Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
Alecensa as monotherapy is indicated as adjuvant treatment following complete tumour resection for adult patients with ALK-positive NSCLC at high risk of recurrence (see section 5.1 for selection criteria).
Alecensa as monotherapy is indicated for the first-line treatment of adult patients with ALK-positive advanced NSCLC.
Alecensa as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib.
Treatment with Alecensa should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
A validated ALK assay is necessary for the selection of ALK-positive NSCLC patients. ALK-positive NSCLC status should be established prior to initiation of Alecensa therapy.
The recommended dose of Alecensa is 600 mg (four 150 mg capsules) 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).
Treatment with Alecensa should be continued until disease recurrence, unacceptable toxicity or for 2 years.
Treatment with Alecensa should be continued until disease progression or unacceptable toxicity.
If a planned dose of Alecensa 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 Alecensa, 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 Alecensa. The dose of Alecensa should be reduced in steps of 150 mg twice daily based on tolerability. Alecensa 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 (see sections 4.4 and 4.8):
| CTCAE grade | Alecensa treatment |
|---|---|
| ILD/pneumonitis of any severity grade | Immediately interrupt and permanently discontinue Alecensa 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 Alecensa. |
| 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).
No starting dose adjustment is required in patients with underlying mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Patients with underlying severe hepatic impairment (Child-Pugh C) should receive a starting dose of 450 mg taken twice daily (total dose of 900 mg) (see section 5.2). For all patients with hepatic impairment, appropriate monitoring (e.g. markers of liver function) is advised, see section 4.4.
No dose adjustment is required in patients with mild or moderate renal impairment. Alecensa has not been studied in patients with severe renal impairment. However, since alectinib elimination via the kidney is negligible, no dose adjustment is required in patients with severe renal impairment (see section 5.2).
The limited data on the safety and efficacy of Alecensa in patients aged 65 years and older do not suggest that a dose adjustment is required in elderly patients (see section 5.2). There are no available data on patients over 80 years of age.
The safety and efficacy of Alecensa in children and adolescents below 18 years of age have not been established. No data are available.
Although pharmacokinetic (PK) simulations for Alecensa do not indicate a low exposure in patients with extreme body weight (i.e. >130 kg), alectinib is widely distributed and clinical studies for alectinib enrolled patients within a range of body weights of 36.9−123 kg. There are no available data on patients with body weight above 130 kg.
Alecensa is for oral use. The hard capsules should be swallowed whole, and must not be opened or dissolved. They must be taken with food (see section 5.2).
Patients who experience overdose should be closely supervised and general supportive care instituted. There is no specific antidote for overdose with Alecensa.
5 years.
Blisters:
Store in the original package in order to protect from moisture.
Bottles:
Store in the original package and keep the bottle tightly closed in order to protect from moisture.
Aluminium/aluminium (PA/Alu/PVC/Alu) blisters containing 8 hard capsules.
Pack size: 224 (4 packs of 56) hard capsules.
HDPE bottle with a child-resistant closure and an integrated desiccant.
Pack size: 240 hard capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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