You may also report side effects to Genentech at (888) 835-2555.
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.
Important Safety Information
Warnings and Precautions
Elevations of AST >5X the upper limit of normal (ULN) occurred in 4.6% of patients, and elevations of ALT >5X the ULN occurred in 5.3% of patients. Elevations of bilirubin >3X 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 ≥3X the ULN and total bilirubin ≥2X the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with ALECENSA across clinical trials. Three patients with Grades 3-4 AST/ALT elevations had drug-induced liver injury (2 documented by liver biopsy)
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
ILD/pneumonitis occurred in 3 (0.7%) patients treated with ALECENSA. 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 (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
Renal impairment occurred in 8% of patients. 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 ≤1.5X ULN, then resume at reduced dose
Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (8.6%) have been reported in patients treated with ALECENSA. Eighteen percent of 365 patients treated with ALECENSA for whom serial ECGs were available had heart rates of
Monitor heart rate and blood pressure regularly. Dose modification is not required in cases of asymptomatic bradycardia. In cases of symptomatic bradycardia that are 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 26% of patients. 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. 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
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 constipation (34%), fatigue (26%), edema (22%), myalgia (23%), and anemia (20%)
Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSA
Use in Specific Populations
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
Because of the potential for serious adverse reactions in breastfed 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
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.
Medical Professional Resources
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