Alectinib

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

Alectinib is available under the following different brand names: Alecensa.

Dosages of Alectinib:

Dosage Forms and Strengths

Capsule

• 150 mg

Dosage Considerations – Should be Given as Follows:

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 orally twice daily until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction schedule

• Starting dose: 600 mg orally twice daily
• First dose reduction: 450 mg orally twice daily
• Second dose reduction: 300 mg orally twice daily
• Discontinue if patients are unable to tolerate 300 mg orally twice daily

Nephrotoxicity

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

Hepatotoxicity

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

Interstitial lung disease (ILD)/pneumonitis

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

Bradycardia

• Symptomatic bradycardia
  • o Withhold until recovery to asymptomatic bradycardia or to a heart rate 60 beats per minute (bpm) or greater o 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 or greater o 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 a heart rate 60 bpm or greater
• 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 a heart rate of 60 bpm or greater, with frequent monitoring as clinically indicated
  • Permanently discontinue in case of recurrence

Elevated CPK

• CPK greater than 5 times ULN: Temporarily withhold until recovery to baseline or to up to 2.5 times ULN, then resume at the same dose
• CPK greater than 10 times ULN or second occurrence of greater than 5 times ULN: Temporarily withhold until recovery to baseline or to up to 2.5 times ULN, then resume at reduced dose

Renal impairment

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

Hepatic impairment

• Mild (TB up to ULN and AST greater than ULN or TB greater than 1-1.5 times ULN and any AST): No dose adjustment is required
• Moderate-to-severe: Not studied

Safety and efficacy not established in pediatric patients

Common side effects of alectinib include:

• Anemia
• Increased AST
• Increased alkaline phosphatase
• Increased CPK
• Fatigue
• Hyperbilirubinemia
• High blood sugar (hyperglycemia)
• Increased ALT
• Constipation
• Low blood calcium (hypocalcemia)
• Fluid retention (edema)
• Low blood potassium (hypokalemia)
• Muscle pain
• Increased creatinine
• Low white blood cells (lymphopenia)
• Low blood phosphates (hypophosphatemia)
• Low blood sodium (hyponatremia)
• Cough
• Rash
• Nausea
• Headache
• Diarrhea
• Shortness of breath
• Back pain
• Vomiting
• Slow heart rate
• Weight gain
• Vision disorders
• Renal impairment
• Changes in taste
• Increased alkaline phosphatase
• Vomiting

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Alectinib has no listed severe interactions with other drugs.
• Alectinib has no listed serious interactions with other drugs.
• Alectinib has no listed moderate interactions with other drugs.
• Alectinib has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains alectinib. Do not take Alecensa if you are allergic to alectinib or any ingredients contained in this drug.

Contraindications

• None

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Alectinib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Alectinib?"

Cautions

• Elevated liver enzymes reported; monitor liver function tests, including ALT, AST, and total bilirubin, every 2 weeks during the first 2 months of treatment, then periodically during treatment, with more frequent testing in patients who develop transaminase and bilirubin elevations
• Interstitial lung disease (ILD) and pneumonitis reported; promptly investigate any patient who presents with worsening respiratory symptoms (e.g., shortness of breath, cough, fever) and immediately withhold treatment in patients diagnosed with ILD/pneumonitis
• Symptomatic bradycardia may occur; monitor heart rate and blood pressure regularly
• Severe myalgia and elevated CPK reported; advice patients to report any unexplained muscle pain, tenderness, or weakness; assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms
• Based on findings from animal studies and its mechanism of action, alectinib can cause fetal harm when administered to pregnant women
• Renal impairment occurred; incidence of Grade 3 or greater renal impairment was 1.7%, of which 0.5% were fatal events

Pregnancy and Lactation

• Based on animal studies and its mechanism of action, alectinib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of alectinib in humans during pregnancy.
• Females are advised to use effective contraception during treatment with alectinib and for 1 week after the final dose. Males are advised to use effective contraception during treatment with alectinib and for 3 months following the final dose.
• It is unknown if alectinib is distributed in human breast milk. Because of the potential for serious adverse reactions in breastfed infants from alectinib, lactating women are advised not to breastfeed during treatment and for 1 week after the final dose.