Active Ingredient: Alectinib
Alectinib as monotherapy is indicated for the first-line treatment of adult patients with ALK-positive advanced NSCLC.
Alectinib as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 600 milligrams alectinib, 2 times daily to meals.
The recommended dose of alectinib is 600 mg taken twice daily with food (total daily dose of 1200 mg).
Patients with underlying severe hepatic impairment (Child-Pugh C) should receive a starting dose of 450 mg taken twice daily with food (total daily dose of 900 mg).
The limited data on the safety and efficacy of alectinib in patients aged 65 years and older do not suggest that a dose adjustment is required in elderly patients. There are no available data on patients over 80 years of age.
Treatment with alectinib should be continued until disease progression or unacceptable toxicity.
If a planned dose of alectinib is missed, patients can make up that dose unless the next dose is due within 6 hours. Patients should not take two doses at the same time to make up for a missed dose. If vomiting occurs after taking a dose of alectinib, patients should take the next dose at the scheduled time.
Management of adverse events may require dose reduction, temporary interruption, or discontinuation of treatment with alectinib. The dose of alectinib should be reduced in steps of 150 mg twice daily based on tolerability. Alectinib treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose.
Dose modification advice is provided in Tables 1 and 2 below.
Table 1. Dose reduction schedule:
| Dose reduction schedule | Dose level |
|---|---|
| Dose | 600 mg twice daily |
| First dose reduction | 450 mg twice daily |
| Second dose reduction | 300 mg twice daily |
Table 2. Dose modification advice for specified adverse drug reactions:
| CTCAE grade | Alectinib treatment |
|---|---|
| ILD/pneumonitis of any severity grade | Immediately interrupt and permanently discontinue alectinib if no other potential causes of ILD/pneumonitis have been identified. |
| ALT or AST elevation of > 5 times ULN with total bilirubin ≤ 2 times ULN | Temporarily withhold until recovery to baseline or ≤ 3 times ULN, then resume at reduced dose (see Table 1). |
| ALT or AST elevation of > 3 times ULN with total bilirubin elevation > 2 times ULN in the absence of cholestasis or haemolysis | Permanently discontinue alectinib. |
| Bradycardiaa Grade 2 or Grade 3 (symptomatic, may be severe and medically significant, medical intervention indicated) | Temporarily withhold until recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. Evaluate concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive medicinal products. If a contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, resume at previous dose upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. If no contributing concomitant medicinal product is identified, or if contributing concomitant medicinal products are not discontinued or dose modified, resume at reduced dose (see Table 1) upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. |
| Bradycardiaa Grade 4 (life-threatening consequences, urgent intervention indicated) | Permanently discontinue if no contributing concomitant medicinal product is identified. If a contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, resume at reduced dose (see Table 1) upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue in case of recurrence. |
| CPK elevation > 5 times ULN | Temporarily withhold until recovery to baseline or to ≤ 2.5 times ULN, then resume at the same dose. |
| CPK elevation > 10 times ULN or second occurrence of CPK elevation of > 5 times ULN | Temporarily withhold until recovery to baseline or to ≤ 2.5 times ULN, then resume at reduced dose as per Table 1. |
| Haemolytic anaemia with haemoglobin of < 10 g/dL (Grade ≥ 2) | Temporarily withhold until resolution, then resume at reduced dose (see Table 1). |
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; CTCAE = NCI Common Terminology Criteria for Adverse Events; ILD = interstitial lung disease; ULN = upper limit of normal
a Heart rate less than 60 beats per minute (bpm).
It must be taken with food.
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