NDC 50242-130 Alecensa

Alectinib Hydrochloride

NDC Product Code 50242-130

NDC 50242-130-01

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 240 CAPSULE in 1 BOTTLE, PLASTIC

NDC 50242-130-86

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 240 CAPSULE in 1 BOTTLE, PLASTIC

NDC Product Information

Alecensa with NDC 50242-130 is a a human prescription drug product labeled by Genentech, Inc.. The generic name of Alecensa is alectinib hydrochloride. The product's dosage form is capsule and is administered via oral form.

Dosage Form: Capsule - A solid oral dosage form consisting of a shell and a filling. The shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band. Capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Alecensa Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • HYDROXYPROPYL CELLULOSE (1200000 MW) (UNII: RFW2ET671P)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • CARBOXYMETHYLCELLULOSE CALCIUM (UNII: UTY7PDF93L)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CARRAGEENAN (UNII: 5C69YCD2YJ)
  • POTASSIUM CHLORIDE (UNII: 660YQ98I10)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • CARNAUBA WAX (UNII: R12CBM0EIZ)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • FD&C BLUE NO. 2 (UNII: L06K8R7DQK)
  • SHELLAC (UNII: 46N107B71O)
  • GLYCERYL OLEATE (UNII: 4PC054V79P)

Administration Route(s)

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The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Kinase Inhibitor - [EPC] (Established Pharmacologic Class)
  • Kinase Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Genentech, Inc.
Labeler Code: 50242
FDA Application Number: NDA208434 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 12-11-2015 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Alectinib

Alectinib is pronounced as (al ek' ti nib)

Why is alectinib medication prescribed?
Alectinib is used to treat a certain type of non-small-cell lung cancer (NSCLC) that has spread to other parts of the body in people who were not treated successfully wit...
[Read More]

* Please review the disclaimer below.

Alecensa Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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.

2.1 Patient Selection

Select patients for the treatment of metastatic NSCLC with ALECENSA based on the presence of ALK positivity in tumor specimens [see Indications and Usage (1) and Clinical Studies (14)].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 with food [see Clinical Pharmacology (12.3)]. Administer ALECENSA until disease progression or unacceptable toxicity.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 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 2.Table 2: ALECENSA Dose Modifications for Adverse ReactionsCriteriaALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinaseALECENSA 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 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 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 1.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 1) 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 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 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 1.

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.

5.1 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)].

5.2 Interstitial Lung Disease (Ild)/Pneumonitis

ILD/pneumonitis occurred in three (0.7%) patients treated with ALECENSA in Studies NP28761, NP28673 and ALEX. One (0.2%) of these events was severe (Grade 3). 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 (2.3) and Adverse Reactions (6)].

5.3 Renal Impairment

Renal impairment occurred in 8% of patients in Studies NP28761, NP28673, and ALEX. The incidence of Grade ≥ 3 renal impairment was 1.7%, of which 0.5% were fatal events. Dose modifications for renal impairment were required in 3.2% of patients. Median time to Grade ≥ 3 renal impairment was 3.7 months (range 0.5 to 14.7 months). 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 (2.3)].

5.4 Bradycardia

Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (8.6%) have been reported in patients treated with ALECENSA in Studies NP28761, NP28673 and ALEX. Eighteen percent of 365 patients treated with ALECENSA for whom serial ECGs were available had heart rates of less than 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 or above 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 (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. Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified [see Dosage and Administration (2.3)].

5.5 Severe Myalgia And Creatine Phosphokinase (Cpk) Elevation

Myalgia or musculoskeletal pain occurred in 26% of patients in Studies NP28761, NP28673 and ALEX. The incidence of Grade 3 myalgia/musculoskeletal pain was 0.7%. Dose modifications for myalgia/musculoskeletal pain were required in 0.5% of patients. Elevations of CPK occurred in 41% of 347 patients with CPK laboratory data available in Studies NP28761, NP28673 and ALEX. The incidence of Grade 3 elevations of CPK was 4.0%. Median time to Grade 3 CPK elevation was 14 days (interquartile range 13-28 days). Dose modifications for elevation of CPK occurred in 3.2 % 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 [see Dosage and Administration (2.3)].

5.6 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 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 times those observed in humans with alectinib 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 [see Use in Specific Populations (8.1 and 8.3) and Clinical Pharmacology (12.1)].

6 Adverse Reactions

  • 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)]Embryo-Fetal Toxicity [see Warnings and Precautions (5.6)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Other

Previously Untreated ALK-Positive Metastatic NSCLC The safety of ALECENSA was evaluated in 152 patients with ALK-positive NSCLC in the ALEX study. The median duration of exposure to ALECENSA was 17.9 months. Patient characteristics of the ALEX study population (n=303) were: median age 56 years, age less than 65 (77%), female (56%), Caucasian (50%), Asian (46%), adenocarcinoma histology (92%), never smoker (63%), and ECOG PS 0 or 1 (93%). Serious adverse reactions occurred in 28% of patients treated with ALECENSA; serious adverse reactions reported in 2% or more of patients treated with ALECENSA were pneumonia (4.6%), and renal impairment (3.9%). Grade ≥ 3 adverse events were reported for 41% of patients in the ALECENSA arm. Fatal adverse reactions occurred in 3.3% of patients treated with ALECENSA; these were renal impairment (2 patients), sudden death, cardiac arrest, and pneumonia (1 patient each). Permanent discontinuation of ALECENSA for adverse reactions occurred in 11% of patients. Adverse drug reactions that led to discontinuation of ALECENSA in 1% or more of patients were renal impairment (2.0%), hyperbilirubinemia (1.3%), increased ALT (1.3%), and increased AST (1.3%). Dose reductions and drug interruption due to adverse reactions occurred in 16% and 19% of patients, respectively, in the ALECENSA arm. The most frequent adverse reactions that led to dose modifications in the ALECENSA arm were hyperbilirubinemia (6%), increased AST (5%), increased ALT (4.6%), and pneumonia (3.3%). Tables 3 and 4 summarize the common adverse reactions and laboratory abnormalities observed in ALEX.Table 3: Adverse Drug Reactions (>10% for all NCI CTCAE Grades or ≥2% for Grades 3-4) in Patients Treated with ALECENSA in ALEXAlecensaN = 152CrizotinibN= 151Adverse ReactionAll Grades (%)Grades 3-4 (%)All Grades (%)Grades 3-4 (%)NCI CTCAE= National Cancer Institute Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities; SOC = System Organ Class.Gastrointestinal  Constipation340330  Nausea140.7483.3  Diarrhea120452.0  Vomiting70383.3General  FatigueIncludes fatigue and asthenia.261.3230.7  EdemaIncludes peripheral edema, edema, eyelid edema, localized edema, and face edema.220.7340.7Musculoskeletal  MyalgiaIncludes myalgia and musculoskeletal pain.2304.00Skin  RashIncludes rash, rash maculo-papular, dermatitis acneiform, erythema, generalized rash, rash macular, rash papular, exfoliative rash, and pruritic rash.150.7130Nervous system  DysgeusiaIncludes dysgeusia and hypogeusia.3.30.7190Eye  Vision disordersIncludes blurred vision, visual impairment, vitreous floaters, reduced visual acuity, and diplopia.4.60230Cardiac  BradycardiaIncludes reported cases of bradycardia and sinus bradycardia but is not based on serial ECG assessment.110150Renal  Renal impairmentIncludes increased blood creatinine, creatinine renal clearance decreased, glomerular filtration rate decreased, and acute kidney injury.12 3.9Includes two Grade 5 events.00The following additional clinically significant adverse drug reactions were observed in patients treated with ALECENSA: weight gain (9.9%), photosensitivity reaction (5.3%), stomatitis (3.3%), interstitial lung disease (1.3%), and drug-induced liver injury (1.3%).Table 4: Treatment-Emergent Worsening in Laboratory Values Occurring in > 10% of Patients in ALEXParameterALECENSAN= 152CrizotinibN=151All Grades (%)Grades 3–4 (%)All Grades (%)Grades 3–4 (%)Note: Based on National Cancer Institute Common Terminology Criteria for Adverse Events v4.03.Excludes patients with no post-baseline lab assessments.Chemistry  Hyperbilirubinemian=147 for alectinib (with baseline values missing for 1 of these patients), n=148 for crizotinib.5454.70  Increased ASTn=147 for alectinib (with baseline valuesmissing for 2 of these patients), n=148 for crizotinib.5065611  Increased alkaline phosphatasen=147 for alectinib, n=148 for crizotinib.500440  Increased ALT4066216  Increased creatinine,Only patients with creatinine increases based on ULN definition.384.1230.7  Increased CPKn=143 for alectinib (with baseline values missing for 14 of these patients), n=143 for crizotinib (with baseline values missing for 13 of these patients). 372.8521.4  Hypocalcemia290611.4  Hyperglycemian=134 for alectinib (with baseline values missing for 18 of these patients), n=131 for crizotinib (with baseline values missing for 8 of these patients).222.2192.3  Hyponatremian=147 for alectinib, n=148 for crizotinib (with baseline values missing for 1 of these patients).186204.1  Hypokalemia172120.7  Hypoalbuminemian=146 for alectinib (with baseline values missing for 1 of these patients), n=148 for crizotinib (with baseline values missing for 1 of these patients).140573.4  Hyperkalemia121.4161.4  Hypophosphatemian=145 for alectinib (with baseline values missing for 2 of these patients), n=148 for crizotinib (with baseline values missing for 4 of these patients).91.4252.7  Increased gamma glutamyl transferasen=143 for alectinib (with baseline values missing for 4 of these patients), n=148 (with baseline values missing for 5 of these patients).70.7394.1Hematology  Anemia627360.7  Lymphopenia141.4344.1  Neutropenia140367

ALK-Positive Metastatic NSCLC Previously Treated with Crizotinib The safety of ALECENSA was evaluated in 253 patients with ALK-positive non-small cell lung cancer (NSCLC) treated with ALECENSA in two clinical trials, Studies NP28761 and NP28673. The median duration of exposure to ALECENSA was 9.3 months. One hundred sixty-nine patients (67%) were exposed to ALECENSA for more than 6 months, and 100 patients (40%) for more than one year. The population characteristics were: median age 53 years, age less than 65 (86%), female (55%), White (74%), Asian (18%), NSCLC adenocarcinoma histology (96%), never or former smoker (98%), ECOG Performance Status (PS) 0 or 1 (91%), and prior chemotherapy treatment (78%). Serious adverse reactions occurred in 19% of patients; the most frequently reported serious adverse reactions were pulmonary embolism (1.2%), dyspnea (1.2%), and hyperbilirubinemia (1.2%). Fatal adverse reactions occurred in 2.8% of patients and included hemorrhage (0.8%), intestinal perforation (0.4%), dyspnea (0.4%), pulmonary embolism (0.4%), and endocarditis (0.4%). Permanent discontinuation of ALECENSA for adverse reactions occurred in 6% of patients. The most frequent adverse reactions that led to permanent discontinuation were hyperbilirubinemia (1.6%), increased ALT levels (1.6%), and increased AST levels (1.2%). Overall, 23% of patients initiating treatment at the recommended dose required at least one dose reduction. The median time to first dose reduction was 48 days. The most frequent adverse reactions that led to dose reductions or interruptions were elevations in bilirubin (6%), CPK (4.3%), ALT (4.0%), and AST (2.8%), and vomiting (2.8%). Tables 5 and 6 summarize the common adverse reactions and laboratory abnormalities observed in Studies NP28761 and NP28673.Table 5: Adverse Reactions in ≥ 10% (All Grades) or ≥ 2% (Grade 3–4) of Patients in Studies NP28761 and NP28673Adverse ReactionsALECENSA N=253All Grades (%)Grades 3–4 (%)Per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0FatigueIncludes fatigue and asthenia.411.2Constipation340EdemaIncludes peripheral edema, edema, generalized edema, eyelid edema, and periorbital edema.300.8MyalgiaIncludes myalgia and musculoskeletal pain.291.2Cough190RashIncludes rash, maculopapular rash, acneiform dermatitis, erythema, generalized rash, papular rash, pruritic rash, and macular rash. 180.4Nausea180Headache170.8Diarrhea161.2Dyspnea163.6Includes one Grade 5 event.Back pain120Vomiting120.4Increased weight110.4Vision disorderIncludes blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia.100An additional clinically significant adverse drug reaction was photosensitivity, which occurred in 9.9% of patients exposed to ALECENSA in Studies NP28761 and NP28673. Patients were advised to avoid sun exposure and to use broad-spectrum sunscreen. The incidence of Grade 2 photosensitivity was 0.4%; the remaining events were Grade 1 in severity. Table 6: Treatment-Emergent Worsening in Laboratory Values Occurring in > 20% of Patients in Studies NP28761 and NP28673ParameterALECENSA N=250All Grades (%)Grades 3–4 (%)Per CTCAE version 4.0Chemistry  Increased AST513.6  Increased Alkaline Phosphatase471.2  Increased CPKn=218 for CPK (with baseline values missing for 91 of these patients).434.6  Hyperbilirubinemia392.4  Hyperglycemian=152 for fasting blood glucose (with baseline values missing for 5 of these patients).362.0  Increased ALT 344.8  Hypocalcemia 320.4  Hypokalemia294.0  Increased CreatinineOnly patients with creatinine increases based on ULN definition.280  Hypophosphatemia 212.8  Hyponatremia 202.0Hematology  Anemia562.0  Lymphopenian=217 for lymphocytes (with baseline values missing for 5 of these patients).224.6

Risk SummaryBased on animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on ALECENSA use in pregnant women. Administration of alectinib to pregnant rats and rabbits by oral gavage during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7 times those observed in humans treated with alectinib at 600 mg twice daily [see Data]. Advise pregnant women of the potential risk to a fetus.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.

Data

Animal DataIn a preliminary rabbit embryo-fetal study, administration of alectinib by oral gavage during the period of organogenesis resulted in abortion or complete embryo-fetal mortality at a maternally toxic dose of 27 mg/kg/day (approximately 2.9-fold the estimated area under the curve (AUC0-24h,ss) in humans treated with alectinib 600 mg BID) in three of six pregnant rabbits. The remaining three pregnant rabbits in this group had few live fetuses, decreased fetal and placental weights, and retroesophageal subclavian artery. In a rat preliminary embryo-fetal development study, administration of alectinib during organogenesis resulted in complete litter loss in all pregnant rats at 27 mg/kg/day (approximately 4.5-fold the estimated AUC0-24h,ss in humans treated with alectinib 600 mg BID). Doses greater than or equal to 9 mg/kg/day (approximately 2.7-fold the estimated human AUC0-24h,ss in humans treated with alectinib 600 mg BID), resulted in maternal toxicity as well as developmental toxicities including decreased fetal weight, dilated ureter, thymic cord, small ventricle and thin ventricle wall, and reduced number of sacral and caudal vertebrae.

Risk SummaryThere are no data on the presence of alectinib or its metabolites in human milk, the effects of alectinib on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from alectinib, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after the final dose.

Contraception

FemalesALECENSA 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 [see Use in Specific Populations (8.1)].

MalesBased 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 [see Nonclinical Toxicology (13.1)].

Animal DataJuvenile animal studies have not been conducted using alectinib. In general toxicology studies, treatment of rats with doses of alectinib resulting in exposures greater than or equal to approximately 4.5 times those in humans treated with alectinib at 600 mg twice daily resulted in changes in the growing teeth and bones. Findings in teeth included discoloration and changes in tooth size along with histopathological disarrangement of the ameloblast and odontoblast layers. There were also decreases in the trabecular bone and increased osteoclast activity in the femur and sternum.

Cardiac ElectrophysiologyThe ability of alectinib to prolong the QT interval was assessed in 221 patients administered ALECENSA 600 mg twice daily in clinical studies. ALECENSA did not prolong the QTc (QT corrected for heart rate) interval to any clinically relevant extent. One patient had a maximum post-baseline QTcF value of greater than 500 msec, and one patient had a maximum QTcF change from baseline of greater than 60 msec.

AbsorptionAlectinib reached maximal concentrations at 4 hours following administration of ALECENSA 600 mg twice daily under fed conditions in patients with ALK-positive NSCLC. The absolute bioavailability of alectinib was 37% (90% CI: 34%, 40%) under fed conditions.A high-fat, high-calorie meal increased the combined exposure (AUC0-inf) of alectinib plus M4 by 3.1-fold (90% CI: 2.7, 3.6) following oral administration of a single 600 mg dose of ALECENSA.

DistributionThe apparent volume of distribution is 4,016 L for alectinib and 10,093 L for M4.Alectinib and M4 are bound to human plasma proteins greater than 99%, independent of drug concentration. Alectinib concentrations in the cerebrospinal fluid in patients with ALK-positive NSCLC approximate estimated alectinib free concentrations in the plasma.In vitro studies suggest that alectinib is not a substrate of P-glycoprotein (P-gp), but M4 is a substrate of P-gp. Alectinib and M4 are not substrates of breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP) 1B1, or OATP1B3.

EliminationThe apparent clearance (CL/F) is 81.9 L/hour for alectinib and 217 L/hour for M4. The geometric mean elimination half-life is 33 hours for alectinib and 31 hours for M4 in patients with ALK-positive NSCLC.

MetabolismAlectinib is metabolized by CYP3A4 to its major active metabolite M4. The geometric mean metabolite/parent exposure ratio at steady-state is 0.40. M4 is subsequently metabolized by CYP3A4. Alectinib and M4 were the main circulating moieties in plasma, constituting 76% of the total radioactivity.

ExcretionNinety-eight percent of the radioactivity was excreted in feces following oral administration of a single radiolabeled dose of alectinib under fed conditions. Eighty-four percent of the dose was excreted in the feces as unchanged alectinib, and 6% of the dose was excreted as M4. Excretion of radioactivity in urine was less than 0.5% of administered radiolabeled dose of alectinib.

Specific PopulationsAge, body weight, mild hepatic impairment, mild to moderate renal impairment (creatinine clearance 30 to 89 mL/min), race (White, Asian, and Other), and sex had no clinically meaningful effect on the systemic exposure of alectinib and M4. The pharmacokinetics of alectinib have not been studied in patients with severe renal impairment, end-stage renal disease or moderate to severe hepatic impairment [see Use in Specific Populations (8.6, 8.7)].

Drug Interactions

Effect of Other Drugs on Alectinib No clinically meaningful effect on the combined exposure of alectinib plus M4 was observed in clinical studies following co-administration of ALECENSA with a strong CYP3A inhibitor (posaconazole), a strong CYP3A inducer (rifampin), or an acid-reducing agent (esomeprazole).

Effect of Alectinib on Other DrugsNo clinically meaningful effect on the exposure of midazolam (sensitive CYP3A substrate) or repaglinide (sensitive CYP2C8 substrate) is expected following co-administration with ALECENSA. In vitro studies suggest that alectinib and M4 do not inhibit CYP1A2, 2B6, 2C9, 2C19 or 2D6.In vitro studies suggest that alectinib and M4 inhibit P-gp and BCRP. Alectinib did not inhibit OATP1B1, OATP1B3, OAT1, OAT3, or OCT2 transport activity in vitro.

Previously Untreated ALK-Positive Metastatic NSCLC The efficacy of ALECENSA for the treatment of patients with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease was established in an open-label, randomized, active-controlled, multicenter study (ALEX: NCT02075840). Patients were required to have an ECOG performance status of 0-2 and ALK-positive NSCLC as identified by the VENTANA ALK (D5F3) CDx assay. Neurologically stable patients with treated or untreated central nervous system (CNS) metastases, including leptomeningeal metastases, were eligible; patients with neurologic signs and symptoms due to CNS metastases were required to have completed whole brain radiation or gamma knife irradiation at least 14 days prior to enrollment and be clinically stable. Patients with a baseline QTc > 470 ms were ineligible.Patients were randomized 1:1 to receive ALECENSA 600 mg orally twice daily or crizotinib 250 mg orally twice daily. Randomization was stratified by ECOG performance status (0/1 vs. 2), race (Asian vs. non-Asian), and the presence or absence of CNS metastases at baseline. Treatment on both arms was continued until disease progression or unacceptable toxicity. The major efficacy outcome measure was progression-free survival (PFS) as determined by investigator assessment according to RECIST v1.1. Additional efficacy outcome measures were PFS as determined by independent review committee (IRC), time to CNS progression by IRC based on RECIST v1.1, objective response rate (ORR) and duration of response (DOR), and overall survival (OS). Additional exploratory outcome measures were CNS objective response rate (CNS-ORR) and CNS duration of response (CNS-DOR) by IRC in patients with CNS metastases at baseline.A total of 303 patients were randomized to ALECENSA (n=152) or crizotinib (n=151). The demographic characteristics of the study population were 56% female, median age 56 years (range: 18 to 91 years), 50% White, 46% Asian, 1% Black, and 3% other races. The majority of patients had adenocarcinoma (92%) and never smoked (63%). CNS metastases were present in 40% (n=122) of patients: of these, 43 patients had measurable CNS lesions as determined by an IRC. The ALEX study demonstrated a significant improvement in PFS. The time to cause-specific CNS progression as assessed by IRC was also significantly improved; there was a lower incidence of progression in the CNS as the first site of disease progression, alone or with concurrent systemic progression, in the ALECENSA arm (12%) as compared to the crizotinib arm (45%). Efficacy results from ALEX are summarized in Table 7 and Figure 1.Table 7: Efficacy Results in ALEX per IRC AssessmentALECENSAN=152CrizotinibN=151CNS: central nervous system, ORR: overall response rate, IRC: independent review committee, CI: confidence interval, NE: not estimable. Progression-Free Survival   Number of events (%)63 (41%)92 (61%)    Progressive disease (%)51 (34%)82 (54%)    Death (%)12 (8%)10 (7%)  Median in months (95% CI)25.7 (19.9, NE)10.4 (7.7, 14.6)  Hazard ratio (95% CI) Stratified by race (Asian vs. non-Asian) and CNS metastases at baseline (yes vs. no) for Cox model, log-rank test and Cochran Mantel-Haenszel test, respectively 0.53 (0.38, 0.73)  P-value < 0.0001Overall Response Rate   Overall response rate, % (95% CI) Clopper and Pearson exact binomial 95% confidence interval.79% (72, 85)72% (64, 79)  P-value 0.1652  Complete response, %13%6%  Partial response, %66%66%Duration of Response   Number of respondersn=120n=109  Response duration ≥6 months82%57%  Response duration ≥12 months64%36%  Response duration ≥18 months37%14%Figure 1: Kaplan Meier Plot of Progression-Free Survival (IRC) in ALEX Results for PFS as determined by investigator assessment (HR=0.48 [95% CI: 0.35-0.66], stratified log-rank p<0.0001) were similar to that observed by IRC. At the data cutoff point overall survival data was not mature.The results of prespecified exploratory analyses of CNS response rate in patients with measurable CNS lesions at baseline are summarized in Table 8.Table 8: IRC-Assessed CNS Responses in Patients with Measurable CNS Lesions at Baseline in ALEXALECENSACrizotinibIRC: Independent Review Committee; CI: Confidence Interval; NE: Not EstimableCNS Tumor Response AssessmentN = 21N = 22CNS Objective Response Rate, % (95% CIClopper and Pearson exact binomial 95% confidence interval)81% (58, 95)50% (28,72)  Complete Response38%5%Duration of CNS Response  Number of responders1711  CNS response duration ≥ 12 months59%36%

ALK-Positive Metastatic NSCLC Previously Treated with CrizotinibThe safety and efficacy of ALECENSA were established in two single-arm, multicenter clinical trials: NP28761 (NCT01588028) and NP28673 (NCT01801111). Patients with locally advanced or metastatic ALK-positive NSCLC, who have progressed on crizotinib, with documented ALK-positive NSCLC based on an FDA-approved test, and ECOG PS of 0-2 were enrolled in both studies. Eligibility criteria permitted enrollment of patients with prior chemotherapy and prior CNS radiotherapy provided that CNS metastases were stable for at least two weeks. All patients received ALECENSA 600 mg orally twice daily. The major efficacy outcome measure in both studies was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) as evaluated per Independent Review Committee (IRC). Additional outcome measures as evaluated by the IRC included duration of response (DOR), CNS ORR, and CNS DOR.NP28761 was conducted in North America and enrolled 87 patients. Baseline demographic and disease characteristics in were median age 54 years old (range 29 to 79, 18% 65 and over), 84% White and 8% Asian, 55% female, 35% ECOG PS 0 and 55% ECOG PS 1, 100% never or former smokers, 99% Stage IV, 94% adenocarcinoma, and 74% prior chemotherapy. The most common sites of extra-thoracic metastasis included 60% CNS (of whom 65% had received CNS radiation), 43% lymph nodes, 36% bone, and 34% liver.NP28673 was conducted internationally and enrolled 138 patients. Baseline demographic and disease characteristics in NP28673 were median age 52 years old (range 22 to 79, 10% 65 and over), 67% White and 26% Asian, 56% female, 32% ECOG PS 0 and 59% ECOG PS 1, 98% never or former smokers, 99% Stage IV, 96% adenocarcinoma, and 80% prior chemotherapy. The most common sites of extra-thoracic metastasis included 61% CNS (of whom 73% had received CNS radiation), 51% bone, 38% lymph nodes, and 30% liver.Efficacy results from NP28761 and NP28673 in all treated patients are summarized in Table 9. The median duration of follow-up on Study NP28761 was 4.8 months for both IRC and Investigator assessments and on Study NP28673, 10.9 months for IRC assessment and 7.0 months for Investigator assessment. All responses were partial responses.Table 9: Efficacy Results in Studies NP28761 and NP28673 Efficacy ParameterNP28761 (N=87)NP28673 (N=138)IRC18 patients in NP28761 and 16 patients in NP28673 did not have measurable disease at baseline as per IRC assessment and were classified as non-responders in the IRC analysis. AssessmentInvestigator AssessmentIRC AssessmentInvestigator AssessmentObjective Response Rate (95% CI)38%(28; 49)46%(35; 57)44%(36; 53)48%(39; 57)Number of Responders33406166Duration of Response, median in months (95% CI)7.5(4.9, Not Estimable)NE(4.9, Not Estimable)11.2 (9.6, Not Estimable)7.8(7.4, 9.2)An assessment of ORR and duration of response for CNS metastases in the subgroup of 51 patients in NP28761 and NP28673 with baseline measurable lesions in the CNS according to RECIST v1.1 are summarized in Table 10. Thirty-five (69%) patients with measurable CNS lesions had received prior brain radiation, including 25 (49%) who completed radiation treatment at least 6 months before starting treatment with ALECENSA. Responses were observed irrespective of prior brain radiation status.Table 10: CNS Objective Response in Patients with Measurable CNS Lesions in Studies NP28761 and NP28673Efficacy ParameterN=51CNS Objective Response Rate (95% CI)61%(46, 74)  Complete Response18%  Partial Response43%CNS Duration of Response, median in months (95% CI)9.1(5.8, Not Estimable)

HepatotoxicityInform patients of the signs and symptoms of bilirubin and hepatic transaminase elevations. Advise patients to contact their healthcare provider immediately for signs or symptoms of bilirubin and hepatic transaminase elevations [see Warnings and Precautions (5.1)].

Interstitial Lung Disease (ILD)/PneumonitisInform patients of the risks of severe ILD/pneumonitis. Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions (5.2)].

Renal ImpairmentInform patients of the risk of severe and potentially fatal renal impairment. Advise patients to contact their health care provider for change in urine color, reduced urine output, or swelling in the legs and feet [see Warnings and Precautions (5.3)].

BradycardiaInform patients that symptoms of bradycardia including dizziness, lightheadedness, and syncope can occur while taking ALECENSA. Advise patients to contact their healthcare provider to report these symptoms and to inform their healthcare provider about the use of any heart or blood pressure medications [see Warnings and Precautions (5.4)].

Severe Myalgia/CPK elevationInform patients of signs and symptoms of myalgia, including unexplained and/or persistent muscle pain, tenderness, or weakness. Advise patients to contact their healthcare provider immediately to report new or worsening symptoms of muscle pain or weakness [see Warnings and Precautions (5.5)].

PhotosensitivityInform 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 study drug 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 [see Adverse Reactions (6.1)].

Embryo-Fetal ToxicityALECENSA can cause fetal harm if taken during pregnancy. Advise a pregnant woman of the potential risk to a fetus [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1, 8.3)].Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for at least 1 week after the last dose of ALECENSA. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1, 8.3)]. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months after the last dose [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

LactationAdvise women not to breastfeed during treatment with ALECENSA and for one week after the last dose [see Use in Specific Populations (8.2)].

AdministrationInstruct patients to take ALECENSA twice a day. Advise patients to take ALECENSA with food and to swallow ALECENSA capsules whole [see Dosage and Administration (2.2)].

Missed DoseAdvise patients that if a dose of ALECENSA is missed or if the patient vomits after taking a dose of ALECENSA, patients should be advised not to take an extra dose, but to take the next dose at the regular time [see Dosage and Administration (2.2)].

Distributed by:Genentech USA, Inc.A Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990ALECENSA® is a registered trademark ofChugai Pharmaceutical Co., Ltd., Tokyo, Japan©2017 Genentech, Inc. All rights reserved.

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

7 Drug Interactions

No pharmacokinetic interactions with alectinib requiring dosage adjustment have been identified [see Clinical Pharmacology (12.3)].

8.4 Pediatric Use

The safety and effectiveness of ALECENSA in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of ALECENSA did not include sufficient number of subjects aged 65 and older to determine whether they respond differently from younger subjects.

8.6 Renal Impairment

No dose adjustment is recommended for patients with mild or moderate renal impairment. The safety of ALECENSA in patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease has not been studied [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to upper limit of normal (ULN) and aspartate transaminase (AST) greater than ULN or total bilirubin greater than 1.0 to 1.5 times ULN and any AST). The safety of ALECENSA in patients with moderate or severe hepatic impairment has not been studied [see Clinical Pharmacology (12.3)].

10 Overdosage

No experience with overdose is available. There is no specific antidote for overdose with ALECENSA. Alectinib and its major active metabolite M4 are > 99% bound to plasma proteins; therefore, hemodialysis is likely to be ineffective in the treatment of overdose.

11 Description

ALECENSA (alectinib) is a kinase inhibitor for oral administration. The molecular formula for alectinib is C30H34N4O2 ∙ HCl. The molecular weight is 482.62 g/mol (free base form) and 519.08 g/mol (hydrochloride salt). Alectinib is described chemically as 9-ethyl-6, 6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6, 11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride. The chemical structure of alectinib is shown below: Alectinib HCl is a white to yellow white powder or powder with lumps with a pKa of 7.05 (base). ALECENSA is supplied as hard capsules containing 150 mg of alectinib (equivalent to 161.33 mg alectinib HCl) and the following inactive ingredients: lactose monohydrate, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate, and carboxymethylcellulose calcium. The capsule shell contains hypromellose, carrageenan, potassium chloride, titanium dioxide, corn starch, and carnauba wax. The printing ink contains red iron oxide (E172), yellow iron oxide (E172), FD&C Blue No. 2 aluminum lake (E132), carnauba wax, white shellac, and glyceryl monooleate.

12.1 Mechanism Of Action

Alectinib is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity.Alectinib and M4 demonstrated in vitro and in vivo activity against multiple mutant forms of the ALK enzyme, including some mutations identified in NSCLC tumors in patients who have progressed on crizotinib. In mouse models implanted with tumors carrying ALK fusions, administration of alectinib resulted in antitumor activity and prolonged survival, including in mouse models implanted intracranially with ALK-driven tumor cell lines.

12.3 Pharmacokinetics

The pharmacokinetics of alectinib and its major active metabolite M4 have been characterized in patients with ALK-positive NSCLC and healthy subjects. In patients with ALK-positive NSCLC, the geometric mean (coefficient of variation %) steady-state maximal concentration (Cmax,ss) for alectinib was 665 ng/mL (44%) and for M4 was 246 ng/mL (45%) with peak to trough concentration ratio of 1.2. The geometric mean steady-state area under the curve from 0 to 12 hours (AUC0-12h,ss) for alectinib was 7,430 ng*h/mL (46%) and for M4 was 2,810 ng*h/mL (46%). Alectinib exposure is dose proportional across the dose range of 460 mg to 900 mg (i.e., 0.75 to 1.5 times the approved recommended dosage) under fed conditions. Alectinib and M4 reached steady-state concentrations by day 7. The geometric mean accumulation was approximately 6-fold for both alectinib and M4.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity studies with alectinib have not been conducted.Alectinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay, but was positive with an increased number of micronuclei in a rat bone marrow micronucleus test. The mechanism of micronucleus induction was abnormal chromosome segregation (aneugenicity) and not a clastogenic effect on chromosomes. No studies in animals have been performed to evaluate the effect of alectinib on fertility. No adverse effects on male and female reproductive organs were observed in general toxicology studies conducted in rats and monkeys.

16 How Supplied/Storage And Handling

Hard capsules, white 150 mg capsules with "ALE" printed in black ink on the cap and "150 mg" printed in black ink on the body, available in:240 capsules per bottle:NDC 50242-130-01

Storage And Handling

Storage and stability: Do not store above 30°C (86°F). Store in the original container to protect from light and moisture.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).Inform patients of the following:

Spl Patient Package Insert

  • This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 11/2017    PATIENT INFORMATIONALECENSA® (a-le-sen-sah)(alectinib)capsulesWhat is the most important information I should know about ALECENSA?ALECENSA may cause serious side effects, including:Liver problems (hepatotoxicity). ALECENSA may cause liver injury. Your healthcare provider will do blood tests at least every 2 weeks for the first 3 months, and then 1 time each month and as needed during treatment with ALECENSA. Tell your healthcare provider right away if you get any of the following signs and symptoms:feeling tiredfeeling less hungry than usualyellowing of your skin or the whites of your eyesdark urineitchy skinnausea or vomitingpain on the right side of your stomach areableeding or bruising more easily than normalLung problems. ALECENSA may cause severe or life-threatening swelling (inflammation) of the lungs during treatment. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms, including trouble breathing, shortness of breath, cough, or fever.Kidney problems. ALECENSA may cause severe or life-threatening kidney problems. Tell your healthcare provider right away if you have a change in the amount or color of your urine, or if you get new or worsening swelling in your legs or feet.Slow heartbeat (bradycardia). ALECENSA may cause very slow heartbeats that can be severe. Your healthcare provider will check your heart rate and blood pressure during treatment with ALECENSA. Tell your healthcare provider right away if you feel dizzy, lightheaded, or if you faint during treatment with ALECENSA. Tell your healthcare provider if you take any heart or blood pressure medicines.Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with ALECENSA and can be severe. Your healthcare provider will do blood tests at least every 2 weeks for the first month and as needed during treatment with ALECENSA. Tell your healthcare provider right away if you get new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness. See "What are the possible side effects of ALECENSA?" for more information about side effects.What is ALECENSA?ALECENSA is a prescription medicine used to treat people with non-small cell lung cancer (NSCLC):that is caused by an abnormal anaplastic lymphoma kinase (ALK) gene, andthat has spread to other parts of your bodyIt is not known if ALECENSA is safe and effective in children.Before you take ALECENSA, tell your healthcare provider about all of your medical conditions, including if you:have liver problemshave lung or breathing problemshave a slow heartbeatare pregnant or plan to become pregnant. ALECENSA can harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with ALECENSA or think you may be pregnant.Females who are able to become pregnant should use effective birth control during treatment with ALECENSA and for 1 week after the final dose of ALECENSA.Males who have female partners that are able to become pregnant should use effective birth control during treatment with ALECENSA and for 3 months after the final dose of ALECENSA.are breastfeeding or plan to breastfeed. It is not known if ALECENSA passes into your breast milk. Do not breastfeed during treatment with ALECENSA and for 1 week after the final dose of ALECENSA. Talk to your healthcare provider about the best way to feed your baby during this time. Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements.How should I take ALECENSA?Take ALECENSA exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking ALECENSA unless your healthcare provider tells you to.Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with ALECENSA if you have side effects.Take ALECENSA 2 times a day. Take ALECENSA with food.Swallow ALECENSA capsules whole. Do not open or dissolve the capsule contents.If you miss a dose of ALECENSA, do not take the missed dose. Take your next dose at your regular time.If you vomit after taking a dose of ALECENSA, do not take an extra dose. Take your next dose at your regular time.What should I avoid while taking ALECENSA?Avoid spending time in the sunlight during treatment with ALECENSA and for 7 days after the final dose of ALECENSA. You may burn more easily and get severe sunburns. Use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.What are the possible side effects of ALECENSA?ALECENSA may cause serious side effects, including:See "What is the most important information I should know about ALECENSA?"The most common side effects of ALECENSA include:tirednessconstipationswelling in your hands, feet, ankles, face and eyelidsmuscle pain, tenderness, and weakness (myalgia). See "What is the most important information I should know about ALECENSA?"anemiaThese are not all of the possible side effects of ALECENSA. For more information, ask your healthcare provider or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store ALECENSA?Do not store ALECENSA at temperatures above 86°F (30°C).Store ALECENSA capsules in the original container.Keep ALECENSA capsules dry and away from light.Keep ALECENSA and all medicines out of the reach of children.General information about the safe and effective use of ALECENSA.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ALECENSA for a condition for which it was not prescribed. Do not give ALECENSA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about ALECENSA that is written for health professionals.What are the ingredients in ALECENSA?Active ingredient: alectinibInactive ingredients: lactose monohydrate, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate and carboxymethylcellulose calcium. Capsule shell contains: hypromellose, carrageenan, potassium chloride, titanium dioxide, corn starch, and carnauba wax. Printing ink contains: red iron oxide (E172), yellow iron oxide (E172), FD&C Blue No. 2 aluminum lake (E132), carnauba wax, white shellac, and glyceryl monooleate.Distributed by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990ALECENSA® is a registered trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan©2017 Genentech, Inc. For more information, go to www.ALECENSA.com or call 1-800-253-2367.

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