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ALECENSARO is a brand name for Alectinib, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ALECENSARO (alectinib) is indicated: • for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC). • as monotherapy for the treatment of patients with ALK-positive, locally advanced (not…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Geriatrics: No dose adjustment of ALECENSARO is required in patients ≥ 65 years of age.
Renal Impairment:
No dose adjustment is required in patients with mild or moderate renal impairment. ALECENSARO has not been studied in patients with severe renal impairment (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
Hepatic Impairment:
Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg). g. markers of liver function) is advised (see 7 WARNINGS AND PRECAUTIONS, Hepatotoxicity). No dose adjustment is required in patients with underlying mild or moderate hepatic impairment (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
2 Recommended Dose and Dosage Adjustment Standard Dosage The recommended dose of ALECENSARO is 600 mg (four 150 mg capsules) given orally, twice daily with food (total daily dose of 1200 mg).
Duration of treatment Locally advanced or metastatic ALK-positive NSCLC:
It is recommended that patients with locally advanced or metastatic NSCLC are treated with ALECENSARO until disease progression or unmanageable toxicity.
Adjuvant treatment of resected ALK-positive NSCLC:
It is recommended that patients with resected NSCLC are treated with ALECENSARO as adjuvant therapy until disease recurrence, unacceptable toxicity or for 2 years. Dosage Adjustment Management of adverse events may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSARO.
The dose of ALECENSARO should be reduced in steps of 150 mg twice daily based on tolerability. ALECENSARO treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose. Table 1 below presents general dose modification recommendation for ALECENSARO.
Table 1 Dose Reduction Schedule Dose reduction schedule Dose level Starting dose 600 mg twice daily First dose reduction 450 mg twice daily Second dose reduction 300 mg twice daily Recommendations for dose modifications of ALECENSARO in case of adverse reactions are provided in Table 2.
, Clinical Trial Adverse Drug Reactions). 3 Reconstitution Not applicable. 4 Administration ALECENSARO is for oral use. The hard capsules should be swallowed whole, and must not be opened or dissolved. They must be taken with food. 5 Missed Dose If a dose of ALECENSARO is missed, take the next dose at the next scheduled time.
Vomiting If vomiting occurs after taking a dose of ALECENSARO, patients should take the next dose at the scheduled time. 5 OVERDOSAGE There is no experience with overdosage across clinical trials. Patients who experience overdose should be closely supervised and supportive care instituted.
There is no specific antidote for overdose with ALECENSARO. For management of a suspected drug overdose, contact your regional poison control centre. ALECENSARO® (alectinib) Page 9 of 52 Protected B / Protégé B 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table – Dosage Forms, Strengths, Composition and Packaging Non-medicinal ingredients (alphabetical order) of capsule shell include: carnauba wax, carrageenan, corn starch, hypromellose, potassium chloride, titanium dioxide, and trace of printing ink.
Packaging ALECENSARO is supplied as hard capsules, white, with “ALE” printed in black ink on the cap and “150 mg” printed in black ink on the body. ALECENSARO is available in bottles of 240 capsules. 7 WARNINGS AND PRECAUTIONS Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
General Patients treated with ALECENSARO must have a documented ALK-positive status based on a validated ALK assay. Assessment for ALK-positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilized.
Improper assay performance can lead to unreliable test results. Carcinogenesis and Mutagenesis No carcinogenicity studies have been conducted with ALECENSARO. In vitro, alectinib is aneugenic, but not mutagenic or clastogenic (see 16 NON-CLINICAL TOXICOLOGY).
, Cardiovascular) • Gastrointestinal perforation (see 7 WARNINGS AND PRECAUTIONS, Gastrointestinal) • Interstitial lung disease (see 7 WARNINGS AND PRECAUTIONS, Respiratory) • Hepatotoxicity, including drug-induced liver injury (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic) • ALECENSARO has not been studied in patients with severe renal impairment (see 7 WARNINGS AND PRECAUTIONS, Special Populations) • ALECENSARO should be prescribed and supervised by a qualified physician experienced in the ALECENSARO® (alectinib) Page 6 of 52 Protected B / Protégé B use of anticancer agents.
1 Dosing Considerations Geriatrics: No dose adjustment of ALECENSARO is required in patients ≥ 65 years of age.
Renal Impairment:
No dose adjustment is required in patients with mild or moderate renal impairment. ALECENSARO has not been studied in patients with severe renal impairment (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
Hepatic Impairment:
Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg). g. markers of liver function) is advised (see 7 WARNINGS AND PRECAUTIONS, Hepatotoxicity). No dose adjustment is required in patients with underlying mild or moderate hepatic impairment (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
2 Recommended Dose and Dosage Adjustment Standard Dosage The recommended dose of ALECENSARO is 600 mg (four 150 mg capsules) given orally, twice daily with food (total daily dose of 1200 mg).
Duration of treatment Locally advanced or metastatic ALK-positive NSCLC:
It is recommended that patients with locally advanced or metastatic NSCLC are treated with ALECENSARO until disease progression or unmanageable toxicity.
• Patients with known hypersensitivity to alectinib or any of the excipients. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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ALECENSARO® (alectinib) Page 7 of 52 Protected B / Protégé B Table 2 Dose Modifications for Specific Adverse Drug Reactions Criteria ALECENSARO Dosing Gastrointestinal perforation Permanently discontinue ALECENSARO. Interstitial lung disease (ILD)/pneumonitis of any severity grade Immediately interrupt ALECENSARO treatment and permanently discontinue if no other potential causes of ILD/pneumonitis have been identified.
Renal impairment Grade 3 Temporarily withhold until serum creatinine recovers to baseline or Grade 1, then resume at reduced dose. Renal impairment Grade 4 Permanently discontinue ALECENSARO. 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 hemolysis Permanently discontinue ALECENSARO. 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 beats per minute (bpm).
Evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSARO at previous dose upon recovery to Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm.
If no contributing concomitant medication is identified, or if contributing concomitant medications 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 ALECENSARO treatment if no contributing concomitant medication is identified. If contributing concomitant medication 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. 5 times ULN, then resume at same dose. 5 times ULN, then resume at reduced dose as per Table 1. ALECENSARO® (alectinib) Page 8 of 52 Protected B / Protégé B Criteria ALECENSARO Dosing Hemolytic anemia with hemoglobin of < 10 g/dL (Grade ≥ 2) Temporarily withhold until resolution, then resume at reduced dose (see Table 1) or permanently discontinue.
ALT = alanine transaminase; AST = aspartate transaminase, ULN = upper limit of normal a Heart rate less than 60 beats per minute (bpm).
Special Populations:
Renal Impairment: No dose adjustment is required in patients with mild or moderate renal impairment (CrCl 30 to less than 90 mL/min). ALECENSARO has not been studied in patients with severe renal impairment (CrCl less than 30 mL/min) (see 10 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
Hepatic Impairment:
No dose adjustment is required in patients with underlying mild or moderate hepatic impairment. Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg) (see 4 DOSAGE AND ADMINISTRATION, Recommended Dose and Dose Adjustment).
g. markers of liver […]
Cardiovascular Bradycardia Symptomatic bradycardia can occur with ALECENSARO. In patients with locally advanced or metastatic NSCLC, cases of bradycardia and sinus bradycardia have been reported in patients treated with ALECENSARO. Two patients experienced bradycardia/sinus bradycardia which led to dose reduction.
2 Pharmacodynamics). In patients with resected NSCLC, cases of bradycardia and sinus bradycardia have also been reported in patients treated with ALECENSARO as adjuvant therapy. 2 Pharmacodynamics). ALECENSARO treatment resulted in a decrease in heart rate (HR) of approximately 11 to 13 beats per minute (bpm) at Week 2 in the Phase I/II studies with crizotinib pre-treated patients, which was maintained throughout the treatment period.
The decrease in HR was reversible upon discontinuation. In the Phase III BO28984 (ALEX) study with treatment-naïve patients, the median decrease in HR reached a plateau of approximately 17 bpm at Week 4. A decrease in median HR values was also observed in the Phase III BO40336 (ALINA) study.
In the alectinib arm, a post-baseline decrease in Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Capsule/150 mg Carboxymethylcellulose calcium, Hydroxypropylcellulose, Lactose monohydrate, Magnesium stearate, Sodium lauryl sulfate ALECENSARO® (alectinib) Page 10 of 52 Protected B / Protégé B median heart rate values was observed, with values decreasing from a median of 73 bpm at baseline, plateauing between Week 3 (median of 66 bpm) and Week 24 (median of 62 bpm; heart rate not assessed between these two visits), to 60 bpm at Week 60.
Twenty percent of patients in the Phase I/II studies, as well as 15% of patients in the Phase III BO28984 (ALEX) and Phase III BO40336 (ALINA) studies, for whom serial electrocardiograms (ECGs) were available, had post-dose HRs below 50 bpm.
The reduction on HR appears to be correlated to alectinib plasma concentration. Patients presenting with baseline symptomatic bradycardia were not studied across clinical trials. Co-administration of medicines that lower HR should be avoided to the extent possible (see
Adjuvant treatment of resected ALK-positive NSCLC:
It is recommended that patients with resected NSCLC are treated with ALECENSARO as adjuvant therapy until disease recurrence, unacceptable toxicity or for 2 years. Dosage Adjustment Management of adverse events may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSARO.
The dose of ALECENSARO should be reduced in steps of 150 mg twice daily based on tolerability. ALECENSARO treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose. Table 1 below presents general dose modification recommendation for ALECENSARO.
Table 1 Dose Reduction Schedule Dose reduction schedule Dose level Starting dose 600 mg twice daily First dose reduction 450 mg twice daily Second dose reduction 300 mg twice daily Recommendations for dose modifications of ALECENSARO in case of adverse reactions are provided in Table 2.
ALECENSARO® (alectinib) Page 7 of 52 Protected B / Protégé B Table 2 Dose Modifications for Specific Adverse Drug Reactions Criteria ALECENSARO Dosing Gastrointestinal perforation Permanently discontinue ALECENSARO. Interstitial lung disease (ILD)/pneumonitis of any severity grade Immediately interrupt ALECENSARO treatment and permanently discontinue if no other potential causes of ILD/pneumonitis have been identified.
Renal impairment Grade 3 Temporarily withhold until serum creatinine recovers to baseline or Grade 1, then resume at reduced dose. Renal impairment Grade 4 Permanently discontinue ALECENSARO. 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 hemolysis Permanently discontinue ALECENSARO. 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 beats per minute (bpm).
Evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSARO at previous dose upon recovery to Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm.
If no contributing concomitant medication is identified, or if contributing concomitant medications 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 ALECENSARO treatment if no contributing concomitant medication is identified. If contributing concomitant medication 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. 5 times ULN, then resume at same dose. 5 times ULN, then resume at reduced dose as per Table 1. ALECENSARO® (alectinib) Page 8 of 52 Protected B / Protégé B Criteria ALECENSARO Dosing Hemolytic anemia with hemoglobin of < 10 g/dL (Grade ≥ 2) Temporarily withhold until resolution, then resume at reduced dose (see Table 1) or permanently discontinue.
ALT = alanine transaminase; AST = aspartate transaminase, ULN = upper limit of normal a Heart rate less than 60 beats per minute (bpm).
Special Populations:
Renal Impairment: No dose adjustment is required in patients with mild or moderate renal impairment (CrCl 30 […]