Dose Modifications

Dose Reductions and Modifications for ALECENSA® (alectinib)

DOSE REDUCTION SCHEDULE 1

Dose Reduction Schedule Dose Level
Starting dose ALECENSA 600 mg taken orally twice daily
First dose reduction ALECENSA 450 mg taken orally twice daily
Second dose reduction ALECENSA 300 mg taken orally twice daily
Discontinue if patients are unable to tolerate the 300 mg twice daily dose.

23% of patients initiating treatment at the recommended dose required at least 1 dose reduction1

6% of patients treated with ALECENSA in clinical trials permanently discontinued treatment due to adverse reactions1

DOSE MODIFICATIONS FOR ADVERSE REACTIONS 1

Criteria ALECENSA Dose Modification
ALT or AST elevation of >5X
ULN with total bilirubin ≤2X ULN
Temporarily withhold until recovery to baseline or to ≤3X ULN, then resume at reduced dose.
See table above for dose reduction schedule.
ALT or AST elevation >3X ULN with total bilirubin elevation >2X ULN in the absence of cholestasis or hemolysis Permanently discontinue ALECENSA.
Total bilirubin elevation of >3X ULN Temporarily withhold until recovery to baseline or to ≤1.5X ULN, then resume at reduced dose.
See table above for dose reduction schedule.
Any Grade treatment-related ILD/pneumonitis Permanently discontinue ALECENSA.
Symptomatic bradycardia Withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm.
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.
If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume ALECENSA at reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm.
See table above for dose reduction schedule.
Bradycardiaa (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 upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence.
See table above for dose reduction schedule.
CPK elevation >5X ULN Temporarily withhold until recovery to baseline or to ≤2.5X ULN, then resume at same dose.
CPK elevation >10X ULN or second occurrence of CPK elevation >5X ULN Temporarily withhold until recovery to baseline or to ≤2.5X ULN, then resume at reduced dose.
See table above for dose reduction schedule.
a Heart rate <60 bpm.

ALT=alanine transaminase; AST=aspartate transaminase; BPM=beats per minute; CPK=creatine phosphokinase; ILD=interstitial lung disease; ULN=upper limit of normal.

ADVERSE REACTIONS

Learn about the adverse reactions associated with ALECENSA in clinical trials.

View Adverse Reactions

DOSING AND ADMINISTRATION GUIDE

Download this guide to learn more about dosing for ALECENSA.

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CONTACT A REPRESENTATIVE

Contact your local Genentech representative for additional information about ALECENSA.

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Indication

ALECENSA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Important Safety Information

Warnings and Precautions

Hepatotoxicity

  • Elevations of AST >5X the upper limit of normal (ULN) occurred in 3.6% of patients, and elevations of ALT >5X the ULN occurred in 4.8% of patients. Elevations of bilirubin >3X the ULN occurred in 2.8% of patients in Studies 1 and 2. The majority (76% 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. Four patients discontinued ALECENSA for Grade 3-4 AST and/or ALT elevations, and three patients discontinued ALECENSA for Grade 3 bilirubin elevations. In Studies 1 and 2, two patients with Grade 3-4 AST/ALT elevations had documented drug-induced liver injury by liver biopsy. Concurrent elevations in ALT or AST ≥3X the ULN and total bilirubin ≥2X the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with ALECENSA across clinical trials
  • 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

Interstitial Lung Disease (ILD)/Pneumonitis

  • Severe ILD (Grade 3) occurred in one (0.4%) of 253 patients exposed to ALECENSA in Studies 1 and 2
  • Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, 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

Bradycardia

  • Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (7.5%) have been reported in patients treated with ALECENSA. Twenty percent of 221 patients treated with ALECENSA for whom serial ECGs were available had heart rates of <50 beats per minute (bpm)
  • Monitor heart rate and blood pressure regularly. Dose modification is not required in cases of asymptomatic bradycardia. In cases of symptomatic bradycardia that is not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If attributable to a concomitant medication, resume ALECENSA at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence. Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified

Severe Myalgia and Creatine Phosphokinase (CPK) Elevation

  • Myalgia or musculoskeletal pain occurred in 29% of patients in Studies 1 and 2. The incidence of Grade 3 myalgia/musculoskeletal pain was 1.2%. Dose modifications for myalgia/musculoskeletal pain were required in 0.8% of patients
  • Elevations of CPK occurred in 43% of 218 patients with CPK laboratory data available in Study 1 and Study 2. The incidence of Grade 3 elevations of CPK was 4.6%. Median time to Grade 3 CPK elevation was 14 days (interquartile range 13-14 days). Dose modifications for elevation of CPK occurred in 5.0% of patients
  • 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

Embryo-Fetal Toxicity

  • Based on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to pregnant women. Administration of ALECENSA to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7X those observed in humans with ALECENSA 600 mg twice daily. Advise pregnant women of the potential risk to a fetus
  • Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week following the final dose

Most Common Adverse Reactions

  • The most common adverse reactions (incidence ≥20%) were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSA

Use in Specific Populations

Pregnancy

  • Based on animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to a pregnant woman. There are no available data on ALECENSA use in pregnant women
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively

Lactation

  • Because of the potential for serious adverse reactions in breast-fed infants from ALECENSA, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after final dose

Females and Males of Reproductive Potential

  • ALECENSA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week after the final dose
  • Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the final dose

Patient Counseling Information

Photosensitivity

  • Inform patients of the signs and symptoms of photosensitivity. Advise patients to avoid prolonged sun exposure while taking ALECENSA and for at least 7 days after discontinuation and to use proper protection from the sun. Advise patients to use a broad spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and lip balm (SPF ≥50) to help protect against potential sunburn

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional Important Safety Information in full Prescribing Information.