Alecensa Capsule [Genentech, Inc.]: Uses, Dosage & Precautions

ALECENSA is a kinase inhibitor indicated for: adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive) as detected by an FDA-approved test. (1.1)treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test. (1.2)1.1 Adjuvant Treatment of Resected ALK-Positive Non-Small Cell Lung Cancer (NSCLC)ALECENSA is indicated as adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive), as detected by an FDA-approved test [see Dosage & Administration (2.1)]. 1.2 Treatment of Metastatic ALK-Positive NSCLCALECENSA is indicated for the treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test [see Dosage & Administration (2.1)].

None.

The dose reduction schedule for ALECENSA is provided in Table 2.Table 2: ALECENSA Dose Reduction ScheduleDose Reduction ScheduleDose LevelStarting dose600 mg taken orally twice dailyFirst dose reduction450 mg taken orally twice dailySecond dose reduction300 mg taken orally twice dailyDiscontinue 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 3.Table 3: ALECENSA Dose Modifications for Adverse ReactionsCriteriaALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase ALECENSA Dose ModificationALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULNTemporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 2. ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysisPermanently discontinue ALECENSA.Total bilirubin elevation of greater than 3 times ULNTemporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 2.Any grade treatment-related interstitial lung disease (ILD)/pneumonitisPermanently discontinue ALECENSA.Grade 3 renal impairmentTemporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose.Grade 4 renal impairmentPermanently 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 2) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.BradycardiaHeart rate less than 60 beats per minute (bpm) (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 2) 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 ULNTemporarily 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 ULNTemporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 2.Hemolytic AnemiaWithhold ALECENSA if hemolytic anemia is suspected.Upon resolution, resume at reduced dose or permanently discontinue.Severe hypertriglyceridemia (blood triglycerides from 501 to 1,000 mg/dL or from 5.71 to 11.4 mmol/L) OR Life-threatening hypertriglyceridemia (blood triglycerides over 1,000 mg/dL or over 11.4 mmol/L)Temporarily withhold until recovery to at least moderate hypertriglyceridemia (i.e., until blood triglycerides are ≤ 500 mg/dL or ≤ 5.7 mmol/L). Evaluate risk factors for pancreatitis and address those that are treatable before resuming treatment with ALECENSA. If an acute episode of pancreatitis occurs, temporarily withhold until full recovery before resuming treatment with ALECENSA. Resume ALECENSA at the same dose, with regular monitoring of blood triglyceride levels. If hypertriglyceridemia reoccurs, consider dose reduction of ALECENSA.

The following adverse reactions are discussed in greater detail in other sections of the label:Hepatotoxicity [see Warnings and Precautions (5.1)] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)] Renal Impairment [see Warnings and Precautions (5.3)] Bradycardia [see Warnings and Precautions (5.4)] Severe Myalgia and Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.5)] Hemolytic Anemia [see Warnings and Precautions (5.6)] Hypertriglyceridemia Leading to Pancreatitis [see Warnings and Precautions (5.7)] Embryo-Fetal Toxicity [see Warnings and Precautions (5.8)]

Hepatotoxicity: Monitor liver laboratory tests 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. In case of severe ALT, AST, or bilirubin elevations, withhold, then reduce dose, or permanently discontinue ALECENSA. (2.4, 5.1)Interstitial Lung Disease (ILD)/Pneumonitis: Immediately withhold ALECENSA in patients diagnosed with ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis have been identified. (2.4, 5.2)Renal Impairment: Withhold ALECENSA for severe renal impairment, then resume ALECENSA at reduced dose upon recovery or permanently discontinue. (2.4, 5.3)Bradycardia: Monitor heart rate and blood pressure regularly. If symptomatic, withhold ALECENSA then reduce dose, or permanently discontinue. (2.4, 5.4)Severe Myalgia and Creatine Phosphokinase (CPK) Elevation: Assess CPK every 2 weeks during the first month of treatment and in patients reporting unexplained muscle pain, tenderness, or weakness. In case of severe CPK elevations, withhold, then resume or reduce dose. (2.4, 5.5)Hemolytic Anemia: If hemolytic anemia is suspected, withhold ALECENSA. If hemolytic anemia is confirmed, consider resuming at a reduced dose upon resolution or permanently discontinue. (5.6)Severe Hypertriglyceridemia Leading to Pancreatitis: Monitor serum triglycerides before initiation and periodically during treatment. In patients with hypertriglyceridemia, monitor for signs and symptoms of acute pancreatitis. Withhold or permanently discontinue ALECENSA based on severity. (2.4, 5.7)Embryo-Fetal Toxicity: ALECENSA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.8, 8.1, 8.3)5.1 HepatotoxicitySevere hepatotoxicity, including drug-induced liver injury, occurred in patients treated with ALECENSA.In the pooled safety population [see Adverse Reactions (6.1)] of patients who received ALECENSA, hepatotoxicity occurred in 41% of patients and the incidence of Grade ≥ 3 hepatotoxicity was 8%. In the ALINA study, hepatotoxicity occurred in 61% of patients treated with ALECENSA and the incidence of Grade ≥ 3 hepatotoxicity was 4.7%. The majority (72% of 136 patients) of elevated transaminases occurred during the first 3 months of treatment. Treatment discontinuation due to hepatotoxicity occurred in 3.6% of patients who received ALECENSA in the pooled safety population and 1.6% of patients treated in the ALINA study.In the pooled safety population, 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. 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 3 [see Dosage and Administration (2.4)]. 5.2 Interstitial Lung Disease (ILD)/PneumonitisILD/pneumonitis occurred in patients treated with ALECENSA.In the pooled safety population [see Adverse Reactions (6.1)], ILD/pneumonitis occurred in 1.3% of patients treated with ALECENSA with 0.4% of patients experiencing Grade 3 ILD/pneumonitis.Five patients (0.9%) in the pooled safety population discontinued ALECENSA due to ILD/pneumonitis. The median time-to-onset of Grade 3 or higher ILD/pneumonitis was 2.1 months (range: 0.6 months to 3.6 months).Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, and fever). Immediately withhold ALECENSA treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue ALECENSA if no other potential causes of ILD/pneumonitis have been identified [see Dosage and Administration (2.4) and Adverse Reactions (6)].5.3 Renal ImpairmentRenal impairment, including fatal cases, occurred in patients treated with ALECENSA.In the pooled safety population [see Adverse Reactions (6.1)], renal impairment occurred in 12% of patients treated with ALECENSA, including Grade ≥ 3 in 1.7% of patients, of which 0.4% were fatal events. The median time to Grade ≥ 3 renal impairment was 3.7 months (range 0.5 to 31.8 months). Dosage modifications for renal impairment were required in 2.4% of patients.Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity until recovery to less than or equal to 1.5 times ULN, then resume at reduced dose [see Dosage and Administration (2.4)].5.4 Bradycardia Symptomatic bradycardia occurred in patients treated with ALECENSA.In the pooled safety population [see Adverse Reactions (6.1)], bradycardia occurred in 11% of patients treated with ALECENSA. Twenty percent of 521 patients treated with ALECENSA, for whom serial electrocardiograms (ECGs) were available, had post-dose heart rates of less than 50 beats per minute (bpm).Monitor heart rate and blood pressure regularly. For asymptomatic bradycardia dose modification is not required. For symptomatic bradycardia that is not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate ≥ 60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If bradycardia is attributable to a concomitant medication, resume ALECENSA at a reduced dose (see Table 2) upon recovery to asymptomatic bradycardia or to a heart rate of ≥ 60 bpm, with frequent monitoring as clinically indicated.Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified [see Dosage and Administration (2.4)]. Permanently discontinue ALECENSA for recurrence of life-threatening bradycardia.5.5 Severe Myalgia and Creatine Phosphokinase (CPK) Elevation Severe myalgia and creatine phosphokinase (CPK) elevation occurred in patients treated with ALECENSA.In the pooled safety population [see Adverse Reactions (6.1)], myalgia (including muscle- and musculoskeletal-related reactions) occurred in 31% of patients treated with ALECENSA, including Grade ≥ 3 in 0.8% of patients. Dosage modifications for myalgia events were required in 2.1% of patients.In the pooled safety population, of the 491 patients with CPK laboratory data available, elevated CPK occurred in 56% of patients treated with ALECENSA, including 6% Grade ≥ 3. The median time to Grade ≥ 3 CPK elevation was 15 days (interquartile range: 15 to 337 days). Dosage modifications for elevation of CPK occurred in 5% of patients.In the ALINA study, elevated CPK occurred in 77% of 128 patients with CPK laboratory data, including 6% Grade ≥ 3 elevations.Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms. Based on the severity of the CPK elevation, withhold ALECENSA, then resume or reduce dose [see Dosage and Administration (2.4)]. 5.6 Hemolytic AnemiaHemolytic anemia occurred in patients treated with ALECENSA.Hemolytic anemia was initially reported with ALECENSA in the postmarketing setting, including cases associated with a negative direct antiglobulin test (DAT) result. Assessments for the determination of hemolytic anemia were subsequently collected in the ALINA study, where hemolytic anemia was observed in 3.1% of patients treated with ALECENSA. If hemolytic anemia is suspected, withhold ALECENSA and initiate appropriate laboratory testing. If hemolytic anemia is confirmed, consider resuming at a reduced dose upon resolution or permanently discontinue ALECENSA [see Dosage and Administration (2.4)]. 5.7 Severe Hypertriglyceridemia Leading to PancreatitisHypertriglyceridemia, including severe cases associated with life-threatening acute pancreatitis, has been reported in patients treated with ALECENSA in the postmarketing setting.In Study NP28761 [see Adverse Reactions (6.1)], which included systematic monitoring of blood triglycerides, of 98 patients with laboratory data available, hypertriglyceridemia occurred in 57%, including Grade 3 elevations in 7% of patients.Dose modifications due to hypertriglyceridemia occurred in 0.9% of patients, and permanent discontinuation occurred in 0.2% of patients. Monitor blood triglycerides before initiation and periodically during treatment with ALECENSA.In patients with triglyceride levels ≥ 500 mg/dL, withhold ALECENSA and monitor for signs and symptoms of pancreatitis and monitor lipase and amylase periodically until triglyceride levels recover to blood triglycerides ≤ 500 mg/dL or ≤ 5.7 mmol/L. If an acute episode of pancreatitis occurs, temporarily withhold ALECENSA until full recovery. Withhold, then resume at the same or reduced dose or permanently discontinue ALECENSA based on severity [see Dosage and Administration (2.4)]. 5.8 Embryo-Fetal ToxicityBased on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to pregnant women. Oral administration of alectinib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7-fold those observed in humans with alectinib 600 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 5 weeks following the last dose [see Use in Specific Populations (8.1 and 8.3) and Clinical Pharmacology (12.1)].

600 mg orally twice daily. Administer ALECENSA with food. (2.2)2.1 Patient SelectionSelect patients with resectable tumors for the adjuvant treatment of NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue [see Indications and Usage (1.1) and Clinical Studies (14.1)]. 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 (1.2) and Clinical Studies (14.2)]. 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 AdministrationThe recommended dosage information for ALECENSA is provided in Table 1.Table 1: ALECENSA Recommended Dosage and Duration of TreatmentIndicationRecommended Dosage of ALECENSADurationAdjuvant treatment of resected NSCLC600 mg orally twice daily with food [see Clinical Pharmacology (12.3)] For a total of 2 years or until disease recurrence or unacceptable toxicityMetastatic NSCLCUntil disease progression or unacceptable toxicitySwallow capsules whole, 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 Recommended Dosage for Hepatic ImpairmentThe 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)]. 2.4 Dose Modifications for Adverse ReactionsThe dose reduction schedule for ALECENSA is provided in Table 2.Table 2: ALECENSA Dose Reduction ScheduleDose Reduction ScheduleDose LevelStarting dose600 mg taken orally twice dailyFirst dose reduction450 mg taken orally twice dailySecond dose reduction300 mg taken orally twice dailyDiscontinue 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 3.Table 3: ALECENSA Dose Modifications for Adverse ReactionsCriteriaALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase ALECENSA Dose ModificationALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULNTemporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 2. ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysisPermanently discontinue ALECENSA.Total bilirubin elevation of greater than 3 times ULNTemporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 2.Any grade treatment-related interstitial lung disease (ILD)/pneumonitisPermanently discontinue ALECENSA.Grade 3 renal impairmentTemporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose.Grade 4 renal impairmentPermanently 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 2) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.BradycardiaHeart rate less than 60 beats per minute (bpm) (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 2) 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 ULNTemporarily 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 ULNTemporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 2.Hemolytic AnemiaWithhold ALECENSA if hemolytic anemia is suspected.Upon resolution, resume at reduced dose or permanently discontinue.Severe hypertriglyceridemia (blood triglycerides from 501 to 1,000 mg/dL or from 5.71 to 11.4 mmol/L) OR Life-threatening hypertriglyceridemia (blood triglycerides over 1,000 mg/dL or over 11.4 mmol/L)Temporarily withhold until recovery to at least moderate hypertriglyceridemia (i.e., until blood triglycerides are ≤ 500 mg/dL or ≤ 5.7 mmol/L). Evaluate risk factors for pancreatitis and address those that are treatable before resuming treatment with ALECENSA. If an acute episode of pancreatitis occurs, temporarily withhold until full recovery before resuming treatment with ALECENSA. Resume ALECENSA at the same dose, with regular monitoring of blood triglyceride levels. If hypertriglyceridemia reoccurs, consider dose reduction of ALECENSA.

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)].

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

Source: DailyMed, U.S. National Library of Medicine. Additional information compiled from online sources.