Drug information of alectinib

Mechanism of effect

Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells.

Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Both alectinib and its major active metabolite M4 demonstrate similar in vivo and in vitro activity against multiple mutant forms of ALK.

Pharmacokinetics

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)

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%

Dosage

Adult

600 mg PO BID until disease progression or unacceptable toxicity

Drug contraindications

Hypersensitivity to this drug or components

Side effects

Diarrhea , Headache , edema , nausea , vomiting , asthenia , myalgia , Hypokalemia , Hyperglycemia , Hypocalcemia , Hyperbilirubinemia , Hypophosphatemia , Weight increase , skin rush , tiredness

Interactions

teriflunomide , Remdesivir , lasmiditan

Alerts

• 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 (do 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 (do Dosage Modifications)
• Symptomatic bradycardia may occur; monitor heart rate and blood pressure regularly (do 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 (do Dosage Modifications)
• Based on findings from animal studies and its mechanism of action, alectinib can cause fetal harm when administered to pregnant women

Points of recommendation

Alectinib works best if you take it with food.

Do not crush, chew, dissolve, or open an alectinib capsule. Swallow it whole.

If you vomit shortly after taking an alectinib capsule, do not take another one. Wait until your next scheduled dose and take the regular amount of medicine at that time.

While using alectinib, your heart rate and blood pressure will need to be checked often. You will also need frequent blood tests to check your liver function. Your cancer treatments may be delayed based on the results of these tests.

Store at room temperature away from moisture, heat, and light.

Pregnancy level

Consult a physician before using

Not Assigned Comments

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