ALECENSA

ALECENSA- alectinib hydrochloride capsule
Genentech, Inc.

1 INDICATIONS AND USAGE

ALECENSA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients for the treatment of metastatic NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue or plasma specimens [see Indications and Usage (1) and Clinical Studies (14)]. If ALK rearrangements are not detected in a plasma specimen, test tumor tissue if feasible.

Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics.

2.2 Dosing and Administration

The recommended dose of ALECENSA is 600 mg orally twice daily [see Clinical Pharmacology (12.3)]. Administer ALECENSA until disease progression or unacceptable toxicity.

The recommended dose of ALECENSA in patients with severe hepatic impairment (Child-Pugh C) is 450 mg orally twice daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

ALECENSA should be taken with food. Do not open or dissolve the contents of the capsule. If a dose of ALECENSA is missed or vomiting occurs after taking a dose of ALECENSA, take the next dose at the scheduled time.

2.3 Dose Modifications for Adverse Reactions

The dose reduction schedule for ALECENSA is provided in Table 1.

Table 1: ALECENSA Dose Reduction Schedule
Dose reduction schedule Dose level
Starting dose 600 mg taken orally twice daily
First dose reduction 450 mg taken orally twice daily
Second dose reduction 300 mg taken orally twice daily

Discontinue if patients are unable to tolerate the 300 mg twice daily dose.

Recommendations for dose modifications of ALECENSA in case of adverse reactions are provided in Table 2.

Table 2: ALECENSA Dose Modifications for Adverse Reactions
Criteria * ALECENSA Dose Modification
*
ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase
Heart rate less than 60 beats per minute (bpm)
ALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 1.
ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis Permanently discontinue ALECENSA.
Total bilirubin elevation of greater than 3 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 1.
Any grade treatment-related interstitial lung disease (ILD)/pneumonitis Permanently discontinue ALECENSA.
Grade 3 renal impairment Temporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose.
Grade 4 renal impairment Permanently discontinue ALECENSA.
Symptomatic bradycardia Withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume ALECENSA at reduced dose (see Table 1) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
Bradycardia (life-threatening consequences, urgent intervention indicated) Permanently discontinue ALECENSA if no contributing concomitant medication is identified.If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at reduced dose (see Table 1) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence.
CPK elevation greater than 5 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at same dose.
CPK elevation greater than 10 times ULN or second occurrence of CPK elevation of greater than 5 times ULN Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 1.
Hemolytic Anemia Withhold ALECENSA if hemolytic anemia is suspected.Upon resolution, resume at reduced dose or permanently discontinue.

3 DOSAGE FORMS AND STRENGTHS

150 mg hard capsules, white, with “ALE” printed in black ink on the cap and “150 mg” printed in black ink on the body.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

Elevations of AST greater than 5 times the upper limit of normal (ULN) occurred in 4.6% of patients, and elevations of ALT greater than 5 times the ULN occurred in 5.3% of the 405 patients in Studies NP28761, NP28673 and ALEX who received ALECENSA at a dose of 600 mg BID. Elevations of bilirubin greater than 3 times the ULN occurred in 3.7% of patients. The majority (69% of the patients with hepatic transaminase elevations and 68% of the patients with bilirubin elevations) of these events occurred during the first 3 months of treatment. Six patients discontinued ALECENSA for Grades 3–4 AST and/or ALT elevations, and 4 patients discontinued ALECENSA for Grade 3 bilirubin elevations. Concurrent elevations in ALT or AST greater than or equal to 3 times the ULN and total bilirubin greater than or equal to 2 times the ULN, with normal alkaline phosphatase, occurred in less than 1% of patients treated with ALECENSA across clinical trials. Three patients with Grades 3–4 AST/ALT elevations had drug-induced liver injury (documented by liver biopsy in two cases).

Monitor liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 3 months of treatment, then once a month and as clinically indicated, with more frequent testing in patients who develop transaminase and bilirubin elevations. Based on the severity of the adverse drug reaction, withhold ALECENSA and resume at a reduced dose or permanently discontinue ALECENSA as described in Table 2[see Dosage and Administration (2.3)].

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