Data from FDA (Food and Drug Administration, USA) - Curated by Toby Galbraith - Last updated 20 July 2017

Indication(s)

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) 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 [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ALECENSA is a kinase inhibitor 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 confirmatory trial. (1)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Breakthrough Cancer Pain Learning Zone

Invitation to watch the online broadcast of the BeCOn OWN event 'Shifting paradigms in BTcP management' on June 16 2017.

Visit Breakthrough Cancer Pain Learning Zone

Oral Anticoagulation Reversal

Experts discuss the use of non-vitamin K oral anticoagulants in the treatment and prevention of stroke, deep vein thrombosis and pulmonary embolism in atrial fibrillation patients.

Visit Oral Anticoagulation Reversal

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS None. None. (4)
Adverse reactions
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)] Bradycardia [see Warnings and Precautions (5.3)] Severe Myalgia and Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.4)] Embryo-Fetal Toxicity [see Warnings and Precautions (5.5)] The most common adverse reactions (incidence ≥20%) were fatigue, constipation, edema and myalgia. (6) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. The safety of ALECENSA was evaluated in 253 patients with ALK-positive non-small cell lung cancer (NSCLC) treated with ALECENSA 600 mg orally twice daily in two clinical trials, Studies 1 and 2. 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%). Table 3 summarizes adverse reactions in Studies 1 and 2. Table 3. Adverse Reactions in ≥ 10% (All Grades) or ≥ 2% (Grade 3-4) of Patients in Studies 1 and 2 Adverse Reactions ALECENSA N=253 All Grades (%) Grades 3-4 (%)Per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Fatigue Includes fatigue and asthenia. 41 1.2 Constipation 34 0 Edema Includes peripheral edema, edema, generalized edema, eyelid edema, and periorbital edema. 30 0.8 Myalgia Includes myalgia and musculoskeletal pain. 29 1.2 Cough 19 0 Rash Includes rash, maculopapular rash, acneiform dermatitis, erythema, generalized rash, papular rash, pruritic rash, and macular rash. 18 0.4 Nausea 18 0 Headache 17 0.8 Diarrhea 16 1.2 Dyspnea 16 3.6 Includes one Grade 5 event Back pain 12 0 Vomiting 12 0.4 Increased weight 11 0.4 Vision disorder Includes blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia. 10 0 Additional safety information from clinical trial experience Photosensitivity occurred in 9.9% of patients exposed to ALECENSA in Studies 1 and 2. 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 4 summarizes laboratory abnormalities of ALECENSA in Studies 1 and 2. Table 4. Laboratory Abnormalities Occurring in >20% of Patients in Studies 1 and 2 Parameter Alectinib N=250 All Grades (%) Grades 3-4 (%)Per CTCAE version 4.0 Chemistry Increased AST 51 3.6 Increased Alkaline Phosphatase 47 1.2 Increased CPK n=218 for CPK (with baseline values missing for 91 of these patients). 43 4.6 Hyperbilirubinemia 39 2.4 Hyperglycemian=152 for fasting blood glucose (with baseline values missing for 5 of these patients). 36 2.0 Increased ALT 34 4.8 Hypocalcemia 32 0.4 Hypokalemia 29 4.0 Increased Creatinine Only patients with creatinine increases based on ULN definition. 28 0 Hypophosphatemia 21 2.8 Hyponatremia 20 2.0 Hematology Anemia 56 2.0 Lymphopenia n=217 for lymphocytes (with baseline values missing for 5 of these patients). 22 4.6

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION 600 mg orally twice daily. Administer ALECENSA with food. (2.1) 2.1 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. 2.2 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 CriteriaALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase ALECENSA Dose Modification 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. 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 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.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Do not breastfeed. (8.2) 8.1 Pregnancy Risk Summary Based 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 Data In 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. 8.2 Lactation Risk Summary There are no data on the presence of alectinib or its metabolites in human milk, the effects of alectinib on the breast-fed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breast-fed infants from alectinib, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after the final dose. 8.3 Females and Males of Reproductive Potential Contraception Females 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 [see Use in Specific Populations (8.1)]. Males 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 [see Non Clinical Toxicology (13.1)]. 8.4 Pediatric Use The safety and effectiveness of ALECENSA in pediatric patients have not been established. Animal Data Juvenile 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. 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)].

Interactions

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

More information

Category Value
Authorisation number NDA208434
Agency product number P9YY73LO6J
Orphan designation No
Product NDC 50242-130
Date Last Revised 14-11-2016
Type HUMAN PRESCRIPTION DRUG
RXCUI 1727485
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.
Marketing authorisation holder Genentech, Inc.