <0.5%
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Administration

Oral Administration

Take with food

Swallow capsule whole

Do not open or dissolve contents of capsule

If a dose is missed or vomited, take the next dose at the scheduled time (do not take an extra dose)

Storage

Do not store above 30°C (86°F)

Store in the original container to protect from light and moisture

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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