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ALECENSA(alectinib)capsules
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ALECENSA safely and effectively. See full prescribing information for ALECENSA.
ALECENSA ® (alectinib) capsules, for oral use
Initial U.S. Approval: 2015
INDICATIONS AND USAGE
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 trials. ( 1)
DOSAGE AND ADMINISTRATION
600 mg orally twice daily. Administer ALECENSA with food. ( 2.1)
DOSAGE FORMS AND STRENGTHS
Capsules: 150 mg ( 3)
CONTRAINDICATIONS
None. ( 4)
WARNINGS AND PRECAUTIONS
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Hepatotoxicity: Monitor liver laboratory tests every 2 weeks during the first 2 months of treatment, and then periodically during treatment. In case of severe ALT, AST, or bilirubin elevations, withhold, then reduce dose, or permanently discontinue ALECENSA. (2.2, 5.1)
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Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 0.4% of patients. Immediately withhold ALECENSA in patients diagnosed with ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis have been identified. (2.2, 5.2)
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Bradycardia: Monitor heart rate and blood pressure regularly. If symptomatic, withhold ALECENSA then reduce dose, or permanently discontinue. (2.2, 5.3)
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Severe Myalgia and Creatine Phosphokinase (CPK) Elevation: Occurred in 1.2% and 4.6% of patients, respectively. 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. (2.2, 5.4)
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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. (5.5, 8.1 8.3)
ADVERSE REACTIONS
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.
USE IN SPECIFIC POPULATIONS
Lactation: Do not breastfeed. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 12/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
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.
2 DOSAGE AND ADMINISTRATION
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.
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.
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
5 WARNINGS AND PRECAUTIONS
5.1 Hepatotoxicity
Elevations of AST greater than 5 times the upper limit of normal (ULN) occurred in 3.6% of patients, and elevations of ALT greater than 5 times the ULN occurred in 4.8% of patients. Elevations of bilirubin greater than 3 times the ULN occurred in 2.8% of patients. The majority (73% of the patients with hepatic transaminase elevations and 49% of the patients with bilirubin elevations) of these events occurred during the first 2 months of treatment. Four patients discontinued ALECENSA for Grade 3-4 AST and/or ALT elevations, and 3 patients discontinued ALECENSA for Grade 3 bilirubin elevations. Two patients with Grade 3-4 AST/ALT elevations had documented drug induced liver injury by liver biopsy.
Monitor liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 2 months of treatment, then periodically during treatment, 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 (2.2)].
5.2 Interstitial Lung Disease (ILD)/Pneumonitis
Severe ILD (Grade 3) occurred in one (0.4%) of 253 patients exposed to ALECENSA in clinical trials.
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 (2.2) and Adverse Reactions (6)].
5.3 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 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 eva luate 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 (2.2)].
5.4 Severe Myalgia and Creatine Phosphokinase (CPK) Elevation
Myalgia or musculoskeletal pain occurred in 29% of patients in Study 1 and Study 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 two 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 (2.2)].
5.5 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:
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 eva luated 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.
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.
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